Objective: To fabricate a hydrogel loaded with inositol hexaphosphate-zinc and preliminarily evaluate its performance in self-mineralization and osteoinduction, thereby providing a theoretical basis for the development of bone regeneration materials. Methods: The hydrogel framework (designated DF0) was formed by copolymerizing methacryloyloxyethyltrimethylammonium chloride and four-armed poly(ethylene glycol) acrylate, followed by sequentially loading inositol hexaphosphate anions via electrostatic interaction and zinc ions via chelation. The hydrogel loaded only with inositol hexaphosphate anions was named DF1, while the co-loaded hydrogel was named DF2. The self-mineralization efficacy of the DF0 , DF1 and DF2 hydrogels was characterized using scanning electron microscopy, transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and selected area electron diffraction (SAED). The biocompatibility was assessed via live/dead cell staining and a CCK-8 assay. The osteoinductive capacity of the DF0 , DF1 and DF2 hydrogels on MC3T3-E1 cells was assessed via alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining. In the aforementioned cell experiments, cells cultured in standard medium served as the control group Results: The DF0, DF1, and DF2 hydrogels were successfully synthesized. Notably, DF1 and DF2 exhibited distinct self-mineralization within 6 days. Results from TEM, EDS, and SAED confirmed that the mineralization products were amorphous calcium phosphate in group DF1, and amorphous calciumzinc phosphate in group DF2. Biocompatibility tests revealed that none of the hydrogels (DF0, DF1, and DF2) adversely affected cell viability or proliferation. In osteogenic induction experiments, both ALP and ARS staining were intensified in the DF1 and DF2 groups, with the most profound staining observed in the DF2 group. Conclusion The developed inositol hexaphosphate-zinc hydrogel (DF2) demonstrates the dual capacity to generate calcium-phosphate compounds through self-mineralization while exhibiting excellent osteoinductive properties. This biocompatible, dual-promoting osteogenic hydrogel presents a novel strategy for bone regeneration.

Employing bibliometric methods and adhering to principles of textual research， this study systematically investigated prescription source， formula name， composition evolution， dose evolution， origin， processing， ancient and modern applications of Xiaofengsan. Xiaofengsan， also known as Renshen Xiaofengsan and Chantui Xiaofengsan， was first recorded in the Taiping Huimin Hejijufang（hereafter referred to as Jufang） of the Southern Song dynasty. The formula composition included Schizonepetae Spica， Glycyrrhizae Radix et Rhizoma， Chuanxiong Rhizoma， Notoptery Rhizoma et Radix， Bombyx Batryticatus， Saposhnikoviae Radix， Poria， Cicadae Periostracum， Pogostemonis Herba， Ginseng Radix et Rhizoma， Magnoliae Officinalis Cortex and Citri Reticulatae Pericarpium， a total of 12 medicinal materials. In terms of the evolution of formula composition， formulas across dynasties largely aligned with those recorded in Jufang， with only minor variations in application. The results of the formula dosage research indicated that one dose of medication in Jufang corresponded to the following modern dosages：Schizonepetae Spica of 82.6 g， Glycyrrhizae Radix et Rhizoma of 82.6 g， Chuanxiong Rhizoma of 82.6 g， Notoptery Rhizoma et Radix of 82.6 g， Bombyx Batryticatus of 82.6 g， Saposhnikoviae Radix of 82.6 g， Poria of 82.6 g， Cicadae Periostracum of 82.6 g， Pogostemonis Herba of 82.6 g， Ginseng Radix et Rhizoma of 82.6 g， Magnoliae Officinalis Cortex of 20.65 g and Citri Reticulatae Pericarpium of 20.65 g， the origins of all the constituent drugs were consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. The results of the investigation into the decoction method indicated that the aforementioned drugs should be finely ground into powder（pass through the No.5 sieve）， and 8.26 g was taken for each dose， which was taken with the clear liquid obtained by steeping tea leaves in boiling water for several minutes. This mixture was administered three times daily， 30 min after meals. The ancient functional indications of this formula mainly involved dispelling wind-heat， eliminating pathogenic factors and regulating the middle Jiao. It primarily treated all wind-heat syndromes manifesting as skin diseases， predominantly affecting the upper body， especially the head and face. The diseases involved in modern applications were mostly dermatological diseases， including urticaria， eczema， atopic dermatitis and others. In this paper， by combing the relevant ancient literature， the key information of Xiaofengsan was textual researched， in order to provide reference for the modern application and development of this formula.

