The systems containing SPAH, in the absence of XG, showed shear-thinning flow behavior, which was changed to thixotropic with the addition of XG. Viscoelastic properties of emulsions containing over 0.2% of XG were confirmed by oscillatory rheological tests, demonstrating the dominance of elastic (G’) over viscous (G”) modulus.There is a growing need for natural ingredients that could be utilized for the production of food, pharmaceutical, and cosmetic emulsions. Soy protein acid hydrolysate (SPAH) is a plant-based additive used in the food industry mainly as a flavor enhancer. For the purpose of this work, however, it was mixed with a well-known natural polysaccharide, xanthan gum (XG), to produce stable 30% (w/w) sunflower oil-in-water emulsions using a rotor-stator homogenizer. In order to assess the emulsifying properties of the SPAH and its mixtures with XG, the surface tension properties of their water solutions, particle size, creaming stability, and rheological properties of the emulsions were investigated. Since the emulsions prepared using only SPAH, in various concentrations, were not stable, systems containing 5% of SPAH and 0.1, 0.2, 0.3, 0.4, or 0.5% of XG were then studied. The increase in concentration of the macromolecule led to an increase in creaming stability. The emulsions with 5% SPAH and 0.5% XG were stable for at least 14 days. The increase in XG concentration led to a decrease in d Demand for natural ingredients in the food, pharmaceutical, and cosmetics industries is increasing due to consumer preferences and the move towards sustainable raw materials ,2. The sSoy protein hydrolysate (SPH) is a mixture composed mainly of amino acids, peptides, and proteins ,11. SmalXG is a well-known natural polysaccharide, approved by the United States Food Administration as a safe food additive without quantity limitations . It is uKeeping in mind the beneficial aspects of SPH and XG for the food, pharmaceutical, and cosmetic industries, SPAH and XG were mixed together in this study as an emulsifier and a stabilizer, respectively, in order to obtain oil-in-water emulsions with desirable stability and rheological properties. For this purpose, the surface tension properties of SPAH-XG mixtures in water solutions, creaming stability, dispersion, and rheological properties of the emulsions were investigated. According to the available literature, emulsions stabilized using SPAH together with XG have not been studied yet.Therefore, the aim of this study was to investigate the emulsifying ability of SPAH in the absence and presence of XG as well as the influence of the concentration of the polysaccharide on particle size, creaming stability, and rheological properties of the emulsions in which SPAH was used as an emulsifier. It is envisioned that the results of this study will be useful for the development of novel food, pharmaceutical, and cosmetic products, especially emulsions, with natural and sustainable raw materials.Soy protein acid hydrolysate was purchased from Sigma-Aldrich, Saint Louis, MO, USA (product number: S1674). Xanthan gum, Xanthural 180 CP, food grade, having a viscosity of 1561 mPa·s for a 1% solution in 1% KCl solution, according to the certificate of analysis supplied by the producer, was donated by CP Kelco, Atlanta, GA, USA. Sodium azide was obtained from Sigma-Aldrich, Taufkirchen, Germany (product number: 71290). Sunflower oil, produced by Dijamant, Zrenjanin, Serbia, was purchased in the local market. Distilled water was used for the preparation of all solutions and dispersed systems in the study. All reagents were used without further purification.Surface tension measurements were carried out on three sets of water solutions containing SPAH in various concentrations using the du Noüy ring method on a Krüss K20 Easy Dyne tensiometer  at 25 ± 0.1 °C. In the first set, aqueous solutions contained SPAH in the following concentrations: 0.1, 0.2, 0.3, 0.5, 0.7, 1.0, 2.0, 3.0, 4.0, or 5.0% (w/w). The second and third sets of water solutions contained the same SPAH concentrations alongside XG at constant concentrations of 0.02 and 0.05% (w/w), respectively. The surface tension of the distilled water and the aqueous solutions of XG with 0.02 or 0.05% (w/w) was also determined. The concentration of the preservative, sodium azide, was set to 0.01% (w/w) in all investigated solutions. The surface tension measurements were performed five times for each aqueous solution. The average surface tension values were determined along with the standard deviation. In this way, three sets of data were obtained.®-Werke GmbH & Co., Staufen, Germany) was used for the preparation of all investigated emulsions. In order to prepare the disperse systems, the homogenizer operated at 15,000 rpm for 20 min in a water bath with a constant temperature of 25 °C.All emulsions prepared in this study contained 30% of oil phase (w/w) and various concentrations of SPAH and XG. Firstly, emulsions containing only SPAH, i.e., emulsions without XG, were prepared. These emulsions had the following concentrations of SPAH: 3, 5, or 7% (w/w) with respect to the total mass of the emulsion. Secondly, emulsions containing both SPAH and XG were prepared. The obtained emulsions had 3 or 5% of SPAH (w/w) with respect to the total mass of the emulsion and the following concentrations of XG in the continuous phase: 0.1, 0.2, 0.3, 0.4, or 0.5% (w/w). Sodium azide was used as a preservative in all emulsions. The concentration of salt in the aqueous phase of all emulsions was set to 0.01%. A rotor-stator homogenizer , d (0.1), and d (0.9), which represent diameters at 10%, 50%, and 90% cumulative volume, respectively,Span—the width of a droplet size distribution, calculated using the equation:The particle size distribution in emulsions was determined by the laser light scattering method using Mastersizer 2000 . All emulsions were left for 24 h after preparation to avoid air bubbles incorporating into the emulsion. Each measurement was carried out in triplicate, and the average value ± standard deviation was taken as a result. Results were analyzed using Malvern software, and particle size distributions were reported using several parameters:H (%), which is used to express creaming stability, was calculated as a ratio of the height of a serum layer at the bottom (SH) to the total height of an emulsion sample (TH) in the graduated cylinders. The following formula was applied to determine the creaming index values:SH represents the heigh of a serum layer and TH is the total height of an emulsion sample.Creaming stability was investigated for the oil-in-water emulsions with 3 or 5% of SPAH (w/w). Moreover, the creaming stability was examined for the systems having 3 or 5% of SPAH (w/w) and the following concentrations of XG: 0.1, 0.2, 0.3, 0.4, or 0.5% (w/w). Once prepared, the oil-in-water emulsions were transferred to graduated cylinders and monitored visually every day during the 14-day (336 h) period. The value of the creaming index H (%) was determined for each emulsion, every day, during the 14-day period.The value of the creaming index −1 for 120 s. Then, the shear rate was maintained at 150 s−1 for 60 s, and finally, it was decreased to 0 s−1 for 120 s. A power law model (Equation (3)) was used to analyze the flow curves:τ (Pa) is shear stress, −1) is shear rate, n  is flow behavior index, and K (Pa sn) is consistency index.The rheological properties of emulsions were determined by a controlled-stress HAAKE MARS rheometer . The measurements were conducted at a constant temperature of 25 ± 0.1 °C using cylinder DG41 Ti, 24 h after emulsion preparation. The rheological method included hysteresis loop tests. Firstly, the samples were exposed to an increasing shear rate from 0.001 to 150 sOscillatory experiments were performed through amplitude and frequency sweep tests. Amplitude sweep tests were conducted in order to determine the linear viscoelastic region (LVR) by recording the storage (G’) and loss (G”) moduli versus shear stress (0.01–50 Pa) at a constant frequency (1 Hz). From LVR, appropriate shear stress was detected in the middle of LVR. In frequency sweep tests, the G’ and G” moduli were recorded versus frequency (0.1–10 Hz) at constant shear stress (determined from amplitude sweep tests).t-test was carried out at the significance level of 0.05, using the one-way ANOVA procedure and Tukey’s multiple comparisons tests with OriginPro 2022 software (v. 9.9.0.225).To determine if there was a statistically significant difference between the obtained data, the In order to investigate the existence of interactions between a surfactant and a