Laccase, one of the metalloproteins, belongs to the multicopper oxidase family. It oxidizes a wide range of substrates and generates water as a sole by-product. The engineering of laccase is important to broaden their industrial and environmental applications. The general assumption is that the low redox potential of laccases is the principal obstacle, as evidenced by their low activity towards certain substrates. Therefore, the primary goal of engineering laccases is to improve their oxidation capability, thereby increasing their redox potential. Even though some of the determinants of laccase are known, it is still not entirely clear how to enhance its redox potential. However, the laccase active site has additional characteristics that regulate the enzymes’ activity and specificity. These include the electrostatic and hydrophobic environment of the substrate binding pocket, the steric effect at the substrate binding site, and the orientation of the binding substrate with respect to the T1 site of the laccase. In this review, these features of the substrate binding site will be discussed to highlight their importance as a target for future laccase engineering. T. versicolor, T. hirsuta, and all laccases have a high reduction potential range of about 780 mV vs. NHE [Cerrena maxima, Coriolopsis fulvocinerea, Trametes ochracea, and Trametes hirsuta. The direct redox titration method utilizing mediators was used to calculate the redox potential, which came in the range of 750 to 800 mV vs. NHE [0 +400 to +800 mV) as compared to other oxidoreductases such as peroxidases [Laccases  are metalloenzymes that are members of the multicopper oxidase family and are characteristically extracellular monomeric glycoproteins ,5,6. The vs. NHE ,20. The  vs. NHE . Olbrich vs. NHE . It has oxidases ,25,26. Hoxidases ,29,30,31oxidases ,33. Laccoxidases ,35. The oxidases . This lecat/Km) is influenced by the redox potential of the T1 copper site [Laccases exhibit a peculiar fold that consists of three cupredoxin domains, and their active site consists of four copper atoms. These atoms are categorized as type 1 copper (T1Cu) in the T1 site (mononuclear copper center) and a cluster of type 2 and type 3 coppers  in the T2/T3 site (trinuclear copper center) as shown in the per site ,41. Monoper site ,43. The per site ,35.The T1Cu atom is coordinated by the side chains of one cysteine residue and two histidine residues. The Cu atom and the atoms taking part in its coordination fall in the same plane, while on both sides, side chains of the axial hydrophobic residues are present  Figure .The highly conserved residue isoleucine is situated on one side of T1Cu, while phenylalanine, methionine, or leucine residues could be situated in the opposite direction in all the three-domain laccases that are structurally characterized. The lowest redox potential is of those laccases that contain methionine in their axial position ,46,47.The T2/T3 site consists of three Cu atoms  and eight coordinating histidine residues. The T2Cu atom is coordinated by two histidine residues, and it can be additionally linked by one or two oxygen ligands. This results in the development of a square-planar structure. The T3Cu and T3’Cu atoms are coordinated by six histidine residues. These are coordinated with each other through the oxygen as a ligand shown in The mononuclear T1 site is where the oxidation of the substrate occurs. The electrons are then transferred to the two histidine residues along a cysteine-coordinating T1Cu.The trinuclear site, where the reduction of dioxygen occurs, contains T3 coppers that coordinate with these histidine residues ,50. The cat and increase in Km but no change in the redox potential of T1Cu was observed in Rhizoctonia solani (E0 = +710 mV) and Myceliophthora thermophila (E0 = +470 mV) laccase substrate binding pockets with a triple mutation of a tripeptide . The observed changes in substrate docking were attributed to steric and electrostatic hindrances introduced upon mutation [2 and –OH groups are towed inward by the negative charge of this deprotonated carboxylate group and directed to the histidine ligand (H458). During the transfer of electrons to T1Cu through the histidine ligand, the aspartate residue helps in the deprotonation of the substrate. This provides a coordinated electron/proton transfer during the oxidation of phenolic compounds [It was first shown by Xu and co-workers that the characteristics of the enzyme pocket determine substrate binding and electron transfer. During the process of substrate oxidation, the presence of an electrostatic environment within the active site of laccase is beneficial to the coordinated transfer of electrons and protons. A significant drop in kmutation . Later omutation . In factmutation . The carompounds . Monza eompounds . The recompounds .A recent study using molecular dynamic simulation demonstrated that electrostatic interactions were the primary forces involved between coniferyl alcohol and laccase. The strong electrostatic interaction of L112 is because of the carboxyl group’s electropositive carbon atom, which is able to electrostatically draw the coniferyl alcohol-attached phenolic hydroxyl group’s negatively charged oxygen atom .Trametes villosa (E0 = +790 mV) and Myceliophthora thermophila (E0 = +470 mV). Even though ∆G0 between the substrate and T1 Cu site is a rate-determining reaction step, the results of the investigation show that some of the substituted anilines and phenols did not get oxidized by the enzyme even if they had suitable redox potential. A description was made relating the substrate consumption to the maximum dimension of substituted phenols. Hydrophobic residues  delimit one of the binding pocket’s sides, while other residues  are part of the opposite wall. Occupied by the two phenylalanine residues (F332 and F265), which are separated by a distance of 10.8 Å forces involved in interactions between substrate and active site residues of the laccase  form the entrance path of the substrate. A few putative substrates were found to be recalcitrant towards oxidation by Trametes versicolor laccase (TvL). The sterically burdened 2,4,6-tri(But)phenol, which measures 11.8 Å  and 10.5 Å long, had not been oxidized. However, 4-(but)phenol and also 2,4,6-trimethylphenol, which are bulkier but less wide (9.1 Å) than 2,4,6-tri(but)phenol, were completely oxidized [Steric hindrance can also be an activity-determining factor, as bulky substrates may find it difficult to bind at the substrate binding pocket lined by residues with large side chains ,59. Tadeoxidized . Moldes oxidized .Another very good example supporting steric hindrance as an activity-determining factor was demonstrated by Galli and co-workers. A site-directed mutagenesis strategy was used in TvL to examine how the substitution of the hydrophobic and bulky phenylalanine residues located at the prime positions at the T1 Cu site with small apolar residues that are less hindered, such as alanine, could probably expedite the access of large substrates while simultaneously preserving the non-polar feature of the active site. Oxidation of thymol by wild-type (WT), F162A, and F332A mutants was found to be similar, whereas F265A was comparatively less efficient. The extent of oxidation of thymol by WT and mutants (F162A and F332A) was anticipated to be similar due to the smaller size of the substrate. It has a width of 7.7 Å, which is smaller than the distance of 10.8 Å between the two phenylalanines, F332 and F265, in TvL, which define the entry to the enzyme’s active site. Hence, the alterations done to enlarge the width of the binding pocket entrance should not affect the activity of the mutants (F162A and F332A). While, for the oxidation of 3,5-di-t-bu-phenol, the efficiency of F332A appeared similar to that of WT, F162A exhibited a higher conversion rate as compared to WT, and F265A again showed a lower conversion rate. Docking simulations rationalized the results by showing that F332 is far away from the substrate and does not interact with it; therefore, the F332A mutation did not result in any change in the reactivity. On the other hand, F162 interacts with the substrate and restrains the entrance; hence, the oxidative reactivity of the F162A mutant was mainly due to the increased nearness of the substrate to H458 (one of the T1 Cu ligands) that resulted from relaxation in steric hindrance upon switching of phenylalanine to alanine. Finally, it was observed that F265 is quite far from the active site; therefore, the lowered activity of the F265A mutant is probably due to the disruption of hydrophobic forces between the alanine and the potential substrate [In another study of conformations of the substrate at the active site by docking, it was shown that the bulky planar ring structure of the residues in the catalytic site of laccase creates steric hindrance due to which the substrate finds it difficult to enter the catalytic site of the enzyme . HoweverStreptomyces coelicolor resulted in improved kcat (fourfold increase) and Km (tenfold lower), which consequently resulted in around a 40-fold improvement in kcat/Km over the WT enzyme. It can be envisioned that substituting the methionine containing the long side chains with smaller residues will increase accessibility to the active site and reduce the distance between the T1Cu site and substrate, therefore enabling the transfer of electrons and enhancing the reaction rate [Myceliophthora thermophila laccase  and Pycnoporus cinnabarinus laccase  using computational tools. It has been shown earlier that MtL expresses improved kinetics over PcL for the oxidation of syringaldazine in spite of its low redox potential compared to PcL. This was understood by simulations performed to find out the most favorable binding modes of syringaldazine with both laccases. The results showed that binding is more favorable in MtL than PcL, and this favorable binding in MtL was due to the variations in the T1 site. A big loop containing residues 445 to 468, having N454, is present in MtL and holds the substrate in the orientation seen in Trametes versicolor laccase. Despite the substrate similarity, the biotransformation varied greatly. The chemical groups of the phenol ring affect the conformation and orientation of the substrate in the active site. Substrates with the phenol ring, which consist of two groups such as methyl ferulate and methyl caffeate, formed additional Hydrogen bonds with some residues in Trametes versicolor laccase–ligand complexes. As a result of the stable complexes, methyl ferulate and methyl caffeate were unable to be transformed [The crucial element affecting