Background/Aims: Obesity is associated with several gastrointestinal (GI) disorders and has been identified as a potential risk factor for various GI symptoms. Bowel frequency is an important indicator of bowel function. However, the causal link between obesity and gastrointestinal motility remains uncertain. This study aims to determine the causal effect of overall and central obesity on stool frequency. Methods: Four obesity-related anthropometric indicators–body mass index, body fat percentage, waist circumference (WC), and waist-tohip ratio (WHR)–were investigated. Individual-level baseline information from the UK Biobank was used to explore observational associations between obesity and stool frequency. Additionally, summary-level data from published genome-wide association studies were subjected to two-sample Mendelian randomization (MR) analyses to examine causal associations. Results: For all 4 indicators of obesity, higher levels of obesity were associated with more frequent bowel movements after adjusting for demographic characteristics, lifestyle, and dietary factors. After rigorous screening, 482 body mass index single nucleotide polymorphisms (SNPs), 7 body fat percentage SNPs, 48 WC SNPs, and 287 WHR SNPs were identified as instrument variables for MR analysis. The MR results were generally consistent with observational findings, proving that the associations observed in the overall obesity indicators were causal. For central obesity, the association between WHR and stool frequency remained consistent in both analysis phases, whereas WC showed a multidirectional association. Conclusions Obesity-related anthropometric indicators were causally associated with increased stool frequency in the overall and central obesity groups. Weight loss could be a potential approach to improve gastrointestinal regularity in individuals with obesity.

Objective To compare the differences in the average transaction costs per-referral patients under different models of Integrated Delivery Systems(IDS).Methods Using a typical case sampling method,it selected referred patients from three IDS models:the county medical alliance in D City(Qinghai Province),the urban medical consortium in J District(Zhengzhou City,Henan Province),and the health management coalition in N County(Shandong Province).Structured questionnaires collected demographics,average transaction costs per-referral and cost perceptions.t-tests and ANOVA assessed cost differences;generalized linear regression identified influencing factors.Results Among 915 patients,the average transaction costs per-referral were 1 035.05 yuan(county alliance),195.31 yuan(urban consortium),and 700.97 yuan(health management coalition),with statistically significant differences(P＜0.05).The urban consortium exhibited lower time costs and specialized input costs.Key influencing factors included older age(county alliance),education level,employment status,and referral travel time(urban consortium),as well as urban-rural disparities(health management coalition).Patients'cost perceptions significantly differed across models(P＜0.05).Conclusion The urban medical consortium demonstrated the lowest patient the average transaction costs,highlighting its institutional advantage in minimizing financial burdens.