macromolecule, i.e., a stabilizer, usually surface tension measurements are employed . TherebyBased on the results presented in Droplet size and size distribution determine many emulsion properties, such as appearance, texture, rheology, and stability. These parameters are the main indicators of the homogenization process since emulsification includes two processes: (1) droplet disruption that increases the specific surface area and (2) stabilization of the newly formed interface by the emulsifier through the prevention of droplet coalescence. Emulsion droplet size is thus the consequence of equilibrium between droplet break-up and re-coalescence ,23.4,3, was used as the mean diameter based on the volume frequency. This volume-weighted mean diameter is sensitive to the presence of large particles within a polydisperse system and is thus useful for detecting flocculation or coalescence occurring at low extents in emulsion systems [The droplet size and size distribution parameters of the emulsions prepared and stabilized with SPAH and XG are presented in  systems .Droplet size measurements of emulsions demonstrated that the increase in SPAH concentration from 3 to 7% led to the formation of smaller droplets during homogenization. The addition of XG to the emulsions containing 5% of SPAH resulted in the formation of significantly smaller droplets in comparison to the corresponding emulsion without XG. Moreover, the tendency to reduce the droplet sizes with the increase in the XG concentration from 0.1 to 0.5% was demonstrated as well, but without statistical significance. Besides, the emulsions stabilized with XG showed a narrower droplet size distribution (span) in comparison to the emulsions without XG.The particle size distribution of the emulsions containing 5% SPAH and increasing XG concentrations is shown in In this study, the pattern of droplet size distribution did not significantly change after a 7-day storage period. While the droplet size significantly increased in the emulsions stabilized with SPAH at concentrations of 3% and 5%, this was not the case in any of the XG-containing SPAH-stabilized emulsions . These rConsidering the surface tension measurement results of this study, which indicate attractive interactions between SPAH and XG, the stability of the prepared emulsions may be explained accordingly. The occurrence of attractive electrostatic interactions, along with other intermolecular interactions such as hydrogen bonds, has been previously determined between XG and amaranth and bean protein isolates . BesidesOn the contrary, in the study of Ye et al. 2004), the addition of XG to the emulsions formed with 4% of extensively hydrolyzed whey proteins led not only to droplet flocculation through a depletion mechanism and an enhanced creaming rate but also to the coalescence of the droplets within the flocculated emulsions. Given that the emulsion-forming properties were not affected by the increase in concentrations of XG, the authors concluded that re-coalescence during emulsification and coalescence during storage of emulsions occur via different mechanisms . The res, the addIt is well known that emulsions are thermodynamically unstable systems susceptible to gravity-induced separations, i.e., creaming and sedimentation, flocculation, coalescence, Ostwald ripening, as well as phase separation . CreaminThe results of the creaming stability investigations, in this study, are shown in The dependence of the creaming index values after 14 days of storage on XG concentration for the emulsions having 3 or 5% of SPAH is shown in Two different rheological measurements of emulsions were performed in this study: continuous rotational tests to obtain the flow curves and an oscillatory stress sweep to determine the linear viscoelastic region (LVR), where SPAH and XG concentrations were varied in order to determine their impact on the system’s rheology.K), as an indicator of the viscous nature of a system, and the flow behavior index (n), which demonstrates the extent of non-Newtonian behavior, were calculated. The fitting results of consistency index K and flow behavior index n for all investigated emulsions are presented in Flow curves acquired from continuous rotational tests were fitted by the power law equation, and the consistency index  flow behavior, which is manifested by an apparent viscosity decrease with the increase in shear rate. Neither the K and n indexes were significantly impacted by the XG concentration. The rise in XG concentrations significantly increased the consistency index, which is in correlation with the apparent viscosity of the system. This result was expected considering the excellent thickening properties of XG and its impact on continuous phase viscosity in emulsions [n indexes of prepared emulsions indicates more pronounced non-Newtonian, pseudoplastic flow behavior of SPAH-stabilized emulsions containing higher concentrations of XG. Similar results were obtained in the study of Chen et al. (2016), where both consistency and flow behavior indexes were significantly affected by the XG concentration in oil-in-water emulsions formed with rice dreg protein hydrolysate and stabilized with XG [The rheograms of shear stress versus shear rate (flow curves) for 5% SPAH emulsions with increasing concentrations of XG are shown in mulsions . On the  with XG .The impact of XG on the occurrence of time-dependent, i.e., thixotropic flow, behavior of SPAH-stabilized emulsions is indicated by the hysteresis area values . The hysShear-thinning flow is the most common type of non-ideal behavior exhibited by food emulsions, and it may occur due to various reasons, such as alteration of the spatial distribution of the particles induced by the shear field or deformation and disruption of flocculated particles in the emulsions . PseudopPrevious studies have demonstrated that XG is responsible for the shear-thinning flow character of the emulsion systems since it is a high molecular weight, non-adsorbing hydrocolloid, which may induce the flocculation of oil droplets even at low concentrations in oil-in-water emulsions and the formation of a three-dimensional network . These eThe viscoelastic properties of emulsions were analyzed by oscillatory rheological tests. First, an amplitude sweep was performed, and the storage G’ and loss G” moduli were plotted against shear stress τ in order to detect the linear viscoelastic region (LVR). Emulsions that contained only SPAH , as well as the emulsions containing 5% SPAH with 0.1% and 0.2% XG, did not show LVR. For the emulsions containing 5% SPAH and XG in concentrations of 0.3%, 0.4%, and 0.5%, the frequency sweep tests were conducted at the mean shear stress values within the LVR in order to avoid damage to the internal structure of the system by the strain imposed during the measurements. The results of frequency sweep tests for the emulsions that exhibited LVR are presented in The frequency sweep showed that the increase in XG concentration led to an increase in the G’ and G” values of emulsions. The emulsions were characterized by dominating elastic behavior (G’) over viscous behavior (G”) within the entire range of frequencies (0.1–10 Hz), suggesting a gel-like network structure with mainly elastic behavior, as noticed in previous articles ,47. OnlyThe results of frequency sweep tests are in accordance with the creaming stability of the prepared emulsions , consideThe surface tension measurements indicated a minor influence of XG on the surface activity of SPAH. The increase in XG concentration in the emulsions led to a decrease in droplet size, which remained unchanged during the storage period of 7 days. The addition of XG prevented coalescence and improved creaming stability. The emulsions with 3 or 5% of SPAH and 0.5% of XG were stable for at least 14 days. A sharp increase in the creaming stability was noticed when XG was used at concentrations higher than 0.2%, as a result of the rapid increase in viscosity of the continuous phase and gel-like network structure formation. A shear-thinning (pseudoplastic) flow behavior of emulsions prepared with SPAH, in the absence of XG, was also observed. The addition of XG led to the occurrence of thixotropy. Only the emulsions containing XG at concentrations higher than 0.2% (w/w) were characterized by dominating elastic behavior (G’) over viscous behavior (G”), as a result of the gel-like network structure formation, indicating that the rheology measurements can be used to predict creaming stability. Generally, the presence of XG in the emulsions stabilized with SPAH positively affects the stability of the systems.