how quickly the substrate oxidizes is the substrate’s orientation in the laccase’s substrate binding pocket. Various site-directed mutagenesis studies have been conducted, which support the importance of the substrate’s orientation in the binding site. Substitution of V148L has resulted in an increased activity of mutant laccase compared to the parental enzyme. The presence of the aromatic ring of Y208 in the vicinity of the leucine side chain may have changed the loop (204–208) conformation at the substrate binding site containing the conserved D205, which interacts with the binding substrate. Conformational changes may have resulted in a favorable orientation of D205 towards the binding substrate, which has increased the reducing substrate’s oxidation, thus increasing the activity of the mutant . Mutatioion rate . Xie et ion rate . The cation rate . Lucas ansformed .Bacillus subtilis CotA-laccase were also reported to be responsible for increased enzyme activity [Bacillus pumilus CotA-laccase for the decolorization of dyes was enhanced due to increased hydrophobic interactions between the redox mediator 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and the catalytic residues [Thermus thermophilus SG0.5JP17 laccase (lacTT) identifies the substrate as having its side chain oriented towards the substrate entrance. As a result, it was hypothesized that replacing Lys with hydrophobic residues (M428 and L428) might change the conformation of loop 5, whereas replacing Lys with hydrophilic residues (R428 and E428) might not. The K428M mutation, consisting of lacTT, decolorized dye significantly better than the wild type [The hydrophobic milieu of the substrate-binding pocket also plays a crucial role in determining the activity of the laccase . The hydactivity . Chen etactivity . The actresidues . It was residues ,78. The residues . Recentlresidues . In a reresidues . The Lysild type .Engineering laccases is of great interest because of their broad range of functions, including industrial and environmental applications. Therefore, the number of laccases has been engineered to increase/enhance their activity and selectivity. But engineering the enzymes with rational methods has always been an appealing approach to saving time and effort. The most logical point that is usually considered for the rational engineering of laccase is to increase the redox potential of T1Cu at the active site. However, increasing the redox potential is a difficult task, as knowledge about increasing the redox potential of T1Cu effectively is still in its infancy. However, there are some other determinants at the active site of laccase that control its activity and can be engineered efficiently . The ele


To examined the efficacy and safety of Peng’s Shengjing recipe in treating asthenospermia with deficiency and failure of kidney yang. The traditional Chinese medicine (TCM) Peng’s Shengjing recipe might have benefits in treating male asthenospermia.This randomized, positive drug-controlled, single-blind pilot study enrolled outpatients from the Third Department of Traditional Chinese Medicine Surgery, Shanghai University of Traditional Chinese Medicine, Shanghai, China, between April 2020 and September 2020. A total of 99 participants were randomized to Shengjing recipe (n=50) and Xuanju capsule (n=49). They were treated for 12 weeks. The primary endpoint was routine semen examinations, including the percentage of sperm motility rated grade A, A+B, and A+B+C, and the clinical effective rate. The secondary endpoints were the levels of gonadotropins.p=0.030) and A+B grade sperms  were higher in the Shengjing recipe group than the Xuanju capsule group. The effective rates were 68% and 53.1% in the Shengjing recipe and Xuanju capsule groups (p=0.128). No safety signals were observed.The A grade sperms (18.9% versus [vs.] 13.9%, Peng’s Shengjing recipe improves the quality of sperms and is effective in treating clinical asthenospermia of deficiency of kidney yang. The treatment was well tolerated, without obvious hepatorenal toxicity.Chinese Clinical Research Registry No.: ChiCTR2000030845 The worldwide incidence of infertility for reproductive-aged couples is approximately 15%. In the United States, male factor infertility may affect approximately 9% of men aged 15-44. Male factors alone are involved in approximately 30% of infertile couples. In Western countries, the interventions for managing male infertility mainly aim to improve semen quality. The interventions included changes in lifestyle habits , antioxidant supplementation, hormones or antihormones to correct hormonal imbalances, varicocele repair, and sperm retrieval for in vitro fertilization. Still, these methods cannot achieve fertility in all patients. In China, Liu et al and Huang et al showed that semen quality declined in sperm donors in the past 2 decades. Male infertility corresponds to the category of “childless, cold sperm, seed, and not male” in traditional Chinese medicine (TCM). If kidney yang is insufficient, the kidney loses warmth, semen becomes thin, the sperm count decreases, and the sperm activity is low, resulting in asthenospermia. Therefore, the TCM treatment of male infertility should focus on warming and tonifying kidney yang, enriching kidney essence, and fully stimulating the vitality of semen.Asthenospermia refers to decreased sperm count and motility. The above drugs were used together to enhance the effect of sperm production. Sun et al showed that Peng’s Shengjing recipe could improve the parameters of asthenospermia. Basic experiments suggested that this effect might be related to the up-regulation of gonadotropins, including follicular-stimulating hormone (FSH) and testosterone (T). Research is necessary to determine the benefits of Peng’s Shengjing recipe in treating male asthenospermia.Peng’s Shengjing recipe is mainly composed of the Mantis Egg-case, hive, rigid silkworm, burnt astragalus, codonopsis, atractylodes, rehmannia, cornus, and Yizhiren.Therefore, this study aimed to examine the effectiveness and safety of Peng’s Shengjing recipe in the treatment of male asthenospermia with kidney yang deficiency. The results could help provide more treatment options for asthenospermia patients with kidney yang deficiency.The related studies on the subject was found through a search in PubMed, Embase, the Cochrane Library, and CKNI. Google was used to search the grey literature.This randomized, positive drug-controlled, single-blind pilot study enrolled outpatients from the Third Department of Traditional Chinese Medicine Surgery, Shanghai University of Traditional Chinese Medicine, Shanghai, China, between April and September 2020. The study was approved by the Ethics Committee of the Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai, China . All patients provided written informed consent before any study procedure. The work was carried out in accordance with the Institutional Review Board and carried out with the ethical standards set forth in the 1975 Helsinki Declaration. iii) met the classification standards of TCM for male infertility; iv) voluntarily participation; and v) no use of drugs related to male infertility within 30 days before treatment. The exclusion criteria were: i) azoospermia; ii) those with retrograde sperm drainage; iii) taking anti-epileptic or anti-tumor drugs that hinder sperm production and sperm motility; iv) congenital malformations, obstruction of the spermatic pathway, or testicular atrophy; v) immune infertility or varicocele; vi) orchitis; vii) epididymitis; viii) moderate and severe prostatitis; ix) genital surgery history; x) history of trauma that might affect fertility; xi) cardiovascular, liver, kidney, hematopoietic system, endocrine, immune, or genetic diseases; or xii) patients with mental diseases.The inclusion criteria were: i) 23-40 (inclusive) year-old male patient; ii) diagnosed with male infertility according to the diagnostic criteria of Western medicine;Asthenospermia due to kidney yang deficiency syndrome was defined as a loss of libido, low sperm count, low survival rate, weak motility, or poor ejaculation. The waist and knees are sore, tired, and weak, and the urine is long and clear. The tongue is pale, the coating is thin and white, and the pulse is heavy and thin.The dropout criteria were: i) participants with poor compliance  and ii) participants with serious adverse events (SAEs) during the study treatment.The randomization sequence was prepared by a third-party statistician using a random number table and in the form of sealed sequential envelopes. The patient received the indicated treatment according to the opened envelopes. Only the patients were blind to grouping.Peng’s Shengjing recipe was prepared using 18 grams (g) of Mantis egg case, 18 g of honeycomb, 18 g of rigid silkworm, 9 g of roasted astragalus, 9 g of codonopsis, 15 g of atractylodes, 15 g of rehmannia, 15 g of cornus, and 9 g of Yizhiren. The participants had to take 200 ml orally twice a day. A course of treatment was 12 weeks.The control group received the compound Xuanju capsule  3 times a day, 3 capsules each time, orally. Previous studies showed that Xuanju capsules could increase sperm density, sperm motility, and sperm activity and reduce the rate of sperm deformity without obvious adverse events.The percentage of sperms rated grade A, A+B, and A+B+C, semen volume, and efficacy were recorded by routine semen examinations. Each semen collection was carried out by masturbation after 3-5 days of abstinence. Semen quality was evaluated using computer-aided, fully automatic semen analysis (CASA) technology. The items included sperm motility and other parameters according to international standards.Treatment efficacy was rated as 1-markedly effective , 2-effective , or 3-invalid  / total number of people treated × 100%. The levels of gonadotropins  in the 2 groups were recorded before and after treatment. The primary endpoint was the results of routine semen examinations, including the percentage of sperm motility rated grade A, A+B, and A+B+C. The secondary endpoints were the clinical effective rate and the levels of gonadotropins . The safety assessment indexes , and aspartate transaminase (AST) were examined before and after treatment. The participants were followed up for 3 months after treatment by an attending surgeon with 10 years of experience in male infertility.According to the World Health Organization (WHO) criteria, asthenospermia was defined as sperm motility rated <25% for class A or rated <50% for class A+B.According to preliminary data, the clinical effective rate of Peng’s Shengjing recipe was approximately 