Objective To investigate the effect of remimazolam(Rem)on retinal ischemia-reper-fusion injury(RIRI)in rats and its regulatory mechanism on the high-mobility group box 1(HMGB1)/receptor for advanced glycation end products(RAGE)/nuclear factor-κB(NF-κB)signaling pathway.Methods Rats were randomly divided into Sham group,Model group,Rem-L group(low-dose Rem),Rem-M group(medium-dose Rem),Rem-H group(high-dose Rem),and high-dose Rem plus HMGB1 activator dexamethasone(DEX)group(Rem-H+DEX group),with 15 rats in each group.Except for the Sham group,RIRI model was established in the other groups by increasing in-traocular pressure.Hematoxylin and eosin(HE)staining was used to observe the changes in retinal tissue structure in each group.The TUNEL method was used to detect retinal tissue apoptosis.En-zyme-linked immunosorbent assay(ELISA)was performed to detect the expression levels of interleu-kin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)in the serum of rats in each group.Kits were used to detect the levels of oxidative stress indicators,including superoxide dis-mutase(SOD),glutathione peroxidase(GSH-PX),and malondialdehyde(MDA).Western blot was used to detect the expression levels of hypoxia-related factors[hypoxia-inducible factor-1α(HIF-1α),vascular endothelial growth factor(VEGF)]and HMGB1/RAGE/NF-κB signaling pathway-related proteins in retinal tissue.Results Compared with the Sham group,the Model group showed severe retinal edema,a significant decrease in the number of ganglion cells,vacuolar changes in cells with disordered arrangement,and widened cell gaps.With increasing doses of Rem,the degree of retinal edema gradually decreased,the number of ganglion cells increased,and their arrangement became more orderly in RIRI rats.Compared with the Sham group,the Model group exhibited increased ret-inal cell apoptosis rate,serum levels of IL-1 β,IL-6,and TNF-α and increased expression levels of MDA,HMGB1,RAGE,NF-κB,HIF-1α and VEGF in retinal tissue,while the expression levels of SOD and GSH-PX decreased(P＜0.05).Compared with the Model group,the Rem-L,Rem-M,and Rem-H groups showed dose-dependent decreases in retinal cell apoptosis rate,serum levels of IL-1 β,IL-6,and TNF-α,and expression levels of MDA,HMGB1,RAGE,NF-κB,HIF-1α and VEGF in retinal tissue,with dose-dependent increases in the expression levels of SOD and GSH-PX(P＜0.05).Compared with the Rem-H group,the Rem-H+DEX group showed reversed trends in the above indicators.Conclusion Rem can inhibit the occurrence of RIRI in rats,and its mecha-nism of action may be related to the regulation of the HMGB1/RAGE/NF-κB signaling pathway.

Background/Aims: Obesity is associated with several gastrointestinal (GI) disorders and has been identified as a potential risk factor for various GI symptoms. Bowel frequency is an important indicator of bowel function. However, the causal link between obesity and gastrointestinal motility remains uncertain. This study aims to determine the causal effect of overall and central obesity on stool frequency. Methods: Four obesity-related anthropometric indicators–body mass index, body fat percentage, waist circumference (WC), and waist-tohip ratio (WHR)–were investigated. Individual-level baseline information from the UK Biobank was used to explore observational associations between obesity and stool frequency. Additionally, summary-level data from published genome-wide association studies were subjected to two-sample Mendelian randomization (MR) analyses to examine causal associations. Results: For all 4 indicators of obesity, higher levels of obesity were associated with more frequent bowel movements after adjusting for demographic characteristics, lifestyle, and dietary factors. After rigorous screening, 482 body mass index single nucleotide polymorphisms (SNPs), 7 body fat percentage SNPs, 48 WC SNPs, and 287 WHR SNPs were identified as instrument variables for MR analysis. The MR results were generally consistent with observational findings, proving that the associations observed in the overall obesity indicators were causal. For central obesity, the association between WHR and stool frequency remained consistent in both analysis phases, whereas WC showed a multidirectional association. Conclusions Obesity-related anthropometric indicators were causally associated with increased stool frequency in the overall and central obesity groups. Weight loss could be a potential approach to improve gastrointestinal regularity in individuals with obesity.