The malleable penile implant is often considered an inferior device to the three-piece inflatable penile prosthesis implant. Nonetheless, the malleable prosthesis has its unique advantages such as lower cost, easier to perform and fewer mechanical complications than inflatable prostheses. Furthermore, its role can be extended to patients with issues relating to poor manual hand dexterity, those undergoing a salvage for infection prosthesis and as an emergency surgical measure in patients presenting with acute ischaemic priapism. Over the past few decades, there have been numerous design and technological advancements to improve overall clinical efficacy, mechanical durability, axial rigidity and device concealability of malleable penile prostheses. The following article provides a narrative review of the six major contemporary malleable penile prosthesis devices in the commercial market, namely, the Coloplast Genesis prosthesis, the Boston Scientific Tactra prosthesis, the Zephyr ZSI 100 and 100  FTM devices, the Rigi10 prosthesis, the TUBE malleable prosthesis and the Shah prosthesis and evaluates the published outcomes. Appropriate patient selection and strict counselling regarding what to expect with malleable prostheses coupled with adherence to safe surgical principles are paramount to ensure excellent clinical success and patient satisfaction rates. Malleable  prostheses are often less costly, easier to perform and have fewer mechanical complications than inflatable prostheses. It is known that key factors such as device cost, hand dexterity, state of the penile tissue and patient’s medical comorbidities will play a role in the decision-making on the type of penile prosthesis surgery.3While the introduction of the modern inflatable penile prosthesis (IPP) implant has revolutionized the treatment for erectile dysfunction (ED), the malleable penile implant was the first mainstream penile implant of the modern era since the late 1960s following the creation of a silicone prosthesis. Over the next two decades, many malleable prostheses were produced and marketed and some even reach commercial success with high patient satisfaction rates such as the Jonas malleable penile prosthesis and the AMS (now owned by Boston Scientific) malleable 600 model series, Duraphase-II and Spectra malleable penile prosthesis.For malleable implant recipients, the penis remains in a semirigid state permanently, and the patient can bend the prosthesis upwards to engage in sexual intimacy. Drs Small and Carrion were largely credited for introducing modern and successful Small-Carrion malleable penile prosthetic implantation in patients.® prosthesis , the TUBE malleable prosthesis  and the Shah prosthesis . These malleable prostheses have undergone stringent internal clinical testing and external review from relevant national regulatory bodies to ensure these devices are safe and mechanically reliable. The following article provides an overview of each of these malleable prostheses in terms of device specifications and evaluates the current evidence on their clinical outcomes.At present, there are six major malleable penile prosthesis devices available in the commercial market : the ColThis narrative review evaluates commercially available malleable penile prostheses currently available in the market and involves a review of the literature published on MEDLINE and EMBASE databases from June 1990 to June 2022. The following key terms, namely, ‘malleable penile prosthesis’ and ‘noninflatable implant’ were utilized. Relevant published guidelines on penile prosthesis implantation were reviewed and synthesized into this review. This narrative review summarizes relevant features unique to the design and technology for each malleable prosthesis  and publ It consists of a flexible silicone elastomer device with design specifications including a hydrophilic polyvinylpyrrolidone coating that enables a surgeon to select and customize the choice of antibiotic(s) preparation and elution. The device has a silver core but no internal springs, cables or moving components to ensure mechanical reliability and prevents the device from auto spring-back. Its distal shaft column has sufficient rigidity to prevent device buckling during sexual activity.The Coloplast Genesis was introduced in 2004.The Genesis prosthesis rod can be trimmed to the appropriate length and available cylinder lengths were 14–23 cm, 16–25 cm and 18–27 cm while the cylinder diameter comes in sizes 9.5, 11 and 13 mm. No special tools are required, and three different sizes of tail caps  are available for adjusting the prosthesis length. The bend flexibility for the Genesis rod is around 90 degrees. In a comparative study between the Coloplast Genesis model and the older AMS Spectra device, there was no significant difference detected between the devices  to indicate a difference in device superiority. Another recent publication highlighted that a larger diameter Genesis device was associated with higher complication rates without higher patient satisfaction rates.Earlier publication on Genesis prostheses reported excellent clinical outcomes in patients with combined ED and Peyronie’s disease.The Tactra™ malleable penile prosthesis was introduced in 2019 and in comparison with the original Spectra device, this next-generation malleable prosthesis from Boston Scientific company has a dynamic Nitinol  core encased by a proprietary dual-layer silicone exterior to provide device rigidity and durability.Similar to the Genesis device, the Tactra implant has trimmable exterior etchings for corporal size optimization and is available in three different cylinder lengths of 14–23 cm, 16–25 cm and 18–27 cm with corresponding cylinder diameters 9.5, 11 and 13 mm. An insertion-fit rear-tip extender is available in 0, 0.5 and 1 cm to adjust the final cylinder length. The bend flexibility for the Tactra device is 120 degrees.To date, there is no published study on the Tactra device. It has a propriety HydroShield coating that is hydrophilic in nature to allow for easier device implantation and choice of antibiotic elution. Like the Coloplast Genesis device, it is made of flexible silicone elastomer and has a good shape memory that minimizes spring backs. The Rigi10™ prosthesis is available in six different diameters  and two lengths of 23 cm (for 9- and 10-mm diameters) and 25 cm . Secure-Fit Extenders come in 0.5 and 1.0 cm sizes to cap the distal end of the rod. The Rigi10™ device has a reported 135-degree flexibility.The Rigi10™ malleable prosthesis is a relatively new device introduced in 2019.To date, there is no published study on the Rigi10 device.14 The cylinder rod is available in a single size of 11 mm in diameter and 12–25 cm in length that consists of an 8-m distal part (can be cut at 5 mm each), a 12-cm central part (bendable) and a 5-cm proximal part (can be cut at 10 mm each). In contrast, the unique Zephyr ZSI 100 female-to-male (FTM) malleable implant is designed specifically for trans males, and it has an adjustable distal end from 13 to 16 cm and a cylinder width of 22 mm. It has a separate 25 mm wide, glans-shaped ‘stopper’ that can be affixed to the distal tip of the implant while the proximal part is made of silicone and stainless steel for fixation onto the pubic bone. There is no information about the bending flexibility on both Zephyr malleable rods.In contrast to the previous three malleable implants produced in the United States, the Zephyr ZSI malleable implant series is produced by a European manufacturer. The Zephyr ZSI 100 malleable implant was introduced in 2020 and is made of a Nusil silicone cylinder with a reinforced inner plate Nitinol (Nickel–Titane) cable to ensure mechanical reliability and a flexible distal part for optimum gland comfort in a flaccid position. While the Zephyr ZSI 100 FTM was successfully placed in 24 transgender males following phalloplasty, it was associated with high complication rates in eight patients (32%), namely, prosthetic infection (n = 3), protrusion (n = 4) or pubic pain (n = 1), and an additional three patients had their prostheses explanted due to difficulty living with the malleable prosthesis. Of those with the prosthesis in place, 13 of 14 patients (93%) were able to engage in penetrative sexual intercourse.While there is no published data on the Zephyr ZSI 100  malleable implant, there is one study published on Zephyr ZSI 100 FTM malleable implant. It consists of a graded silicone elastomer ranging from soft hardness at the distal