60%, while the clinical effective rate of Fufang Xuanju capsule was approximately 40%. Therefore, the number of cases in each observation group was set as 30 cases/60%=50 cases.P-values of <0.05 were deemed statistically significant.The data were analyzed using the Statsitical Package for the Social Sciences, version 16.0 . The continuous variables with a normal distribution were presented as means ± standard deviations and analyzed using the independent-samples t-test (2-group comparisons). Otherwise, they were presented as medians (ranges) and analyzed using the Mann-Whitney U test. Continuous data from repeated measurements were statistically analyzed using repeated measurements analysis of variance. Categorical data were presented as numbers and precentages (%); they were analyzed using the Chi-square test. p>0.05), but the Shengjing recipe group had lower proportions of A+B grade sperms , lower LH levels , and lower ALT levels .A total of 123 outpatients were enrolled in this study from April to September 2020. Twenty-three participants were excluded due to complicated prostatitis (n=17) or varicocele (n=6). Therefore, 100 participants were randomized to Shengjing recipe (n=50) and Xuanju capsule . The proportion of grade A and A+B sperms were higher in the Shengjing recipe group than in controls . The effective rates were 68% and 53.1% in the Shengjing recipe and control groups (p=0.128)  had improved  .p<0.001), LH , and testosterone  increased after the intervention. The FSH  and testosterone  were higher in the Shengjing recipe group compared with the control group. Time×group interactions were observed for LH (Ptime×group=0.019) and testosterone (ptime×group<0.001) but not for FSH (ptime×group=0.752)  .p>0.05). The Peng’s Shengjing recipe group showed lower ALT  and AST  levels than the control group  were not significantly different between the 2 groups . Various TCM preparations strengthen the kidney and help yang use stiff silkworm, roasted astragalus, codonopsis, and cooked rehmannia as adjuvant drugs. Among them, stiff silkworm dispels wind and relieves spasms, resolves phlegm, and dispels congestion. Roasted astragalus and codonopsis have the functions of nourishing Qi and strengthening the kidney and spleen. Cooked rehmannia nourishes the blood and yin and fills the essence and marrow. Atractylodes macrocephala, common macrocarpium fruit, and Fructus alpiniae oxyphyllae are used as adjuvants. Atractylodes macrocephala invigorates the spleen and replenishes Qi. Common macrocarpium fruit tonifies the liver and kidney, astringes essence, and stops sweating. Fructus alpiniae oxyphyllae warms the kidney and consolidates the essence. The above drugs were used together to enhance the effect of sperm production.In Peng’s Shengjing recipe, the mantis egg case consolidates the essence and reduces urine, strengthens the kidney yang but not the heat, replenishes Qi and blood without affecting the diaphragm, and has the function of adjusting the dysfunction of multiple organs. Shengjing recipe also improved grade A and A+B sperms, and to a greater extent than in the Xuanju capsule group. These results are supported by Sun et al, who showed improvements in sperm motility, concentration, and morphology after 12 weeks of treatment with Shengjing recipe in patients with oligoasthenospermia. Yang et al showed that Shengjing recipe could improve sperm density and motility, and increase the pregnancy rate. Similar results were observed by Song et al, Guo et al, Zhang et al, and Chen et al.In the present study, Xuanju capsule, a classical TCM for male infertility, was used as positive control and showed improvements in grade A and A+B sperms. Yang et al showed that Shengjing recipe increased the production of nitric oxide in the rat testicles leading to an enhanced anti-oxidation power that is protective for the sperm. In addition, Shengjing recipe upregulates integrin α6/β1 expression through the PI3K/AKT pathway. Integrin α6/β1 is a determinant of sperm function.These effects are also supported by animal studies that shed some light on the mechanisms of Shengjing recipe. Indeed, animal studies reported increased sperm quality and quantity when treated with the Shengjing recipe, including animal models of drug-induced asthenospermia. showed that Shengjing recipe could increase FSH and T levels. Chen et al showed that Shengjing recipe could increase FSH, LH, and T.In the present study, Shengjing recipe increased the levels of FSH and T, but the exact clinical significance of these changes is unknown since the values were within the normal values at baseline and after treatment. Still, these changes were also observed in previous studies. Sun et al The Shengjing recipe group had lower ALT and LH levels at baseline compared with the control group, but these differences disappeared after 12 weeks of treatment, and the ALT levels of all patients remained within the limits of normal. Hence, these results suggest that Peng’s Shengjing recipe is safe.This study did not identify any safety signals using the Shengjing recipe. The kidney and liver parameters remained in the normal range. No obvious hepatorenal toxicity was recorded. This observation is supported by other studies of Shengjing recipe.The study population was relatively small, but it complied with the initial power calculation. No placebo control group was included, preventing the observation of the absolute effect of the Shengjing recipe. The effect could only be observed relative to Xuanju capsule. An untreated group could not be included for ethical reasons because asthenospermia is a treatable condition using TCM and because all included participants were seeking fertility treatments. The pregnancy outcomes were not evaluated, but the present study was not powered to do so. The blood and semen parameters were limited, impairing a complete analysis of the beneficial effects of the Shengjing recipe. In TCM clinical practice, sperm concentration and normal sperm form are closely related to the traditional concept of “body fluid”. In addition, sperm viability and hormone levels in this study are related to the TCM concept of “kidney yang”, and the Chinese medicine prescription selected in this study was mainly for the treatment of patients with kidney yang deficiency. Therefore, sperm concentration and normal sperm morphology were not included in the observation indicators. Additional studies are necessary.In conclusion, Peng’s Shengjing recipe improves the quality of sperm and shows effectiveness in patients with clinical asthenospermia due to kidney yang deficiency. The treatment was well tolerated, without obvious hepatorenal toxicity.


LKMS inhibited CYP2B6 in a mixed way, with Ki values of 59.44 μM. A phenotyping study based on an inhibition assay indicated that CYP2D6 contributes to the biotransformation of LKMS. A mixed inhibition of CYP2D6 with Ki values of 64.87 μM was also observed. Given that this study was performed in vitro, further in vivo studies should be conducted to identify the interaction between LKMS and canine CYP450 enzymes to provide data support for the clinical application of LKMS and the avoidance of adverse interactions between other drugs.Lekethromycin (LKMS) is a synthetic macrolide compound derivative intended for use as a veterinary medicine. Since there have been no in vitro studies evaluating its potential for drug–drug interactions related to cytochrome P450 (CYP450) enzymes, the effect of the inhibitory mechanisms of LKMS on CYP450 enzymes is still unclear. Thus, this study aimed to evaluate the inhibitory effects of LKMS on dog CYP450 enzymes. A cocktail approach using ultra-performance liquid chromatography–tandem mass spectrometry was conducted to investigate the inhibitory effect of LKMS on canine CYP450 enzymes. Typical probe substrates of phenacetin, coumarin, bupropion, tolbutamide, dextromethorphan, chlorzoxazone, and testosterone were used for CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4, respectively. This study showed that LKMS might not be a time-dependent inhibitor. LKMS inhibited CYP2A6, CYP2B6, and CYP2D6 via mixed inhibition. LKMS exhibited mixed-type inhibition against the activity of CYP2A6 with an inhibition constant (K Given the high research and development costs, long development process, and high failure rate of new drugs, the related problems of drug–drug interactions (DDIs) should be solved. Lekethromycin (LKMS), a derivative synthetic novel macrolide compound, has been used in veterinary medicine to treat respiratory disease. Pharmacokinetic and distribution studies have been completed on healthy and infected rats with different administration methods and doses, respectively ,2,3, sugOur study focused on the in vitro interactions of hepatic microsomal methods. Cytochrome P450 enzyme (CYP450) is a metabolic enzyme that participates in more than 90% of reported enzymatic reactions ,11,12,13Macrolide antibiotics have been widely used on livestock. The effect of macrolides on CYP450 can contribute to DDIs, such as erythromycin and its precursor drugs, which have been shown to inhibit the CYP3A4 enzyme, reducing the clearance of other drugs catalyzed by the CYP3A4 enzyme ,21,22,2350) to study the inhibitory effect of a drug on the CYP450 enzyme, the possibility of drug interaction with other drugs can be calculated theoretically, which can be predicted by creating a simple in vitro model [In the early stage of drug development, when measuring the in vitro half-maximal inhibitory concentration . The accuracy and precision are shown in A rapid and highly sensitive method was validated for the quantification of probe substrates in dog liver microsomes (DLMs) following the guidelines for bioanalytical method validation . The acem (Michaelis–Menten constant) values were 5.39 μM for PH, 0.41 μM for CAN, 9.15 μM for BP, 10.76 μM for TBD, 6.33 μM for DEX, 17.42 μM for CLN, and 85.21 μM for TS. For CAN, the Km was 2.0–4.3 μM in dog liver microsomes, and the value was 0.41 μM in this study [m for CLN was 17.42 μM, which was smaller compared with 42–82 μM in dog liver microsomes, but it was similar to the 25–37 μM in mini-pig liver microsomes [m for TS was 192 μM in dog liver microsomes, but the value was similar to the rat and mini-pig values of 84 μM and 79 μM, respectively [max  values were 0.22 nmol/min/mg protein for PH, 0.034 nmol/min/mg protein for CAN, 1.43 nmol/min/mg protein for BP, 293.1 nmol/min/mg protein for TBD, 6.16 nmol/min/mg protein for DEX, 5.4 nmol/min/mg protein for CLN, and 1.49 nmol/min/mg protein for TS. In contrast, the Vmax values for CAN, CLN, and TS were 1488–1656 pmol/min/mg/microsomal