Objective:This study aimed to investigate the role of heat shock protein family A member 5 (HSPA5) in ferroptosis at its regulatory mechanisms in ulcerative colitis (UC), using both a dextran sulfate sodium (DSS)-induced mouse model of acute colitis and in vitro cell experiments.Methods:Differentially expressed genes in UC were identified using the GSE87466 dataset from the Gene Expression Omnibus, cross-referenced with the ferroptosis-related gene database FerrDB (version 2). A protein-protein interaction (PPI) network was constructed, identifying HSPA5 as a core hub gene. To validate its role in vivo, acute colitis was induced in C57BL/6 mice using DSS, followed by treatment with the ferroptosis inhibitor Ferrostatin-1 (Fer-1). Lipid peroxidation and ferroptosis levels were assessed by measuring malondialdehyde (MDA) and iron content in colon tissues. The expression of ferroptosis-related proteins, including prostaglandin-endoperoxide synthase 2 (PTGS2), glutathione peroxidase 4 (GPX4), ferritin light chain (FTL), activating transcription factor 4 (ATF4), and HSPA5, in addition to tight junction proteins ZO-1 and Occludin, were evaluated using immunohistochemistry and Western blotting. In vitro, an inflammatory model was established using lipopolysaccharide (LPS)-stimulated Caco-2 cells. Lentiviral knockdown of HSPA5 was performed to assess its regulatory effects on ferroptosis by assessing MDA levels, GPX4 activity, and the expression of related proteins. Statistical analyses were conducted with SPSS (version 29.1), with t-tests or one-way ANOVA for normally distributed data and the Mann-Whitney U test for ordinal data. Statistical significance was set at P<0.05. Results:Based on the PPI analysis and previous research, HSPA5 emerged as a key gene linking UC and ferroptosis. In DSS-treated mice, colonic injury was accompanied by elevated MDA levels ( t=5.72, P<0.001) and iron accumulation ( t=6.32, P<0.001). DSS also increased the expression of PTGS2 and proteins in the ATF4-HSPA5 pathway, while reducing the levels of GPX4, FTL, ZO-1, and Occludin. These findings could be partially reversed by Fer-1 (MDA: t=2.92, P<0.05; iron: t=5.84, P<0.001). In Caco-2 cells, LPS treatment elevated the expression of PTGS2, ATF4, and HSPA5, and elevated the MDA content ( t=9.63, P<0.001), while reducing the expression of FTL, GPX4, ZO-1, and Occludin, as well as GPX4 enzyme activity ( t=-11.20, P<0.001). Knockdown of HSPA5 further exacerbated these changes, significantly increasing MDA levels ( t=4.15, P<0.01), decreasing GPX4 activity ( t=-9.81, P<0.001), and altering ferroptosis-related protein expression. Conclusion:HSPA5 appears to protect against intestinal damage in UC by enhancing GPX4 expression and activity, thereby reducing ferroptosis and preserving epithelial barrier integrity through the maintenance of tight junction proteins.

Background/Aims: Obesity is associated with several gastrointestinal (GI) disorders and has been identified as a potential risk factor for various GI symptoms. Bowel frequency is an important indicator of bowel function. However, the causal link between obesity and gastrointestinal motility remains uncertain. This study aims to determine the causal effect of overall and central obesity on stool frequency. Methods: Four obesity-related anthropometric indicators–body mass index, body fat percentage, waist circumference (WC), and waist-tohip ratio (WHR)–were investigated. Individual-level baseline information from the UK Biobank was used to explore observational associations between obesity and stool frequency. Additionally, summary-level data from published genome-wide association studies were subjected to two-sample Mendelian randomization (MR) analyses to examine causal associations. Results: For all 4 indicators of obesity, higher levels of obesity were associated with more frequent bowel movements after adjusting for demographic characteristics, lifestyle, and dietary factors. After rigorous screening, 482 body mass index single nucleotide polymorphisms (SNPs), 7 body fat percentage SNPs, 48 WC SNPs, and 287 WHR SNPs were identified as instrument variables for MR analysis. The MR results were generally consistent with observational findings, proving that the associations observed in the overall obesity indicators were causal. For central obesity, the association between WHR and stool frequency remained consistent in both analysis phases, whereas WC showed a multidirectional association. Conclusions Obesity-related anthropometric indicators were causally associated with increased stool frequency in the overall and central obesity groups. Weight loss could be a potential approach to improve gastrointestinal regularity in individuals with obesity.