tip, medium hardness in the middle section and high hardness silicone in the proximal end . The distal two-thirds of the device is term functional length and consists of a polytetrafluoroethylene (PTFE)-covered silver twisted wire core to ensure axial rigidity yet provide up to 130 degrees of malleability for the distal component. Its proximal third has multiple 5 mm circular marks for trimming to the required length. Two rear-tip extender caps are available in 10 mm and 15 mm sizes. There is no information about the bending flexibility of this TUBE malleable device.The TUBE (Promedon) malleable prosthesis was marketed back in 2006. consisting of 83 patients reported successful sexual intercourse in 75 (90.4%) of cases and complaints of prosthesis too short were recorded in 27 (32.5%) patients. Common complications encountered include crural cross-perforation (4%), penile hematomas (1.6%) and penile hypoesthesia (0.8%). A larger study published almost a decade later by a different group on 128 patients showed an overall satisfaction rate of 78.5% with relatively low complication rates such as glans urethral injury (1.5%), acute urinary retention (3.9%), superficial wound infection (7%), penile discomfort (9.4%) and penile prostheses infection (5.5%).There are two studies published on Promedon TUBE prosthesis. An earlier study The latest Shah device consists of a silicon elastomer and has four parts, namely, a soft distal silicon tip, an anterior segment of very stiff silicon (for penile rigidity), a central 5 cm zone of soft silicon  and a moderately firm posterior crural segment that could be trimmed and fitted with rear-tip extenders. The Shah Penile Prosthesis is available in two models, namely, (1) with a hinge and (2) without a hinge. Both types and all sizes of prostheses are covered with two removable outer sleeves of silicone elastomer, which can be removed to adjust the diameter of the prosthesis (this minimizes the inventory).The first prototype of the Indian malleable penile implant was manufactured in 1996, and over the years, the Shah Indian penile prosthesis has evolved through many models. On the contrary, the Shah prosthesis without hinge is a semi-rigid implant with uniform stiffness that is adequate for intercourse while being flexible enough to permit concealment. It can be trimmed from the proximal end so that a single implant can be adjusted to any penile length. This device is available in two grades of firmness (hardness), namely, medium firm implant (known as a regular prosthesis) while the softer one  is often reserved for high-risk patients or difficult cases (to minimize the risk of extrusion).Shah prosthesis with hinge has a flexible central area that acts as a hinge to allow the penis to be bent for concealment when not in use. The distal one-third is made of firm silicone while the middle segment is made of soft silicone to provide a hinge effect, and the proximal one-third is made of medium-hard silicone . To date, three reports have been published with the Shah penile prosthesis; a single case report in a neophallus while the other study showed good residual penile tumescence in 50% of cases and more than 90% of patients reported no problem with device concealment. In another paper comparing Shah’s device and AMS 650 prostheses, there were no significant differences reported in the ED Inventory of Treatment Satisfaction (EDITS) questionnaire and EDITS partner survey at 80.66 ± 4.49 and 75.66 ± 6.57, respectively, at 12 months after surgery and 71.73 ± 8.10 and 65.6 ± 6.49, respectively, at 24 months after surgery. Major and minor postoperative complications were seen in 10.7%  and 21.4% (6/28) of patients, respectively.In contrast to the last five malleable devices, the sale of the Indian malleable penile implant is largely confined to the local Indian market only and costs considerably less compared with ‘Western’ malleable prostheses.2730 Finally, in patients compromised by infection or priapism, the rods can be successfully exchanged for an IPP later, with potentially longer and wider cylinders for a greater patient satisfaction rate.Over the past few decades, there have been numerous design and technological advancements to improve overall clinical efficacy, mechanical durability, axial rigidity and device concealability of malleable penile prostheses. While a malleable prosthesis will never match the ‘naturalness’ of an IPP, there are still certain situations and conditions in which the simplicity of a rod may be preferred over an inflatable device. A pair of malleable rods have been shown to have less risk of malfunction and need for revision surgery. Furthermore, a malleable prosthesis is significantly cheaper than an IPP, and this could play an important factor if the patient is not privately insured and would need to pay for the device. The implantation of a malleable prosthesis is easier and faster with minimal intraoperative device preparation. In addition, its role can be extended to patients with poor manual hand dexterity, those undergoing a salvage for infection prosthesis and as an emergency surgical measure in patients presenting with acute ischaemic priapism. with better axial rigidity, girth and bending flexibility for concealment. At this stage, there is no direct comparative study among these malleable prostheses in terms of clinical efficacy, mechanical durability or safety outcomes. Proper patient selection and strict counselling regarding what to expect with malleable prosthesis coupled with adherence to safe surgical principles are paramount to ensure excellent clinical success and patient satisfaction rates.Future research and development into the malleable device are likely to reside in more advanced materials such as the Nitinol exoskeleton


The first vulnerability framework for sustainability science was published about two decades ago. It embedded vulnerability analysis into the foundational lens of sustainability and resilience research – the social-environmental system (SES) – and called for an integration of the vulnerabilities of the social and environmental subsystems as opposed to the dominating attention given at the time to societal vulnerability. The framework recognised that the environment itself is vulnerable to disturbances and that the interactions of the two subsystems create a system-wide vulnerability central to questions of sustainability or sustainable development. It also provided multiple components of analysis that should be considered if vulnerability research and assessments were to contribute more fully to sustainability themes. Using bibliometric analysis and attention to subsequent vulnerability publications, various impacts of this original framework on vulnerability studies were examined in the study, including its recognition by citations, citation pathways and fields of study, and the degree to which its various dimensions were employed. It was found that its large citation recognition was not necessarily matched by attention to the dimensions the framework proposed, noting several exceptions.The authors interpreted this discrepancy to have followed from the analytical complexity fostered by the framework and to the significant proportion of vulnerability interests that was and remains focused on societal vulnerability as opposed to the social-environmental one, even in this moment in which sustainability in the Anthropocene has become a paramount query. The turn of the new millennium witnessed the formation of sustainability science  and environmental subsystems and their interactions. A full analysis would consider: (1) the multiple biophysical and social disturbances  to which the SES is exposed; (2) the sensitivity of the SES to that exposure, including its amplification or attenuation by the subsystem’s interactions; and (3) the coping (or adaptive) capacities of adjustments and adaptations of the two subsystems and their interactions. Feedbacks on disturbances, exposure and sensitivity occur throughout the VASS framework, and the outcomes have impacts on social and environmental phenomena and processes beyond the SES in question, which in turn affect the various dimensions of the VASS framework.These characterisations of VASS have been recognised in subsequent vulnerability reviews and assessments  have subsequently been developed, such as social vulnerability framings , leading to 222 publications. Lastly, the second author screened the titles and abstracts to remove papers that contain those terms yet are not empirical or do not