protein, 573–1129 pmol/min/mg/microsomal protein, and 68–180 pmol/min/mg/microsomal protein in dog liver microsomes [m for PH, TBD, and DEX ranged from 10–50 μM, 100–200 μM, and 2–10 μM in in vitro drug metabolism studies [It is important to use the right probe substrates, and the most common in vitro probes include phenacetin (PH) for CYP1A2, coumarin (CAN) for CYP2A6, bupropion (BP) for CYP2B6, tolbutamide (TBD) for CYP2C9, dextromethorphan (DEX) for CYP2D6, chlorzoxazone (CLN) for CYP2E1, and testosterone (TS) for CYP3A4 ,45,46,47is study . The Km crosomes . The Km ectively . Our fin50 values only preliminarily indicate the CYP450 enzyme inhibitory potential in the xenobiotics. In the presence of LKMS, as shown in 50 value of 39.66 μM. A similar inhibitory effect and concentration-dependent effect was observed in the activities of CYP2A6 (IC50 = 62.53 μM) and CYP2B6 (IC50 = 83.29 μM), while the IC50 values of CYP1A2, CYP2C9, CYP2E1, and CYP3A4 were >200 μM. LKMS slightly inhibited the activities of CYP2A6, CYP2B6, and CYP2D6, whereas it had no effect on the biotransformation activity of CYP1A2, CYP2C9, CYP2E1, or CYP3A4 in DLM. DDI-involved macrolides are attributed to mechanism-based CYP3A4, where macrolides inactivated HTS in liver microsomes [50 values lower than 100 μM [i of 135.6 μΜ. LKMS inhibited CYP2B6 and CYP2D6 in a mixed way with Ki values of 59.44 μM and 64.87 μM, respectively. The mixed inhibition was evident such that the alpha inhibition constants (αKi) for CYP2A6, CYP2D6, and CYP2B6 were 227.6, 279.6, and 12.07 μM (Ki ≠ αKi), respectively [Direct ICcrosomes . Macrolicrosomes . In addin 100 μM . The enz50 shift value is widely used to determine time-dependent inhibitions (irreversible inhibition) [50 fold-shift (the ratio of the IC50 absence of NADPH divided by the IC50 presence of NADPH) of CYP2B6 was <1, indicating a right shift, while that of CYP2A6 and CYP2D6 was a left shift [50 fold-shift values were <1.5 [The ICibition) . Accordift shift . The IC5ere <1.5 , which iAn inhibition assay was performed on DLMs to confirm the contribution of the identified CYP450 enzymes in the metabolism of LKMS. The inhibitors used included α-Naphthoflavone (CYP1A2), pilocarpine (CYP2A6), thiotepa (CYP2B6), sulfaphenazole (CYP2C9), quinidine (CYP2D6), sodium diethyldithiocarbamate (CYP2E1), and ketoconazole (CYP3A4). The percentage inhibition of the LKMS disappearance rate in DLMs is presented in Given the wide involvement of CYP450 in the metabolism processes of various drugs, the changes in the activity of hepatic metabolic enzymes may cause DDIs . Accurat50 values of LKMS regarding CYP450 isoforms, were determined. The results indicated that LKMS is a potent inhibitor of CYP2A6, CYP2B6, and CYP2D6 with IC50 values of 62.53 μΜ, 83.29 μΜ, and 39.66 μΜ, respectively, but it did not exhibit the inhibition of CYP1A2, CYP2C9, CYP2E1, or CYP3A4 activities, as indicated by IC50 values exceeding 200 μΜ. Moreover, LKMS exhibited the mixed inhibition of CYP2A6, CYP2B6, and CYP2D6 activities. Of these CYP450 isoforms, LKMS showed the most potent inhibition of CYP2D6. As reported, the variation in CYP2D enzyme activity can increase the risk of adverse drug reactions [50 shift assay is one of the effective means of assessing the time-dependent inhibition of CYP450 enzymes [50 fold-shifts of CYP2A6 and CYP2D6 were >1, while that of CYP2B6 was <1. Some drugs can be metabolized during preincubation to recover enzyme activity, resulting in an increased IC50 value [50 values depend on the choice of inhibitor concentrations to the extent of reversible inhibition and incubation time [i are more important, particularly in applying extrapolation to in vivo DDIs [i value of 135.6 μΜ. Additionally, LKMS inhibited CYP2D6 and CYP2B6 in a mixed manner, with Ki values of 64.87 μM and 59.44 μM, respectively. Macrolide veterinary medicines are composed of lactone rings, which differ in their abilities to bind to and inhibit CYP3A4 [50 of erythromycin in CYP1A2, CYP2C9, CYP2C19, and CYP2D6 was greater than 300 μM, which indicates a weak inhibitory effect on CYP450 [Furthermore, the inhibitory effects of LKMS on CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4, herein the IC enzymes . IC50 fo50 value ,64. Berrion time . Thus, tivo DDIs . In our t CYP3A4 ,68. Azitt CYP3A4 ,69. Togat CYP3A4 . Given tt CYP3A4 . In addit CYP3A4 . Similarn CYP450 . The phen CYP450 ,72. TherLKMS was provided by Henan Pulike Biological Engineering Co., Ltd. . LC-MS-grade methanol (MeOH), acetonitrile (ACN), and formic acid (FA) were purchased from Fisher Scientific . Ultrapure water was purified using a Milli-Q system . The following compounds were purchased from Sigma-Aldrich : PH, CAN, BP, TBD, DEX, CLN, and TS. ACE, HCAN, HBP, HTBD, HDEX, HCLN, and HTS were purchased from Beijing Huizhi Taikang Biological Technology . α-Naphthoflavone, Pilocarpine, Ticlopidine, Sulfaphenazole, Quinidine, sodium diethyldithiocarbamate, and Ketoconazole were purchased from Sigma . Phosphate buffer (PBS) tablets were purchased from Beijing Solarbio Technology . β-nicotinamide adenine dinucleotide phosphate was purchased from Fisher Scientific .PH, CAN, BP, TBD, DEX, CLN, and TS stock solutions were prepared in ACN at 10 mg/mL. Stock solutions of ACE, HCAN, HBP, HTBD, HDEX, HCLN, and HTS were prepared in MeOH at a concentration of 10 μg/mL. The internal standard of aflatoxin B1 was prepared at 200 ng/mL in ACN. The specific probe substrates, metabolites, and inhibitors are presented in 2O (A): ACN (B)  at a flow rate of 0.2 mL/min. The gradient was as follows: 0–1.0 min , 1.0–3.0 min , 3.0–4.0 min , 4.0–4.5 min , 4.6–6.0 min . The mass spectrometry parameters are provided in Quantitative analysis was carried out using UPLC coupled with TSQ Quantis™ . A HSS T3 column   was used at 35 °C. Both positive and negative electrospray ionization (ESI+ and ESI-) modes were used in this study. The other parameters were as follows: capillary voltage, 3.5 kV (ESI+) and 2.7kV (ESI−); ion source temperature, 320 °C; vaporizer temperature, 350 °C; sheath gas flow rate, 50 arb; and collision gas flow rate, 12 arb. An injection volume of 5 µL was applied. Analytes were eluted using a mobile phase of 0.1% FA·Hv/v) [The CYP450 enzymatic activities were characterized by their probe substrate reactions. Incubation mixtures were prepared in a total volume of 200 μL, which consisted of PBS (pH = 7.4), NADPH, probe substrates, and various concentrations of tested compounds. NADPH was added to initiate the reaction after a 5 min preincubation period at 37 °C in a thermos shaker. Of note, the volume of the final organic solvent in the incubation system should be below <1% (v/v) . All expmax and Km were calculated using GraphPad Prism v.8.0.2  via the Michaelis–Menten kinetic model. In addition, incubation times of 0–60 min were examined for mixed probe substrates. Various DLM protein concentrations (0.05–1 mg/mL) in the incubation mixture were carried out.The probe substrate concentrations were as follows: PH, BP, CLN, and CAN, 1–200 μM; TBD, 10–400 μM; DEX, 1–100 μM; and TS, 5–400 μM. The V2O = 80:20 (v/v). Finally, after filtering with a 0.22 μm membrane, an aliquot of 5 µL was injected into the UPLC-MS/MS for analysis.Then, 400 μL of cool ACN containing the 20 μL internal standard was added to terminate the reaction. Samples were vortexed for 2 min and centrifuged at 14,000 rpm for 10 min (4 °C). Next, the supernatant was steamed under nitrogen (40 °C) until dry. Then, it was dissolved with 200 µL of ACN: Hm in this study. Meanwhile, the Ki values were measured with various concentrations of probe substrates  and LKMS . Ki values of LKMS were determined if their IC50 values were lower than 100 μM [50 was calculated using the GraphPad Prism v.8.0.2 . Mode inhibition was examined based on a primary Lineweaver–Burk plot and a secondary plot.Inhibition assessment of CYP450 isoforms in DLM was performed with a fixed concentration of model probe substrates and a series of concentrations of LKMS ranging from 0 to 80 μM. The concentration of probe substrates was at a concentration of Kn 100 μM ,73. The 50 values were used to determine whether the inhibition of LKMS on CYP450 was time-dependent. The IC50 shift experiment was performed via the preincubation of LKMS in DLMs for 30 min at 37 °C with and without NADPH. The above mixture was then incubated for another 30 min in the presence of NADPH. The concentrations of LKMS were designated as 0.2, 2, 4, 6, 8, 10, 20, 40, and 80 μM, and the concentration of each probe substrate was based on each Km value. The concentrations of the probe substrates of CYP2A6, CYP2B6, and CYP2D6 were at single concentrations approximating their Km values [To characterize the reversible or irreversible mechanism of CYP450 inhibition via LKMS, the shifted ICm values .The effect of selective inhibitors on the rate of LKMS disappearance was investigated to identify the metabolizing enzymes of LKMS. The total volume of the incubation system was 200 μL, which contained the tested compound, inhibitors, PBS (pH = 7.4), LKMS, and NADPH. The study was performed via incubation with different inhibitors of CYP450 as follows: α-naphthoflavone , pilocarpine , Thio-TEPA , sulfaphenazole , quinidine , sodium diethyldithiocarbamate , and ketoconazole . The sample incubated without inhibitors was used as a negative control. The sample was incubated with dimethyl sulfoxide (DMSO) (25%) as a positive control in this study. Following this pilot, confirmatory experiments were conducted by incubating with DLM in the presence of specific CYP450 inhibitors.50 values and enzyme kinetic parameters were determined by plotting relative activities over the logarithm of the concentration of LKMS using GraphPad . The mode of the inhibitor was analyzed using a Lineweaver–Burk plot and a secondary plot for inhibition constant (Ki and αKi) values. All experimental data are shown as mean ± standard deviation (SD).The ICIn the current study, a UPLC-MS/MS method was established to simultaneously determine the metabolites of CYP450 probe substrates and to explore the effect of LKMS on the activities of dog CYP450 enzymes, both in vitro and in vivo. Importantly, the mechanisms of the inhibition of CYP450 caused by LKMS were investigated for the first time. Accordingly, our data suggest that LKMS can act as a mixed inhibitor, inhibiting CYP2A6, CYP2B6, and CYP2D6. Moreover, this inhibition via LKMS did not exhibit time-dependent behavior. All these results indicated the potential for DDIs between LKMS and drugs metabolized by CYP2A6, CYP2B6, or CYP2D6. However, further in vivo studies are needed to verify these potential effects.