Objective To observe the efficacy of Venovo venous stent for treating post-thrombotic syndrome(PTS)after lower extremity deep venous thrombosis(DVT).Methods A total of 61 patients with PTS after lower extremioty DVT who underwent iliac vein stent implantation were retrospectively enrolled,including 33 cases underwent Venovo stent(Venovo stent group)and 28 cases underwent conventional stent implantation(conventional stent group).The technical success rates and perioperative complications,Villalta score and venous clinical severity score(VCSS)before and 6 and 12 months after treatment,as well as the primary stent patency were compared within and between groups.Results The technical success rate was 100%in both groups,and no significant difference of the incidence of perioperative complications was found between groups(P=0.187).There was no significant difference of Villalta score nor VCSS between groups before treatment(both P＞0.05),while significant decrease of Villalta score was noticed before and 6 or 12 months after treatment within both groups(all P＜0.05).No significant difference of Villalta score nor VCSS was found 6 months after treatment between groups(both P＞0.05),while significant difference of Villalta score and VCSS were observed in Venovo stent group compared with those in conventional stent group 12 months after treatment(both P＜0.05).No significant difference of primary stent patency rate was found between groups 6 and 12 months after treatment(both P＞0.05).Conclusion Venovo venous stent could be used to effectively treat PTS after lower extremity DVT.

Through data collection and collation combined with bibliometrics， this study conducted a series of textual research on Yanghetang， such as the name and origin， the evolution of prescription composition and modern clinical application. Yanghetang was first recorded in Bencao Yidu of WANG Ang in the Qing dynasty. In addition to Yanghetang， there were 3 bynames of Jiawei Yanghetang， Quanshengji Yanghetang and Zhenjun Yanghetang. Regarding the composition of the formula， a total of 4 versions of Yanghetang were collected. The first version is the 5 medicines version of Cervi Cornus Colla， Rehmanniae Radix Praeparata， Cinnamomi Cortex， Zingiberis Rhizoma and Ephedrae Herba in Bencao Yidu. The second version is the 7 medicines version of Waike Zhengzhi Quanshengji， changing Zingiberis Rhizoma to Zingiberis Rhizoma Praeparatum Carbonisata（ZRPC） and adding Sinapis Semen and Glycyrrhizae Radix et Rhizoma（GRR） on the basis of Bencao Yidu， and most of the Yanghetang is of this version. The third version is the 6 medicines version of Wushi Yifang Huibian， that is， on the basis of Bencao Yidu， Zingiberis Rhizoma is changed into ZRPC， and Sinapis Semen is added. The fourth version is the 6 medicines version in Yifang Jiedu， that is， on the basis of Bencao Yidu， Zingiberis Rhizoma is changed into Zingiberis Rhizoma Praeparatum， and GRR Praeparata cum Melle is added. Regarding the dose of Yanghetang， the doses of the medicines in Waike Zhengzhi Quanshengji was converted into the modern doses as follows：37.3 g of Rehmanniae Radix Praeparata， 1.87 g of Ephedrae Herba， 11.19 g of Cervi Cornus Colla， 7.46 g of Sinapis Semen， 3.73 g of Cinnamomi Cortex， 3.73 g of GRR， and 1.87 g of ZRPC. The origins of the above medicines are consistent with the 2020 edition of Chinese Pharmacopoeia. The processing specification of Rehmanniae Radix Praeparata is steaming method， ZRPC is ginger charcoal， Sinapis Semen is the fried products， and the rest of the medicines are raw products. The decoction method was verified by the decoction method in Chonglou Yuyao， which is similar in the time， and it is recommended that the above medicines should be added with 600 mL of water， decocted to 100 mL， and taken warmly 30 min after meal. For each dose， it is recommended to use 1-3 doses per day according to the doctor's advice in combination with clinical practice. The diseases involved in the ancient applications involved 42 diseases in 11 departments， including orthopedics， dermatology and gynecology， which were dominated by Yin-cold syndrome. However， the diseases involved in modern research also include 148 related diseases in 10 departments， such as orthopedics， obstetrics and gynecology， which is consistent with the ancient books. In recent years， the research hotspots of Yanghetang have focused on more than 10 fields， including osteoblasts， malignant tumors， wound healing， traditional Chinese medicine fumigation and so on， which are widely used. It is suitable for comprehensive research and development because of its rational formula composition， clear origin， processing and decoction method， and wide clinical application.