use the term framework in relation to vulnerability. In the end, 175 papers were determined as eligible for thematic coding.Coding the 175 empirical papers involved consideration of 12 key features of VASS: (1) SES interaction; (2) feedbacks throughout the system; (3) vulnerability of the environmental or ecosystem subsystem; (4) multiple disturbances, both physical and social in kind; (5) attenuation or amplification of exposure or sensitivity due to subsystem interactions; (6) interactions of SESs or their phenomena and processes beyond the SES in question; (7) restructuring of SES after disturbance; (8) nonlinearity characteristics of the SES; (9) legacies in the system; (10) new vulnerability metrics or measures employed; (11) tests of the linkages in the system; and (12) approaches working backwards from unwanted outcomes to the disturbance. The second author read the full-texts of the papers to identify relevant information to determine the presence or not of the VASS-advanced features in the 175 papers. During the coding process, 28 papers were removed from the content analysis for irrelevance, leading to 147 coded papers. In addition, several papers included more than one case study, each of which was treated independently. As such, 157 cases in the 147 papers were examined regarding the VASS key features. In the process, feature 11 was revised from ‘test of linkages in the system’ to ‘the validation of the applied or newly developed vulnerability metrics or measures’ because almost none of the 157 cases explicitly tested the linkages in the system. Additionally, whether the studies were quantitative or qualitative-quantitative regarding the VASS-advanced dimensions was also coded. The first author coded 15 randomly selected papers out of the 147 papers (i.e. 10%) to cross-validate the coding reliability. The cross-validation by the first author produced an overall agreement of 96.16% and a Kappa Coefficient of 91.30%, indicating excellent inter-coder consistency.This article followed all ethical standards for research without direct contact with human or animal subjects.Nature, Science).The VASS paper received 1967 citations in the Scopus database from peer-reviewed English outlets published before 2021. These articles were published in journals covering the full spectrum of the 27 major subject areas indexed in Scopus 4. The hiTopics mined from the titles and abstracts of the 1967 VASS-citing papers add thematic details to the citation landscape of VASS. These details cluster into four main research themes : vulneraThe topic mining is supported by historiographical analysis of the 1967 VASS-citing papers based on their citation linkages . CitatioThe VASS-proposed SES vulnerability concept was applied conceptually between 2005 and 2007. It was variously addressed regarding such topics as adaptation Füssel , often tAll of 1967 VASS-citing papers do not necessarily address SES vulnerability as proposed by VASS, an observation supported by this study’s content analysis of the 157 coded cases (above). In fact, the majority of the 12 key VASS features for operationalising SES vulnerability have received inadequate attention to date . A signiA little over a quarter of these cases (28.66%) considered multiple disturbances, some addressing both physical  and social  ones. A similar proportion of the cases (28.03%) considered the restructuring of SES after disturbances. Working backwards from unwanted outcomes to disturbance(s) and accounting for nonlinearities and legacies were only considered, respectively, in 8.92%, 9.55% and 12.10% of the cases.Finally, over three-quarters (77.07%) of the cases were indicator-based assessments of regional, sectoral or social conditions that develop new vulnerability metrics or measures. Only 5.73%, however, attempted to validate or justify the reliability of such metrics, often by participatory judgement of indicator relevance or statistical alignment with participatory vulnerability ranking. In addition, very few of the coded studies elaborated cause-and-effect links, and almost none of them tested the links. Nonetheless, the dominance of indicator-based vulnerability assessments created a dominant quantitative approach ; 64.33%,In the first decade of the new century, sustainability emerged as a major field of study, with SESs as either the phenomena or means of study. VASS was framed within this context, elevating it to the forefront of vulnerability discussions. This visibility is registered not only in the 1967 carefully identified citations in the Scopus database but also by the more than doubling of that number in Google Scholar, which includes more than articles alone. Either database indicates visibility ranging across a wide assortment of research fields . The 196These three dimensions and the links among them appear as the most common VASS characteristics in the 157 cases of the 147 empirical vulnerability papers examined in detail in this study. Considering other articles, however, VASS-identified themes included: recognition of interactions with phenomena and processes beyond the immediate SES in question, feedbacks within and beyond the SES and attempts at fusing parts of resilience and vulnerability, especially in the context of sustainability problems  rationality as the base means of understanding knowledge   and external (e.g. stakeholder participation) validation is needed.The VASS effort assumed middle-range theory building (Turner et al.


To evaluate the effect of long-term rotation on astigmatism following Evolution-toric intraocular collamer lens (EVO-TICL) implantation.Forty eyes of 22 patients were enrolled in this prospective study. Visual acuity, refractive parameters, and axial position of the EVO-TICL by OPD-Scan III aberrometer were measured preoperatively, 1 month and 3 years postoperatively.p < 0.001). The expected astigmatism was −0.10 ± 0.12D, and the mean actual astigmatism was −0.21 ± 0.30D and − 0.44 ± 0.45D 1 month and 3 years postoperatively, respectively. The mean absolute rotation without postoperative astigmatism was 3.73 ± 2.69 (0–9°) and 1.67 ± 1.66 (0–5°) for low (<2D) and high (≥2D) astigmatic TICL, respectively (p < 0.05).Last visit, the safety index was 1.32 ± 0.15 and the efficacy index was 1.01 ± 0.23. The best-fitting curve of the attempted versus achieved correction was y = 0.9751x + 0.001. The mean spherical equivalent (SE) decreased from −8.94 ± 2.72D preoperatively to 0.06 ± 0.24D and − 0.36 ± 0.46D 1 month and 3 years postoperatively, respectively. The mean target and surgical induced astigmatism were 1.55 ± 0.61D and 1.67 ± 0.94D 3 years postoperatively. The average expected axis of the TICL was-1.15 ± 9.07 (−21–19°). One month and 3 years postoperatively, the average actual axis was −0.70 ± 9.86 (−20–20°) and − 0.35 ± 11.72 (−25–30°), respectively. The absolute rotation of the TICL was 3.70 ± 4.42 (0–22°) and 6.00 ± 6.70 (0–32°) 1 month and 3 years postoperatively, respectively (EVO-TICL implantation is safe and effective, with good predictability and stability. OPD-Scan is a fast device to detect the axial position of the TICL without mydriasis, and the axial position is relatively stable in the long term postoperatively. A slight rotation of low-astigmatic TICL may not cause postoperative astigmatism, whereas rotation of the high-astigmatic TICL may cause it. Myopia is a global health problem . SeveralEvolution-toric intraocular collamer lens , a posterior chamber phakic intraocular lens, has been widely used in recent years because of its wide range of correction of myopia and astigmatism, independent of corneal conditions. The safety, effectiveness, stability, predictability, and significant improvement in postoperative visual quality have been reported previously , 6. AccuThis prospective study was approved by the Ethics Committee of Fudan University Eye, Ear, Nose, and Throat Hospital. Patients participated voluntarily and signed an informed consent form. This study included 40 eyes of 22 patients who underwent EVO-ICL implantation. The male-to-female ratio was 3:19, the average age was 24.82 ± 4.32 (18–33) years old, the preoperative equivalent spherical lens was −8.94 ± 2.72 (−1.38–15.75) D, and the preoperative average cylindrical lens was −1.60 ± 0.61 (−0.75–3.00) D .2, (5) astigmatism ≥0.75 D.The inclusion criteria were as follows: (1) patients stopped wearing contact lenses for >1 week preoperatively, (2) the refraction was basically stable, with an annual growth of <0.50 D for at least 2 years, (3) the anterior chamber