BackgroundEarlier studies have shown that prevention of surgical site infection can achieve net cost savings when targeted to operating rooms with the most surgical site infections.MethodologyThis retrospective cohort study included all 231,057 anesthetics between May 2017 and June 2022 at a large teaching hospital. The anesthetics were administered in operating rooms, procedure rooms, radiology, and other sites. The 8,941 postoperative infections were identified from International Classification of Diseases diagnosis codes relevant to surgical site infections documented during all follow-up encounters over 90 days postoperatively. To quantify the inequality in the counts of infections among anesthetizing locations, the Gini index was used, with the Gini index being proportional to the sum of the absolute pairwise differences among anesthetizing locations in the counts of infections.ResultsThe Gini index for infections among the 112 anesthetizing locations at the hospital was 0.64 . The value of 0.64 is so large that, for comparison, it exceeds nearly all countries’ Gini index for income inequality. The 50% of locations with the fewest infections accounted for 5% of infections. The 10% of locations with the most infections accounted for 40% of infections and 15% of anesthetics. Among the 57 operating room locations, there was no association between counts of cases and infections (Spearman correlation coefficient r = 0.01). Among the non-operating room locations , there was a significant association (Spearman r = 0.79).ConclusionsTargeting specific anesthetizing locations is important for the multiple interventions to reduce surgical site infections that represent fixed costs irrespective of the number of patients . Staphylococcus aureus   review by the institutional review board because the activity is limited to analysis of deidentified medical record data.” The data used were limited to those collected as part of routine clinical practice.We studied all anesthetics administered by practitioners in the university’s department of anesthesia between May 2017 and June 2022. Nearly all cases (99.3%) were performed at one hospital campus comprising connected buildings with four surgical suites (adult inpatient (41.5%), adult outpatient (19.2%), pediatric (12.1%), and obstetrics (1.3%)), adult non-operating room anesthetizing locations such as gastroenterology (17.9%), and pediatric non-operating room locations such as magnetic resonance imaging (7.4%). The anesthesia department also provides care (0.7%) at a single off-site location for reproductive endocrinology cases . The start date of the dataset  was the first regular workday after the institution’s new pediatric hospital was fully open. The end date June 30, 2022) was chosen to allow a 90-day period to identify surgical site infections, matching the United States Centers for Medicare & Medicaid Services’ postoperative period for physician payment , changing door signage and locks [Targeting 40% of infections from just 10% of the anesthetizing locations has economic advantages for interventions that represent fixed costs by location  . The anend locks , selectind locks , or applnd locks ,17 for aThe finding of a lack of association between the counts of cases and surgical site infections among operating rooms reinforces earlier findings of the futility of cluster randomized trials for evaluating technologies installed in individual operating rooms ,37. TherS. aureus (or other pathogens) transmission and surgical site infections [Although Figure fections ,4-6. Casfections ,4-6. Daifections ,40. FiguObserved incidences of surgical site infectionsOur study was from one hospital in the United States. The overall incidence of surgical site infections was 4.7% among operating room cases, appropriately less than the 8.6%, 7.7%, 6.7%, and 6.7% incidences obtained in recent randomized trials ,41-43. TOther limitationsWhile our overall infection rate for all anesthetics was not inconsistent with the earlier studies, the lesser percentages could also reflect a limitation in that we used only ICD‑10‑CM diagnosis codes . IncorpoThroughout the paper, we referred to “surgical site infections.” However, a urinary catheter-associated infection represents surgical site infection after urological surgery. The same codes would identify urinary tract infections from repeated catheterizations in patients with catatonia receiving electroconvulsive therapy. While for surgical patients the use of ICD-10-CM diagnosis codes likely underestimates surgical site infections, among the patients who underwent anesthesia for minor therapeutic procedures, the incidences of infection attributable to the procedure may be overestimated. We doubt this would have any effect on our conclusions because the total counts of such infections are very small relative to surgery, gastroenterology, etc.The overall Gini index for surgical site infections among anesthetizing locations is large, exceeding the Gini index for income inequality among every country reporting to the Organisation for Economic Cooperation and Development. While the 50% of locations with the fewest surgical site infections accounted for 5% of infections, the 10% of locations with the most infections accounted for 40% of infections, considerably fewer than the 15% of anesthetics. These results are important because multiple interventions to reduce surgical site infections represent fixed costs . Organizations are encouraged to target anesthetizing locations (operating room and non-operating room sites) with the most surgical site infections per quarter. This strategy is entirely different from treating all patients, specialties, or rooms, as equivalent, and contrasts with targeting the few individual patients with the greatest incidences of infection.


Dynamic hip screws (DHS) and proximal femoral nail anti-rotation (PFNA) were recommended for basicervical femoral neck fracture (BFNF), however, with high rate of postoperative femoral neck shortening. The proximal femoral bionic nail (PFBN) was designed to decrease the postoperative complications associated with DHS and PFNA. The aim of this study is to compare the biomechanical characters of DHS, PFNA, and PFBN for fixation of BFNF.Using finite element analysis, we created a three-dimensional model of the BFNF for this investigation. The PFBN group, the PFNA group and the DHS + DS group were our three test groups. For each fracture group, the von Mises stress and displacements of the femur and internal fixation components were measured under 2100 N axial loads.The PFBN group demonstrated the lowest stress on the implants, significantly lower than the PFNA and DHS + DS groups. In terms of stress on the implants, the PFBN group exhibited the best performance, with the lowest stress concentration at 112.0 MPa, followed by the PFNA group at 124.8 MPa and the DHS + DS group at 149.8 MPa. The PFBA group demonstrated the smallest displacement at the fracture interface, measuring 0.21 mm, coupled with a fracture interface pressure of 17.41 MPa, signifying excellent stability.Compared with DHS and PFNA, PFBN has advantages in stress distribution and biological stability. We believe the concept of triangle fixation will be helpful to reduce femoral neck shortening associated with DHS and PFNA and thus improve the prognosis of BFNF. Basicervical femoral neck fracture (BFNF) is positioned between the femoral neck and the intertrochanteric region, constituting approximately 1.8% to 7.7% of all hip fractures . BFNF exDynamic hip screws (DHS), cannulated cancellous screws (CCS) and proximal femoral nail anti-rotation (PFNA) are commonly used devices in the treatment of BFNF . HoweverTo address these issues, we introduced the proximal femoral bionic nail (PFBN), which draws inspiration from the well-established Gamma nail and employs a cross-structured configuration of the fixating screw and supporting screw, mirroring the proximal femur's cantilever beam structure. In light of the above, the objective of this study was to conduct a comparative analysis of the biomechanical properties of the proximal femoral bionic nail (PFBN), the dynamic hip screw with de-rotation screw (DHS + DS), and the proximal femoral nail anti-rotation (PFNA) for the treatment of BFNF. We postulated that the PFBN would exhibit superior biomechanical properties.This study was reviewed and approved by the institutional review board, and the informed consent was obtained from the volunteer before the examination.A healthy 35-year-old man with a body weight of 75 kg was recruited as a volunteer participant. After excluding the deformity and abnormal condition of hip by X-ray examination, the left femur was scanned with the spiral computed tomography scanner . The scanning involved a slicing distance of 0.625 mm, and the raw data were stored as DICOM format. After that, the raw data were inputted into Mimics20.0 software  to establish the 3-dimension model and then the non-uniform rational basis spline (NURBS) was built by using the Geomagic Studio13.0 software . For accuracy, the authors employed manual segmentation to delineate the regions of cortical and cancellous bone within the CT images. The thickness of cortical bone varied across different regions due to anatomical differences. In our study, the cortical thickness ranged from 7.6 mm  to 1.3 mm . The Hypermesh 2014 software  was used to mesh the solid model of femur with C3D4 elements. The models of the DHS + DS, PFNA and PFBN were constructed in UG-NX 12.0  according to implants provided by the manufacturer . BFNF models were established and fixed with three devices by the UG-NX 12.0  was employed to apply axial pressure ranging from 0 to 600 N onto the surface of the femoral head at a rate of 5 N/s. Concurrently, the high-speed camera integrated within the GOM non-contact optical strain measurement system  captured the loading process at a frame rate of 7 frames/s. The resultant images were subsequently subjected to computer processing to derive displacement images and quantify displacement specific to the femur under an axial pressure of 600 N. Subsequent to data acquisition, the GOM Software 2021 was employed to select the appropriate starting point for calculations based on the collected images and to define the calculation area. Upon completion of the calculations, the displacement cloud diagram was automatically generated  could potentially reduce the likelihood of internal fixation failure, thereby contributing to the development of proximal femoral bionic nail (PFBN). The innovation of PFBN lies in its double triangle structure, composed of the supporting screw, fixating screw, and main nail. This design closely replicates the cantilever beam structure typically found in a normal proximal femur, resulting in a significant improvement in the postoperative stability following BFNF. The first component, known as the mixed triangle, is formed by the combination of the supporting screw, fixating screw, and the cancellous bone of the femoral head. This configuration significantly enhances the rotational stability of the hardware within three-dimensional space, ensuring a stable transfer of body-weight load to the junction of the supporting screw and fixating screw. The second component, referred to as the metal triangle, is constructed from the fixating screw, supporting screw, and main nail. The combined triangle and the main nail together create a stable cantilever beam structure that aligns with the anatomical structure and mechanical characteristics of the femoral neck. Moreover, the fixating screw is supported by both the main nail and the supporting screw, resulting in a double-pivot fixation. Consequently, this shortens the force arm, ultimately reducing stress concentration and enhancing fracture stability. Moreover, the tension stress of fixating screw can be significantly shared by the supporting screw due to horizontal placement. In our study, the PFBN group reduced stress on the implanted femur by 39.6% and 22.6% compared to the DHS and PFNA groups, respectively.As shown in displacement distribution, the fracture section stability and overall construct stability were higher in the PFBN model than that of DHS + DS and PFNA models, which meant that PFBN had good ability to resist compression and tension force. The peak stress of DHS + DS and PFNA was 1.3 and 1.1 times higher than that of PFBN. We believe the supporting screw plays an important role in reducing the stress concentration of fixation screw in PFBN, which could decrease the incidence of screw withdrawal, cut-out, and hip varus. In elderly patients with BFNF, who often have osteoporosis, PFBN could potentially offer improved stability and support for early postoperative rehabilitation exercises. However, it should be noted that our study did not specifically investigate the mechanical performance of PFBN in an osteoporotic model, and further research is needed to validate these assumptions.In addition, the peak stress of proximal femur in the PFBN model had the least value among all models, which demonstrated that PFBN had a decreased dependence on the integrity of femoral medial cortex. However, the peak stress and stress concentration of proximal femur in DHS + DS and PFNA models were located at the medial cortex of femur, which was different from that of PFBN. We consider that the results could be partially explained by the poor construct stability of the DHS + DS and PFNA. In a study on fracture morphology of BFNF patients, Collinge et al.  found 96To our knowledge, our study is the first study to test the mechanical properties of PFBN in BFNF. However, there are some limitations to this study. Firstly, despite superior biomechanical stability of PFBN, we did not verify whether the use of PFBN would result in better clinical outcomes. Further randomized comparative studies are needed to verify the clinical benefit. Additionally, it is important to consider that patients with osteoporosis may exhibit lower mechanical properties than healthy patients, potentially leading to higher displacements in such cases.In conclusion, we investigated the mechanical properties of PFBN, DHS and PFNA in the treatment of BFNF by using finite element analysis. Our study indicated that PFBN had better ability to resist shearing force and could improve the mechanical character compared with DHS and PFNA. Therefore, the use of PFBN should be considered in BFNF. Our findings provide a basis for further research and clinical utility of PFBN in BFNF patients.


Conclusions: Advanced age, dominant side, use of the cortical screw as the uppermost screw, and higher plate-screw density were related to proximal screw breakage. When the plate is removed after bony union or delayed union is shown in these situations, the possibility of proximal screw breakage should be kept in mind. Background: Locking a compression plate is a more favorable surgical technique than intramedullary nailing in the treatment of distal femur fractures. This study analyzed the risk factors of proximal screw breakage retrospectively, which was confirmed in the patients with plate removal after bony union. Methods: A total of 140 patients who were fixed by MIPO using ZPLP from 2009 to 2019 were identified. A total of 42 patients met the inclusion criteria and were included. The screw breakage group (12 patients) and the non-breakage group (30 patients) were compared. Results: Approximately 12 (28.6%) of 42 plate-removal patients showed proximal screw breakage. The breakage of proximal screws developed at the junction of the screw head and neck. The number of broken proximal screws averaged 1.4 (1~4). The breakage of the proximal screw even after the bony union is more frequent in older patients ( The incidence of femoral fractures varies in the literature and is reported to be approximately 3–6% ,3,4,5,6.® Periarticular Locking Plate (ZPLP®) for distal femoral fracture. Three experienced surgeons in two different university-affiliated hospitals performed these operations. This was a retrospective study based on medical documents and radiologic images. Between December 2009 and January 2021, 140 patients  aged 15 to 93 years underwent minimally invasive plate osteosynthesis (MIPO) using the ZimmerDistal femoral fractures with AO classification types IIIA, IIIB, and IIIC were included in the list. The exclusion criteria were patients with fixation failure and nonunion, patients fixed by dual plating, and those who did not undergo plate removal surgery.Of 140 patients, 98 were excluded from this study, and 42 met the inclusion criteria. Finally, 12 patients in whom proximal screw breakage was confirmed intraoperatively when the plate was removed were included in the screw breakage group, and 30 patients were included in the non-breakage group . The dem® Periarticular Locking Plate (ZPLP®) was inserted submuscularly and preliminarily fixed with temporary K-wires or drill bits before the insertion of real screws. Skeletal traction below the knee was applied until surgery for the prevention of muscle contracture and fracture site shortening. Patients were positioned supine on the radiolucent operating table under appropriate anesthesia. The lower leg was draped from the iliac crest to the foot for intraoperative assessment of the length, rotation, and angulation. The standard lateral parapatellar approach was used with the knee in 30-degree flexion supported by a rolled operation sheet. An incision was made over the lateral aspect of the distal femur, and the vastus lateralis muscle was retracted to expose the fracture site. With fluoroscopy, reduction of fracture was confirmed with coronal and sagittal views, and the ZimmerBefore definitive screw fixation of the plate, coronal alignment and sagittal alignment were checked again, and definite plate fixation with screws was performed. If the plate contour is not acceptable, which means the gap between the plate and bone is separated, a temporary cortical screw is used to reduce the gap between the plate and bone. The temporary cortical screw can remain or be removed. Rehabilitation started on the second postoperative day, changing from a long leg splint to a Velcro knee brace and continuous passive motion of the hip and knee joints. After discharge, patients were encouraged to perform straight leg-raising exercises. Non-weight bearing was recommended in patients with intraarticular fractures until callus bridging was visualized on plain radiographs; otherwise, tolerable weight bearing was taught. Coronal and sagittal plane angulations were assessed on anteroposterior and lateral full-length femurs, and knee x-ray films were captured immediately after surgery and at every outpatient follow-up visit. Generally, the patients were discharged from the hospital after 2 weeks of operation, which can be followed up every month until union is gained. Preoperative factors include age, gender, fracture classification, fracture configurations, femoral bowing, injury mechanism, time to injury, BMD, BMI, comorbidities, and ASA score. Fracture classification was classified by the AO classification, which defines 33-A as extraarticular, 33-B as partial articular, and 33-C as a complete articular fracture. Fracture configuration was classified into oblique, spiral, and transverse patterns. The ASA Physical Status Classification System was defined as ASA I as a normal healthy patient, ASA II as a patient with mild systemic disease, ASA III as a patient with severe systemic disease, and ASA IV as a patient with severe systemic disease that is a constant threat to life. Intraoperative factors include operation time, plate span width, screw density, screw fixation, or wiring of the fracture site. p < 0.05, and the statistical software used was SPSS 24.0 .Each group’s differences in mean values of continuous data were compared using the Student t-test, and the association of categorical data were examined using the Pearson chi-squared test. The significance level was set at There was a huge incidence of screw breakages. Approximately 12 (28.6%) of 42 plate-removal patients showed screw breakages. All screws were located proximal to fracture sites. The breakage of proximal screws developed at the junction of the screw head and neck. The number of broken proximal screws averaged 1.4 (1~4).An 83-year-old female patient showed multiple screw breakages at the junction of the screw head and neck after the removal of the plate . An 81-yRisk factors were analyzed, distinguishing between preoperative and postoperative factors.2) was 26.0, BMD (T-score) was −2.37, site (Rt:Lt) was 9 to 3, and the average ASA classification was 2.1. 7 patients had an underlying disease; 1 patient was diagnosed with obesity, and 1 patient was diagnosed with diabetes mellitus. In the non-screw-breakage group, the mean age was 55.5, the ratio of sex  was 10 to 20, BMI (kg/m2) was 24.3, BMD (T-score) was −1.87, site (Rt:Lt) was 11 to 19, and the average ASA classification was 1.9. 17 patients had an underlying disease; 2 patients were diagnosed with obesity, and 7 patients were diagnosed with diabetes mellitus  was 2 to 12, BMI , the plate span width was 3.53, the empty holes were 8.1, the wiring of patients was 4, the total number of filled screws was 11.3, the proximal was 4.25, the fracture site was 0.25, and the distal was 6.83. The plate screw density was a total of 0.53, proximal was 0.48, fracture site was 0.16, and distal was 0.96, and there were 6 fixation crossings over the fracture line. In the non-screw-breakage group, the mean operation time was 130 min, the length of the plate was 279 mm, 13.2 mm (hole), the plate span width was 4.93, the empty holes were 8.6, the wiring of patients was 5, the total number of filled screws was 10.7, the proximal was 3.96, the fracture site was 0.40, and the distal was 6.53. The plate screw density was a total of 0.47, proximal was 0.44, fracture site was 0.14, and distal was 0.91, and there were 10 fixation crossings over the fracture line . p = 0.023) and site of operation (p = 0.025) (Rt:Lt). Modifiable intraoperative surgical factors were plate screw density (p = 0.048) and screw configurations (p = 0.039). Non-modifiable preoperative risk factors were age  to lower area moment of inertia . This meImplant removal is not a routine procedure; when the surgeon considers the removal of the implant, screw breakage, and screw head stripping should be considered. These problems are so troublesome during the operation. If the surgeon prevents this problem, implant stiffness and material are also important. Moldevan et al. emphasized torch control during the insertion of screws, which are especially made of weak materials such as titanium alloy .Our study has limitations, such as a small number of cases and not being a comparative study with conventional plate fixation. Additionally, it is a retrospective study. Furthermore, only patients who achieved bone union were included, and cases of non-union or delayed union were excluded. Finally, the current study results showed that the plate length and number of screw holes did not affect the outcomes.The use of the MIPO technique with an LCP for the treatment of distal femoral fractures in the elderly has recently been reported to yield satisfactory results. The 28.6% incidence of screw breakage is a striking finding in this study.Even though LCP showed relatively good results, stress concentration on the screw and plate junction still occurred even after the bony union. Even though the exact risk factors were not figured out in this study due to the lack of cases, the authors suggest that the use of a locking screw at the proximal uppermost is recommended for the prevention of screw breakage after bony union. The stress on the locking screw head and neck junction is higher than that on cortical screws. If the whole screws were locking screws, this stress on the screw head and neck junction could be decreasing. Too high a density of screws also risks factors of screw breakage after gaining bony union. When such a surgical method is chosen, caution is required, as screw breakage occurs when the plate is removed after gaining bone union, despite the significant surgical benefits. Therefore, the surgeon should approach the treatment with caution, considering the possibility of breakage during the removal of the screw when using a cortical screw in elderly patients who underwent surgery on their dominant leg.