depth (ACD) was >2.8 mm, (4) the endothelial cell density was >2000 cells/mmThe exclusion criteria were as follows: (1) eye inflammation, obvious refractive interstitial opacity, previous eye surgery, glaucoma, cataract, and other eye diseases, (2) systemic connective tissue and autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and diabetes, (3) patients with mental or psychological abnormalities and unrealistic expectations.Observation indicators and follow-up: Uncorrected distance visual acuity (UDVA), corrected distance visual acuity , refraction , ocular axis , intraocular pressure , endothelial cell density , vault , TICL axis , and 3-year follow-up. Each measurement was performed thrice by experienced technicians.OPD-Scan III  was used to measure patients with TICL implantation preoperatively, 1 month postoperatively, and 3 years postoperatively, and to record the axial position of the TICL in the eye within serveral seconds without mydriasis. Using the image obtained by OPD-Scan III, the axis position was adjusted to be parallel to the TICL axis position, and the angle between the adjusted axis position and the calibration axis was calculated to determine the TICL axis position . Each meAll surgeries were performed with standard practice by the same surgeon (XW). The implanted intraocular lens was EVO-TICL, the optical area was 4.9–5.8 mm, the spherical lens power range was −0.5 to −18.0 D, and the cylindrical lens power range was +0.5 to +6 D. Four sizes were available: 12.1, 12.6, 13.2 and 13.7 mm.Anti-inflammatory eyedrops were administered 3 days preoperatively. The mydriasis was started 30 min before ICL implantation, surface anesthesia was given to the operative eye, the cloth was disinfected routinely, the eyelid opener was used to open the eyelid, and a 3.0 mm corneal incision was made at the temporal corneoscleral margin. The special injector implanted the ICL in the crystal chamber into the eye. After the ICL unfolded naturally, a special positioning hook was used to adjust the haptics to the back of the iris. Postoperatively, the patients were administered the steroid drug brigitte  qid * 3 days; antibacterial drugs  qid * 1 week; non-steroidal anti-inflammatory drugs  qid * 2 weeks; and artificial tear, qid * 1 month.p < 0.05 was considered statistically significant.SPSS 26.0  was used to analyze the data. The Kolmogorov–Smirnov test was used to test the normal distribution of data and repeated-measures analysis of variance was used to compare the data at various time points pre- and post-operatively. Also, a paired t-test was used to compare the parameters in the early and long postoperative period, and an independent sample t-test was used to compare low-and high-astigmatic TICL. Continuous variables were expressed as mean ± standard deviation. Forty eyes of 22 patients with preoperative manifest spherical equivalent (SE) and cylinder of −8.94 ± 2.72 and − 1.60 ± 0.61 D were included. Their mean age was 24.82 ± 4.32 (18–33) years. The preoperative data for the two groups are listed in Three years postoperatively, UDVA was −0.01 ± 0.13 logMAR (range: −0.18–0.40 logMAR) and the efficacy index (postoperative CDVA/preoperative CDVA) was 1.01 ± 0.23. After 3 years, 97.50 and 65.00% of the eyes achieved UDVA of 20/40 and 20/20 or better, respectively . Figure p < 0.001). Three years postoperatively, CDVA was −0.13 ± 0.06 logMAR (range: −0.18–0.10 logMAR) and the safety index (postoperative CDVA/preoperative CDVA) was 1.32 ± 0.15. A significant increase was observed from the preoperative to the postoperative CDVA (A scatter plot with the best-fit line of the attempted versus the achieved SE correction is shown in p < 0.05).The manifest SE decreased from −8.94 ± 2.72 D preoperatively to 0.06 ± 0.24 D at 1 month and − 0.36 ± 0.46 D at 3 years postoperatively . The difAfter 3 years, the manifest cylinder was −0.44 ± 0.45 D (range: -2.00–0.00 D) and 75% of eyes were within −0.50 D . Using Ap < 0.001). The proportions of absolute rotation angles above 15° at 1 and 3 years postoperatively were 2.5 and 7.5%, respectively. Clockwise rotation occurred in 35.0 and 42.5% of eyes, counterclockwise rotation occurred in 42.5 and 47.5% of eyes, and no rotation occurred in 22.5 and 10% eyes at 1 month and 3 years postoperatively, respectively, compared to the baseline (p > 0.05). The mean attempted cylindrical refractive error was −0.10 ± 0.12 D and the mean achieved cylindrical refractive errors were − 0.21 ± 0.30 D and − 0.44 ± 0.45 D at 1 month and 3 years postoperatively, respectively.p < 0.05), respectively. The ranges were 0–9° and 0–5°, respectively.In this prospective study, we analyzed the visual and refractive outcomes after implantation of a EVO-TICL in 40 eyes of 22 patients. We demonstrated that the EVO-TICL is predictable, safe, and effective for correcting low and high levels of astigmatism. Furthermore, EVO-TICL showed promising results in terms of postoperative rotational stability. Although several articles –14 have The present study’s safety and efficacy indices were 1.32 and 1.01, respectively, which indicates that TICL implantations offer excellent safety and efficacy in the long term postoperatively. Previous research reported a postoperative safety index of 1.22 and an efficacy index of 1.03 at the 4-year follow-up , which iThe refractive outcomes in this study showed satisfactory predictability. Three years postoperatively, 78.00 and 95.00% of eyes were within ±0.50 D and ± 1.00 D of emmetropia, respectively, and conformed with previous research . The manThe rotational stability of the toric ICL is a crucial factor for achieving high efficacy in the correction of astigmatism. In our study, the absolute degree of rotation at 1 month postoperatively was 3.70 ± 4.42°, which is comparable to that obtained in recent studies evaluating the EVO-TICL  . The patients/participants provided their written informed consent to participate in this study.XC, HM, MC, I-CL, BL, YJ, YL, XW, and XZ involved in the conception or design of the work, the acquisition, analysis or interpretation of data for the work and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. XC and HM drafted the work or revising it critically for important intellectual content. XW and XZ final approval of the version to be published. All authors contributed to the article and approved the submitted version.This study was supported by National Natural Science Foundation of China (grant nos. 81770955 and 82171095), Project of Shanghai Science and Technology (grant nos. 20410710100 and 19140900700), Clinical Research Plan of SHDC (grant no. SHDC2020CR1043B), Project of Shanghai Xuhui District Science and Technology , Shanghai Engineering Research Center of Laser and Autostereoscopic 3D for Vision Care (grant no. 20DZ2255000), Construction of a 3D digital intelligent prevention and control platform for the whole life cycle of highly myopic patients in the Yangtze River Delta (grant no. 21002411600).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Heart failure with preserved ejection fraction accounts for a large proportion of heart failure, and it is closely related to a high hospitalization rate and high mortality rate of cardiovascular disease. Although the methods and means of modern medical treatment of HFpEF are becoming increasingly abundant, they still cannot fully meet the clinical needs of HFpEF patients. Traditional Chinese medicine is an important complementary strategy for the treatment of diseases in modern medicine, and it has been widely used in clinical research on HFpEF in recent years. This article reviews the current situation of HFpEF management, the evolution of guidelines, the clinical evidence and the mechanism of TCM in the treatment of HFpEF. The purpose of this study is to explore the application of TCM for HFpEF, to further improve the clinical symptoms and prognosis of patients and to provide a reference for the diagnosis and treatment of the disease. Heart Failure Society of America (AHA/ACC/HFSA) guidelines in 2022, heart failure is divided into four categories: heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF), heart failure with midrange ejection fraction (HFmrEF) and heart failure with improved ejection fraction (HFimpHF) (Heart failure (HF) with preserved ejection fraction (HFpEF) refers specifically to left ventricular ejection fraction (LVEF) ≥ 50%. It is a syndrome that accumulates in multiple organs and systems. The main clinical manifestations are exertional dyspnoea and exercise intolerance. According