Although the positive association of partnership between DanceSport couples with competitive performance (CP) is documented, less is known about the mediating factors of this relationship. According to the related literature and self-determination theory (SDT), the present study finds and verifies that athlete engagement (AE) mediates the association between partnership and competitive performance.A total of 242 Chinese sports dancers were recruited using the purposive sampling method. The Partnership Scale-DanceSport Couples (PS-DSC), the Athlete Engagement Questionnaire (AEQ), and the Competitive Performance Questionnaire (CPQ) were adopted to collect data.The obligatory instrumental ties, expressive ties, and interpersonal perception scores are all positively correlated with both athlete engagement and competitive performance, and athlete engagement scores are positively correlated with competitive performance. Athlete engagement completely mediates the association between obligatory instrumental ties and competitive performance, and it partially mediates the association between expressive ties, interpersonal perception, and competitive performance, with the mediating effect accounting for 25.29 and 24.40% of the total effect, respectively.Athlete engagement mediates the association between DanceSport couples’ partnership and competitive performance. High levels of athlete engagement are needed to improve the chance of promoting obligatory instrumental ties, expressive ties, and interpersonal perception between DanceSport couples toward excellent competitive performance. Overall, the results represent an attempt to extend our understanding of the mechanisms by which the three partnership stereotype factors individually influence dancers’ cognitive and psychological states. Interpersonal relationship, in this context, is a very important environment for athletes to achieve excellent competitive results, which is supported by the literature on the coaches-athletes relationship  or mianzi (face).” It mixes instrumental and obligatory factors  refer to the reciprocal behavior tendency of elite dance couples based on the principle of obligation ruled by  factors , which i factors , p. 26.  factors , and par factors . Consequ factors , and the factors . Even wh factors . Therefo factors . These i“renqing” between partners, which is different from the contractual obligation emphasizing taking an interest. In Asian countries, such as China, the obligation between DanceSport couples is stressed , wrapping arms completely around a partner to ensure shoulder-to-knee contact, stroking a partner’s hair or face, dancing literally cheek to cheek, looking directly into one another’s eyes, and other idiosyncratic gestures” “He approaches her from behind until his chest touches her back, then thrusts his hands to her lower thighs and caresses her upwards. After grabbing her waist, he pushes her away and sharply pulls her back to him, provoking an impact of her back against his ribcage” “Shimmering in a beaded gold costume, Tanya alternately approached and fled from Edward, spiraling in toward him, hesitating, smiling, then spinning rapidly away. Hands caressed lightly, fleetingly, arms swirled in a serpentine embrace. Edward moved deliberately to showcase Tanya, their bodies forming luxurious and strangely balletic lines as she acquiesced to his touch. And all the while, their hips undulated in Latin motion, that sensuous pelvic movement that is the essence of the rumba/bolero. Desire begot desire, stirring reveries” “The judges watched as the dancers dipped low to the floor, the pelvis wed to the pelvis, man guiding woman into an “over sway.” The dancers moved cautiously, pulling themselves across the floor heel first. One couple had a decidedly Argentine look. Sleek in black, they revolved warily, crouched into the knees, Alicia exaggeratedly arched, Miguel proudly upright. They maintained this posture even as they punctuated their stalking with legs that flashed with lightning speed, hooking around hips and thrusting between thighs. Both executed the sharp libidinous jabs and pelvic climbs, which sometimes began or ended with the elegance of around de jambe. This eroticism vaguely recalled the knives carried by male dancers a century ago in Argentina as they challenged one another to combat Mack the Knife as a tango dancer. In Boston, the judges were not impressed” Second, long-term affection is a prerequisite for satisfactory performance. To be more specific, excellent competitive performance requires a prolonged period of systematic and professional practice . Like anWhile the positive effect of expressive ties between DanceSport couples on competitive performance has been recognized, no study has tested this idea with the widest possible range of investigations, which is the goal of our study.1.1.3.Interpersonal perception (IP) refers to the ability of elite dance couples to share and expose each other in the full process of taking competition as the goal, to sensitively perceive the psychological and behavioral tendencies of dance partners, including revealing their hearts, sharing, and understanding each other . InterpeIn addition, the DanceSport partnership is a special bond that mixes expressive ties and instrumental professional ties  and fall1.2.At present, few studies have explored the mediating variables between partnership and competitive performance, making it difficult to obtain reliable hypotheses from relevant studies on partnerships between DanceSport couples. Therefore, our study draws on the interdependence theory, which forms the basis of the coach-athlete relationship. We constructed this theory by conducting in-depth interviews with four couples. We also explored the pathway of influence that this theory suggests on competitive performance.p < 0.001) (Related studies and self-determination theory (SDT) support the hypothesis that athlete engagement mediates the association between partnership and competitive performance. To be more specific, < 0.001) .Based on this literature, it is believed that athlete engagement mediates the association between obligatory instrumental ties, expressive ties, and interpersonal perception, and competitive performance. To be more specific:Athlete engagement between obligatory instrumental ties and competitive performance. Sport dancers need to consciously observe the normative manners with their partners, including mutual respect, appreciation, and a sense of responsibility . According to Athlete engagement between expressive ties and competitive performance. A long-term relationship between partners triggers positive psychological feelings, such as recognition among both partners, thereby increasing their athlete engagement. More importantly, through the “mapping” function of mirror neurons in several areas of the human cerebral cortex, the inferior parietal lobule, the ventral premotor gyrus Broca’s area, and the posterior inferior frontal gyrus , the tigAthlete engagement between interpersonal perception and competitive performance.Relatedness is an innate and indispensable element for humans , 2004, a1.3.Analyzing DanceSport practices and related theories, we find that athlete engagement mediates the partnership between DanceSport couples  and competitive performance. However, of the studies we reviewed, none had tested the hypotheses with surveys. Hence, the present study aims to test the following hypotheses:H1: Athlete engagement partially mediates the association between obligatory instrumental ties and competitive performance.H2: Athlete engagement partially mediates the association between expressive ties and competitive performance.H3: Athlete engagement partially mediates the association between interpersonal perception and competitive performance.In addition, since athletic ability also plays a crucial role in competitive performance, it is used as a control variable in this study.2.2.1.Our sample consisted of 242 participants see  who had 2.2.2.2.1.We used the Partnership Scale-DanceSport Couples (PS-DSC) , which h2.2.2.We adopted the Athlete Engagement Questionnaire (AEQ) , which a2.2.3.Competitive performance includes the satisfaction degree of field performance and field performance; therefore, we used the Competitive Performance Questionnaire with four items . Further2.3.We used SPSS 22.0 to process and analyze the data. First, the Pearson correlation was used to examine the relationship between partnership, athlete engagement, and competitive performance. Second, all variables were standardized, and then Model 4 in PROCESS, developed by 2.4.Since the data used in this study was collected from self-report questionnaires, common method variance bias (CMVB), which affects the results and even draws wrong conclusions, was a potential concern. The possibility of CMVB is assessed when independent and dependent variables are measured under the same context and obtained from the same source. We adopted the harmony one-factor test to inspect whether there was an artificial covariation between the independent and dependent variables. The results showed that the variance of the first common factor explanation was 18.05%, which is lower than the 40% criterion proposed by 3.As shown in After controlling for gender, training time, partner time, and athletic ability, three regression models were established to analyze the influence of partnership quality on competitive performance through the moderating effect of athlete engagement. In the first model, obligatory instrumental ties were used as the independent variable. The model and regression coefficient are shown in β = 0.12, t = 2.01, p<0.05) when athlete engagement was added to the regression model. Obligatory instrumental ties by itself could not significantly influence competitive performance ; however, it could significantly influence athlete engagement  and athlete engagement could influence competitive performance . This demonstrated that athlete engagement completely mediated the effect of obligatory instrumental ties on competitive performance. Thus, H1 that athlete engagement partially mediates the association between obligatory instrumental ties and competitive performance is supported by this study.As seen in In the second model, expressive ties were used as the independent variable. The model and regression coefficient are shown in β = 0.35, t = 5.81, p<0.001) when athlete engagement was added to the regression model. Expressive ties could also independently significantly influence competitive performance  and athlete engagement , and athlete engagement could significantly influence competitive performance . The direct effect value of expressive ties affecting competitive performance was 0.26 . In addition, athlete engagement partially mediated the effect of expressive ties on competitive performance . The direct effect value and indirect value accounted for 74.71 and 25.29% of the total effect, respectively. Thus, H2 proposing that athlete engagement partially mediates the association between expressive ties and competitive performance is supported by this study.As seen in In the third model, interpersonal perception was used as the independent variable. The model and regression coefficient are shown in β = 0.34, t = 5.54, p < 0.001) when athlete engagement was added to the regression model. Interpersonal perception could also significantly influence competitive performance  and athlete engagement , and athlete engagement could significantly influence competitive performance . The direct effect value of interpersonal perception affecting competitive performance was 0.25 . In addition, athlete engagement partially mediated the effect of interpersonal perception on competitive performance . The direct effect value and indirect value accounted for 75.60 and 24.40% of the total effect, respectively. Thus, H3 on athlete engagement partially mediating the association between interpersonal perception and competitive performance is supported by this study.As seen in 4.Our results indicate that athlete engagement completely mediates the association between obligatory instrumental ties and competitive performance (H1), partially mediates the association between expressive ties and competitive performance (H2), and partially mediates the association between interpersonal perception and competitive performance (H3). These findings demonstrate that obligatory instrumental ties, expressive ties, and interpersonal perception between DanceSport couples and athlete engagement are critical factors influencing individuals’ competitive performance. The findings are a result of the self-determination theory (SDT) and research mentioned in the current study’s introduction and other theories.4.1.In our study, athlete engagement completely mediates the association between obligatory instrumental ties and competitive performance. It suggests that athlete engagement influences the relationship between obligatory instrumental ties and competitive performance. On its own, obligatory instrumental ties are unable to significantly influence competitive performance, contradicting the hypothesis of economic man. Moreover, it also contradicts the theory of group dynamics, which holds that a harmonious interpersonal atmosphere within a group can stimulate the creation of excellent competitive performance in a sports team. For dance dyads, their partnership is premised on meeting specific needs and achieving competitive goals. The reason may lie in special norms inherent in Chinese culture relating to instrumental relationships, which weaken the utilitarian purpose and pay more attention to “renqing” and “mianzi” . Establi4.2.Our results indicate that athlete engagement partially mediates the association between expressive ties and competitive performance (H2). This finding demonstrates that expressive ties and athlete engagement are critical factors influencing individuals’ competitive performance, which also reaffirms findings under relevant literature . On the On the other hand, expressive ties, including long-term affection, which requires the dancers to appreciate, care for, and be harmonious with their partners, refers to an emotional tie generated in long-time interactions in life and professional contexts between dance partners. According to 4.3.Our results indicate that athlete engagement partially mediates the association between interpersonal perception and competitive performance (H3). This finding demonstrates that interpersonal perception between DanceSport couples and athlete engagement is a critical factor that influences individuals’ competitive performance. This finding is not only proven under SDT and its applied research but is also supported by many psychological theories. According to Social exchange theory and Pavlov’s dynamic stereotype theory also support our results. To be more specific, according to social exchange theory, when dancers perceive that their sense of unfamiliarity with their partners has diminished and instead perceive sincere and expressive ties between them, they tend to communicate in a more friendly manner, often displaying positive emotional tendencies. This can lead to behaviors that are beneficial for achieving their desired goals. On the contrary, the performance (such as persistence and success) of athletes can be affected if the partnership is belittled or ignored  . Therefo5.This study found that based on relationship-related theories, such as SDT and Pavlov’s dynamic stereotype theory, athlete engagement mediates the association between obligatory instrumental ties, expressive ties, interpersonal perception, and competitive performance. Among them, the intermediary effect of athlete engagement explains 100% of the variation of obligatory instrumental ties. It partially mediates between expressive ties, interpersonal perception, and competitive performance, respectively, with the upper and lower limits of the 95% confidence interval of the mediating effect being  and . The effect values of 0.088 and 0.082 accounted for 25.29 and 24.40% of the total effect. Overall, the results represent an attempt to extend our understanding of the mechanisms by which partnerships influence dancers’ cognitive and psychological states.In addition, the results apply to countries influenced by Confucian culture, such as South Korea and Japan, and apply to professional athletes rather than amateur athletes.6.The findings of this study should be considered in light of two strengths and two limitations. The two strengths include: 1) offering a path for transforming DanceSport partnerships into competitive performances and providing dancers with high-quality ideas for strengthening partnerships; 2) Further strengthening the scientific nature of the self-determination theory and providing evidence to enrich and improve the theory of self-determination to a certain extent. Nonetheless, due to the preliminary nature of our study, two limitations should also be noted. First, the sample comprised dance couples only from China. This has implications for the international generalizability of the study findings. Future research with diverse samples from other countries should be considered. Second, the sample size needs to be expanded further. Because of the need to control as much as possible the influence of referees, lighting, venues, and other factors on the results of the study, we obtained data from a single match. However, it is difficult to increase the sample size beyond 242 people in a single match. In the future, other methods need to be explored to compensate for the difficulty of expanding the sample size so as to avoid statistical bias in the study.7.DanceSport couples are cognitively, emotionally, and behaviorally interdependent. However, the two have gender and individual differences, and how their psychology and behavior affect each other needs to be further studied. Our study suggests that, in the future, the actor-partner interdependence mediation model  can be used to further explore the relationship between partnerships, athlete engagement, and competitive performance. Thus, opinions can be provided to male and female dancers, respectively, to ensure excellent competitive performance.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving humans were approved by the Ethics Committee of the Wuhan Sport University. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.XL: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing. BW: Conceptualization, Funding acquisition, Writing – original draft. XW: Funding acquisition, Methodology, Writing – review & editing. QS: Writing – review & editing.