to the latest American Heart Association/American College of Cardiology/HFimpHF) . AccordiHFimpHF) , while HHFimpHF) . The risHFimpHF) . The disHFimpHF) . TherefoHFimpHF) .The 2022 AHA/ACC/HFSA guidelines proposed guideline-directed management and therapy (GDMT) as the cornerstone of drug treatment, and SGLT2i, MRA, and ARNI are included in the recommended drugs according to the guidelines. However, a one-size-fits-all treatment strategy has difficulty solving the real problem. For example, the risk period for HFrEF requires initiating drugs to prevent disease progression, while there is a lack of treatment strategies for the risk period for HFpEF. Given the high mortality and rehospitalization rate of HFpEF , how to In the past, HFpEF was regarded as an early stage of the transition to HFrEF. Modern research shows that the transition from HFpEF to HFrEF is rare. Compared with HFrEF, HFpEF has higher comorbidity and noncardiovascular mortality . TherefoAt present, HFpEF lacks a specific diagnostic test. Although Doppler echocardiography can support the diagnosis of HF through evidence such as increased ventricular filling pressure or decreased cardiac output, it cannot support the diagnosis of HFpEF (it cannot reflect LVEF or cardiac morphology) . When ph2, mitral E velocity >90 cm/s, septal e’ velocity <9 cm/s, and E/e’ ratio >9  improving the TCM symptoms and the exerting a curative effect on TCM syndrome; improving the quality of life, anxiety, depression, and fatigue of patients, including the MLHFQ score, SAS score, SDS score, and FS-14 score; 2) enhancing tolerance of daily activities and improving cardiopulmonary motor function, including NYHA grade, Lee’s heart failure score, 6-min walk test (6 MWT) and cardiopulmonary exercise test (CPET); 3) strengthening cardiac pumping function, improving systolic and diastolic function, reducing myocardial oxygen consumption, and improving coronary artery circulation. By improving parameters echocardiography such as E/e', E/A, LAVI, LVEF and LVMI, regulating left ventricular systolic function and systolic synchrony by adjusting STI parameters such as |GLS| and UT, and improving haemodynamics by increasing the CI and SI index; and 4) maintaining intravascular homeostasis, including reducing sST2 and hs-CRP to improve systemic inflammation; reducing CRP, IL-1β, IL-6, and other inflammatory factors and decreasing ET, TGF-β1, TNF-α, and AngII to control myocardial fibrosis and left ventricular hypertrophy; improving blood fat and blood pressure, such as total cholesterol (TC) and diastolic blood pressure; improving endocrine metabolism, including by increasing oestrogen E2 levels, interfering with insulin resistance, and reducing Homa-IR and FINS; reducing BNP and NT-proBNP to improve prognosis; and lowering mortality and rehospitalization rates, and preventing the development of HFpEF.There is no unified conclusion on the specific mechanism of HFpEF. At present, it is widely believed that it is a multisystem disease involving the heart, lung, kidney, skeletal muscle, adipose tissue, immune/inflammatory signals, and vascular system . AccordiAt present, three main haemodynamic mechanisms of HFpEF are observed according to the cardiac ultrasound parameters and the improvement of BNP and NT-proBNP.As HFpEF was originally named after diastolic heart failure, most of the experimental studies in this paper have improved the problem of left ventricular diastolic dysfunction by regulating parameters such as E/e', E/A, LVEDP, BNP, and NT-proBNP. For example, Yiqihuoxue decoction  can imprPulmonary vascular disease and right ventricular dysfunction are rare, the prognosis is poor, and the mortality is high . Shenfu The expansion of plasma volume is mainly related to right heart dilatation and total cardiac volume expansion. Shengmai decoction , Qishen The comorbidity of HFpEF leads to systemic microvascular inflammation, including circulatory inflammation, myocardial inflammation, extracardiac organ inflammation , and diseases associated with inflammation (such as obesity and hyperlipidaemia).The problems caused by systemic microvascular inflammation include endothelial dysfunction, oxidative stress, and decreased bioavailability. Experimental research shows that the TCM YangxinNo.2 Granules , Shenfu 2+. Low availability of cGMP leads to low expression of PKG, inhibition of titin phosphorylation, and decreased myocardial compliance. On the one hand, TCM improves oxidative stress: Nuanxin capsule  abnormal structure and function of mitochondria, 2) changes in substrate utilization, and 3) intracellular calcium overload. The structural and functional abnormalities of mitochondria are reflected in organelle dyspnoea, shrinkage, enlargement, a decrease in membrane potential, and other problems, resulting in a decrease in ATP synthesis. Due to the change in mitochondrial function and structure, the utilization of substrate changes accordingly, the heart changes from fatty acid metabolism to glucose metabolism, glucose oxidation decreases, glucose degradation occurs, and lactic acid increases. At the same time, SERCA2a deficiency eventually leads to intracellular calcium overload.2+ overload. In addition, they can inhibit RyR2 and CaMKII to reduce the release of Ca2+, and inhibit ERK1/2, leading to downregulation of GATA4 and improvement of BNP.Experimental studies have shown that the TCM Nuanxin capsule , Shenfu PKG, cGMP, and Titin phosphorylation in cardiomyocytes jointly regulate myocardial contractile motion, and the high expression of Titin in cardiomyocytes reflects the decrease in Titin phosphorylation. TCM Fuzibanxia decoction , TongmaiStructural abnormalities of myocardial extracellular matrix (ECM), including fibrosis and amyloid protein, can occur. ECM mainly depends on the balance of MMPs and TIMPs. If the balance is lost, myocardial fibrosis will occur. In addition, TGF-β/Smads, p38MAPK, the G protein-coupled receptor kinase (GRK) signal pathway, and TGF-β1 expression induced by AngII can all lead to the development of fibrosis. TCM Shenfu decoction , LingguiThe number of deaths caused by HFpEF worldwide is gradually increasing every year, and increasing attention has been given to the prevention and treatment of HFpEF. Western medicine treatment can control the development of HFpEF, but it still faces the bottleneck problem. While developing new drugs and devices, modern medicine has recognized the individual treatment advantages and overall regulatory effects of TCM.At present, the integration of traditional Chinese and Western medicine has become an objective and generally accepted medical model in the treatment of HFpEF. TCM treatment can improve the clinical symptoms of HFpEF, enhance the quality of life of patients, lower the poor prognosis of patients, reduce mortality and rehospitalization rates, and provide new ideas and methods for the treatment strategy of HFpEF. However, due to the diversity of TCM syndrome types and the strong subjectivity of dialectical analysis, TCM lacks certain convincing power in the process of development. The relationship between TCM and botanical drugs lacks a rigorous scientific research system, and the relationship between the ‘monarch’ and ‘minister’ in the compound prescription of TCM is seldom discussed. In addition, most of the studies on the treatment of HFpEF with TCM have a small sample size, short observation time, and lack of rigor in design. Therefore, the research results cannot be widely applied and popularized. In the future, research on TCM in the treatment of HFpEF should start from the following three angles 1) In terms of theory, it is convenient to distinguish syndrome types by setting an objective threshold for dialectical analysis. The purpose of the research is to analyse the relationship between the existing compound prescriptions of TCM and botanical drugs. 2) From a clinical perspective, we need to standardize the clinical design; perform large-sample, multicentre randomized clinical controlled trials; enhance the observation and follow-up time; and evaluate the effectiveness and safety of TCM on HFpEF. 3) In terms of experiments, people should identify the subtypes of HFpEF and expand different modelling methods to consider different mechanisms of TCM treatment to provide new ideas for improving HFpEF.In summary, HFpEF is still a thorny clinical disease. TCM has great potential for HFpEF. However, more extensive and rigorous clinical and animal experiments are needed to promote the application of TCM in HFpEF.


Immunization information systems (IIS) are confidential, population-based computerized databases that record vaccination doses administered to persons residing within a given geopolitical area. We sought to highlight the evolution of IIS policy over the last two decades, as IIS play a pivotal role in achieving equitable and high vaccine uptake.Legal epidemiological research methods were used to assess relevant IIS statutes and administrative codes across all 50 states, the District of Columbia, Philadelphia, and New York City. Where relevant, laws were cross-checked or supplemented with state and local health department resources. Comparisons to previous legal studies enabled evaluation of trends in IIS laws over time.The compilation of current laws provides an updated overview of the diverse interstate and intrastate policies within the US that govern the capabilities and implementation of IIS. The findings of this study show the progress that has been made in the past decade in improving policies that enable IIS to be utilized across the life-course. Conversely, gaps in IIS data collection, limited interoperability with local and national health information systems, and inconsistent access to view or utilize IIS records due to existing policies, continue to limit the full potential of IIS.In the United States (US), IIS are implemented and managed at the state and local level, creating variability in IIS policies and implementation. Findings from this study serve as a comprehensive benchmark of current IIS laws that may aid policy stakeholders who are exploring amendments to jurisdictional IIS laws.The online version contains supplementary material available at 10.1186/s12889-023-16457-2. Immunization information systems (IIS) are confidential, population-based, computerized databases that record, consolidate, and report vaccinations administered by participating providers to persons residing within a given geopolitical area . The COVCurrently, in the US, IIS are operated at the jurisdictional level with no national centralized repository for vaccination data. There are over 60 different state, tribal, city, and territorial IIS . DisparaA comprehensive legal assessment of IIS laws has not been completed since 2012 . The objWe used legal epidemiological research methods  to compl® legal database and underwent a series of validations with independent coders reviewing each coding decision from August 2021 to February 2022.Each jurisdiction’s laws were divided among five independent coders for analysis and coded against the legal variables. A minimum of two independent reviewers conducted an evaluation and validation of the final dataset values with the support of state sources such as jurisdiction health department websites. Independent evaluators reviewed all coding decisions to ensure accuracy and quality. Discrepancies were identified and aligned upon by a minimum of three reviewers for final coding decisions. We also identified whether there were ambiguities in the law which precluded coding decisions. Across our coding questions, if the law was silent on a particular coding attribute, we coded it to indicate that the attribute was not mentioned.Active state laws were collected between July 5th and July 16th, 2021, using the WestlawNextAnalyses of legal data were conducted from August 2021 to February 2022. Data was collated using Microsoft Excel and geographical maps were produced using JMP (version 15.2.0). See online supplemental materials for a complete jurisdiction-based coding table  required all or certain providers to report all pediatric vaccinations to the IIS Table B. Of theThere was variability in the types of providers required to report pediatric vaccinations to the IIS. Twenty-eight states, NYC, and PHI (57%) required all providers to report pediatric vaccinations to the IIS; in contrast, six jurisdictions (11%) only required pharmacists to report. The remaining eight jurisdictions (15%) required specific provider types to report pediatric vaccinations or had requirements for only select vaccines. For example, under CA law, pharmacists and optometrists must report vaccinations to the IIS . On the Thirty-five states, DC, NYC, and PHI (72%) required some provider reporting of adult vaccination to the IIS. Nineteen states and PHI (38%) required all providers to report adult vaccinations to the IIS Table B. Six stSeven jurisdictions 13%) expressly included penalties to encourage compliance with provider reporting requirements. Penalties across these jurisdictions varied from monetary penalties and vaccine ordering restrictions to referral to the relevant licensing board or removal from the VFC program. For example, AR law stated that “[f]ailure to report shall result in the Department contacting the Provider to encourage compliance. Continued non-compliance may result in sanctions not to exceed $25.00 and/or removal from the Vaccine For Children (VFC) program” . Under M3% expresIn 14 states and NYC (28%), pediatric data was included in the IIS and the law did not mention patient or parent/guardian ability to “opt-out” or remove their data from the IIS (Table Three states (6%) required consent for pediatric data to be reported into the IIS, while in 7 states and DC 15%), the law was ambiguous or silent as it relates to consent. Written consent is required in MO and TX, whereas MT law did not specify that consent must be written. For example, under MO law, “[t]he patient shall attest to the inclusion of such information in the system by signing a form provided by the pharmacist” . Unlike 5%, the lRegarding inclusion of adult vaccination data in the IIS, nine states’ laws 17%) did not specify that patients could “opt-out” or remove their data from the IIS; in eight states and DC (17%), the law was ambiguous or silent as it relates to consent (Table 7% did noThirty-nine states and NYC (75%), expressly reference intrastate data sharing. This is data sharing that includes an exchange of data between the IIS and other data systems within the state and may specify entities, persons, or reasons for information sharing. For example, WV law provided a detailed list of permitted disclosures including how the data should be used and by which entities, such as local health departments, licensed providers, and school officials, among others  states’ laws expressly identified interstate data-sharing permissions, or data exchange across state lines. States may share data across states through broader public health data sharing provisions (similar to intrastate provisions), which may not be captured in this analysis if the laws did not expressly reference IIS data-sharing. Per ME law, “[t]he Department may exchange information with other immunization registries and/or immunization databases maintained by health maintenance organizations and health insurance companies” . SimilarForty-one states, DC, and NYC 81%) expressly stated that the IIS or an official copy of records obtained from the IIS was valid proof of vaccination for school or childcare entry (Table % expressForty-four (83%) jurisdictions allowed school or childcare personnel direct access to the IIS, meaning that personnel are users of the IIS system and are at least able to view records Table Twenty-two (42%) jurisdictions allowed write/edit access of IIS records to school and childcare personnel Table C. For exJurisdictional law may dictate that certain patient demographic data are required elements to report into the IIS; although, jurisdictions may collect additional demographic data beyond what is expressly required by law. Thirty states, DC, NYC, and PHI 62%) expressly identified certain required demographic data that must be included in the IIS Table D. There % expressTwenty-three states, DC, NYC, and PHI (49%) expressly required a current address as a data element in the IIS. Under NJ law, “[h]ealth care providers shall report. . the following required data fields. . : 1. Complete name; 2. Date of birth; 3. Ethnicity/Race; 4. Gender; 5. Address. . .” . This isSixteen states, DC, and NYC (34%) allowed patients or a patient’s parents or guardians direct access to view their records from the IIS through an online portal or mobile application Table E. Three This was the first comprehensive legal assessment of IIS laws within the US since 2012, to the authors’ knowledge . This stThe CDC has identified three broad user types and corresponding functions for IIS records: 1) patients and/or the patient’s guardian use of IIS information to determine their vaccination needs and to show proof of vaccination; (2) health care providers use of IIS at the point of clinical care to determine appropriate vaccinations during a patient visit; and (3) public health officials use of IIS to get aggregate population-level data for surveillance and program development . The fin patientsAnother important gap identified was direct access for patients to view their vaccination records in the IIS, which can empower patients or patient guardians to make informed decisions about their health. Direct access to an IIS also offers patients the ability to provide proof of required vaccination, without requesting them through a vaccination provider or public health professional. Despite the value provided by allowing for patient access, only 34% of jurisdictions provide patients direct access to view their own vaccination data from the IIS Table E.Additionally, increasing IIS interoperability with Electronic Health Record (EHR) systems and intrastate and interstate data sharing can help improve surveillance and reduce data quality challenges . Before Immunization information systems can also have a direct impact on vaccinations at the point of care by notifying patients that they are due for vaccinations and by supporting providers in determining appropriate vaccinations; preventing both over- and under- vaccination , 23. IISFurthermore, IIS records guide public health action. Public health officials and researchers use IIS to understand vaccination coverage, examine vaccination disparities, develop targeted vaccination efforts, and assess vaccination efficacy when vaccine-preventable diseases are present in a community . The CDCThe COVID-19 pandemic has exposed gaps in current vaccination data systems but has also created opportunities to modernize IIS infrastructure and legal frameworks, given the increased attention from policymakers and additional federal funding. Privacy, consent, and access continue to be consistent themes in IIS policy, especially in the context of the COVID-19 pandemic. These considerations must be weighed along with the essential need for IIS that are able to manage patient records efficiently and effectively and securely exchange information among states, across providers, and public health agencies to support vaccination efforts. Policymakers and public health stakeholders can also leverage behavioral economics and experience design when updating IIS laws and systems to increase participation and the inclusion of the broader population .This study was a comprehensive legal assessment of IIS laws with supplementary data from state health department websites. It did not include surveys or interviews of relevant jurisdictions operating an IIS. There may be programmatic policies in places that impose additional requirements that have not been included in this analysis. Local rules, policies, and municipal ordinances were not used unless incorporated within jurisdiction’s law or health department websites. Given rapidly evolving policy landscape due to the COVID-19 pandemic, some laws may have changed since the date of data collection.Immunization information systems are critical tools that support a robust and resilient vaccine ecosystem and broader health system infrastructure . They seAdditional file 1.