This study aimed to investigate the techniques and indications of upper sacroiliac screw fixation for the dysmorphic sacrum.The dysmorphic sacra were selected from 267 three-dimensional pelvic models. The dysmorphic sacra which couldn’t accommodate a 7.3 mm upper trans ilio-sacroiliac screw were classified as the main dysmorphic sacra. Then, the size of the bone corridor, the length of the screw in the corridor, and the orientation of the screw were measured. The insertion point on the sacrum was identified by two bone landmarks.totally, 30.3% of sacra were identified as the main dysmorphic sacra. The inclinations of the screw oriented from posterior to anterior were (21.80 ± 3.56)° for males and (19.97 ± 3.02)° for females (p < 0.001), and from caudal to cranial were (29.97 ± 5.38)° for males and (28.15 ± 6.21)° for females (p = 0.047). The min diameters of the corridor were (16.31 ± 2.40) mm for males and (15.07 ± 1.58) mm for females (p < 0.001). The lengths of the screw in the Denis III zone were (14.41 ± 4.40) mm for males and (14.09 ± 5.04) mm for females (p = 0.665), and in the Denis II+III zones were (36.25 ± 3.40) mm for males and (38.04 ± 4.60) mm for females (p = 0.005). The rates of LP-PSIS/LAIIS-PSIS were (0.36 ± 0.04) for males and (0.32 ± 0.03) for females . The lengths of LPM were (8.81 ± 5.88) for males and (-4.13 ± 6.33) for females .When the sacrum has the features of “sacrum not recessed” and/or “acute alar slope”, the conventional trans ilio-sacroiliac screw couldn’t be placed safely. The inclination oriented from posterior to anterior and from caudal to cranial are approximately 20° and 30°, respectively. The bone insertion point locates in the rear third of the anterior inferior iliac spine to the posterior superior iliac spine. The sacroiliac screw is not recommended to fix the fractures in Denis III zone. The posterior pelvic ring is the main structure of weight-bearing, therefore, anatomical reduction and rigid fixation of the posterior ring are the main purposes of the surgical management for unstable pelvic ring traumatic injures. Percutaneous sacroiliac (SI) screw fixation has been a safe and reproducible method for sacroiliac dislocation and sacral fracture , 2, howeAll experimental protocols were approved by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University. 267 healthy adult pelvises of 64-slice spiral CT scans data were collected from January 2018 to January 2020 in the Medical Imaging Department. The pelvic 3D projects were reconstructed by the Materialize’s interactive medical image control system (Mimics) 16.0 software based on CT data. These dysmorphic sacra were identified according to the six qualitative characteristics  as folloFour screws were placed in the upper sacral pedicle and were obliqued to its axis. The four screws were tangent with the anterior-superior, anterior-inferior, posterior-superior and posterior-inferior cortex of the upper sacral pedicle, respectively, and were intersected at points M1, M2, M3 and M4 on the lateral cortex of ilium  and posterior superior iliac spine (PSIS), were assisted to locate the insertion point on the ilium surface. As Fig. To find out the best inclination angles, the tail of the screw was fixed at P. On the coronal scan, the tip of the screw was rotated around the insertion point until it was tangent with the nearest superior or inferior cortical bone of the upper sacral pedicle Fig. a. Thus, As reported, in the upper sacral pedicle, the superior-inferior diameter was smaller than the anterior-posterior diameter , 19. TheSPSS 19.0 software was chosen for the analysis. The difference between rates was tested by chi-square test. Measurement data were expressed in mean differences ± standard deviation and analyzed by the independent sample t-test. p < 0.05 was required for a statistical significance.x2 = 0.005, p = 0.943) on CT scan. Therefore, in the following paper, “residual disc” was not regarded as a dysmorphic characteristic anymore. Except for the “residual disc”, 39.3% of the dysmorphic sacra  were selected from all subjects. The “acute alar slop” was the most frequent detected sign, followed by “dysmorphic upper sacral foramen”, “mammillary processed”, “sacrum not recessed” and “tongue-in-grove” . The “residual disc” was identified in 98.1% of all samples . The cranial inclination angle were (29.97 ± 5.38) °for males and (28.15 ± 6.21)°for females .The anteversion inclination angles of the screw were (21.80 ± 3.56)° for males and (19.97 ± 3.31)°for females . The lengths of the screw in different Denis zones were shown in Table The min diameter of the corridor were 16.31 ± 2.40) mm for males and (15.07 ± 1.58) mm for females (.40 mm foP-PSIS/LAIIS-PSIS as well as LPM. The rates of LP-PSIS/LAIIS-PSIS were (0.36 ± 0.04) for males and (0.32 ± 0.03) for females .The distance from P and AIIS to PSIS as well as the distance from P to line AIIS-PSIS were shown in Table 3. The location of the insertion point was estimated by the two bone landmarks and was described by the ratio of LIn the early 1990s, the percutaneous fixation via SI screws began to be used to stabilize posterior pelvic ring, sacral fractures and sacroiliac joint injuries. Compared with the classical method, this new method decreases operating time, soft tissue injury, blood loss, and infection risk . HoweverIn our study, the “residual disc” could be seen on CT scans for almost samples (98.1%). Weigelt found that the “residual disc” was the most frequent detected sign which present in 70% of all patients . Miller Although, in the classification of Routt, there are six dysmorphic characteristics, only “sacrum not recessed” and “acute alar slope” complicate the safe placement of SI screws much. The alar slope is more acute in these patients, and it is associated with a notable inferior-lateral-posterior to superior-middle-anterior orientation. This oblique dysmorphic alar osteology makes TISI screw fixation impossible. Both the two characteristics often show on one sacrum. This phenomenon may be conducted by: in the growth and development of our body, the middle part of the sacral ala develops with the rising sacral body, however the lateral part is still connected with the inferior sacroiliac joint. As the rising of the upper sacral body, the round foramen may be stretched non-circular. The mammillary processes are deformed or under developed residual transverse processes from the sacralized L5 vertebral body. Above all, the appearance of the main dysmorphism often combines with minor dysmorphism.Since the lumbosacral junction is one of the most variable regions of the spinal column , Miller For non-dysmorphic sacrum, indications for upper SI screw fixation include complete sacral fractures, sacroiliac joint disruptions, and combinations of these posterior pelvic injuries followed reduction. Incomplete sacral fractures and sacroiliac joint disruptions that contribute to pelvic ring instability may be addressed with SI screw fixation .In 1988, Denis  classifiP-PSIS/LAIIS-PSIS were 0.36 for males and 0.32 for females (Table PM were 8.81 mm for males and − 4.13 mm for females (Table Although the SI screw malposition rate is the lowest in the computer-assisted navigation techniques, conventional fluoroscopy is easier to get in most hospitals , 7–9. BeNon- and dysmorphic sacrum have distinct anatomic differences that must be noted prior to surgical intervention, especially the characteristics of “sacrum not recessed” and “acute alar slope”. For these patients, the skin insertion point which was more posterior and inferior than non-dysmorphic sacrum and the bone insertion point was located nearly the rear third of line AIIS to PSIS. The inclination oriented from posterior to anterior was about 20°, and that from caudal to cranial was about 30°. What needs specially attention was that the upper SI screw was not recommended to fix the fractures in Denis III zones. The correct insertion point and orientation could help to reduce the rate of malposition, reduce the radiation exposure time and improve the clinical results of patients.