1.Investigation on the current status of pharmaceutical care in medical institutions in China
Tingting ZHENG ; Yuqing ZHANG ; Sitong LIU ; Wei ZHANG ; Jin LU ; Qunhong SHEN ; Jiancun ZHEN
China Pharmacy 2025;36(9):1117-1122
OBJECTIVE To investigate the current status of pharmaceutical care in medical institutions in China, and provide experience and suggestions for better development of pharmaceutical care. METHODS Questionnaire survey was used to investigate the development of pharmaceutical care in medical institutions in 31 provinces (autonomous regions and municipalities directly) in March 2023, and descriptive analysis and binary logistic regression analysis on the influencing factors of pharmaceutical care were conducted. RESULTS A total of 1 368 questionnaires were sent out, and 1 304 valid questionnaires were collected with the effective recovery rate of 95.32%. Pharmaceutical care was carried out in 671 medical institutions (51.46%), and the rates of pharmaceutical care in tertiary, secondary, primary and other medical institutions were 74.79%, 27.97% and 7.35%, respectively. The average number of patients receiving pharmaceutical care was 2 638.96 per year, and there were 8.33 pharmacists in each medical institution to carry out pharmaceutical care, among which 93.68% were clinical pharmacists. The main departments covered by pharmaceutical care services included respiratory and critical care medicine, cardiology, intensive care unit, endocrinology, oncology, gastroenterology, obstetrics and gynecology and other departments. There were only 48 medical institutions (7.15%) with additional compensation for pharmaceutical care services. The main experiences of developing pharmaceutical care were to pay attention to talent cultivation and discipline construction, but the main difficulties were serious shortage of staff and qualified talents, low compensation level and low enthusiasm. Grade of medical institutions, the number of pharmacists engaged in clinical pharmacy, the number of qualified clinical pharmacists and the degree of information in the pharmacy department were the main influencing factors for carrying out pharmaceutical care (P<0.05). CONCLUSIONS In recent years, pharmaceutical care in Chinese medical institutions has made certain progress, while that of primary medical institutions, secondary medical institutions and other medical institutions should be improved. In the future, it is still necessary to further enhance the implementation of pharmaceutical care, promote personnel training, and attach importance to demonstrating the value of pharmaceutical care, thereby promoting the sustainable and high- quality development of pharmaceutical care.
2.Effect of Shenkang Injection on Podocyte Apoptosis and GRP78/CHOP Signaling Pathway in db/db Mice with Diabetic Kidney Disease Based on Endoplasmic Reticulum Stress
Yanmo CAI ; Sitong WANG ; Xin ZHOU ; Ge JIN ; Kaidong ZHOU ; Yunhua LIU ; Fengfeng ZHANG ; Xinxue ZHANG ; Zongjiang ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):81-90
ObjectiveTo investigate the mechanism of Shenkang injection in delaying diabetic kidney disease by regulating endoplasmic reticulum stress and attenuating podocyte apoptosis through the Glucose regulated protein 78 ( GRP78 ) / transcription factor C / EBP homologous protein ( CHOP ) signaling pathway (GRP78/CHOP) signaling pathway. MethodsFor the animal experiment, 10 12-week-old db/m mice were selected as a normal group, and 30 12-week-old db/db mice were randomly divided into a model group, a Shenkang injection group (15.6 mL·kg-1), and a dapagliflozin group (1.6 mg·kg-1). To observe the general condition of mice, fasting blood glucose, urinary albumin/urine creatinine (ACR), and 24 h urine protein quantification were detected in each group before drug administration. After 12 weeks of drug treatment, mice were tested for fasting blood glucose, total cholesterol (TC), triglyceride (TG), low-density cholesterol (LDL), ACR, 24 h urine protein quantification, blood creatinine (SCr), and blood urea (UREA). Hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and transmission electron microscopy were used to observe the pathologic morphology in renal tissue. Immunohistochemistry was used to detect the expressions of nephroprotective marker protein (Nephrin), glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in renal tissue. Western blot was used to detect the expressions of GRP78, CHOP, Bcl-2, Bax, and Nephrin proteins, and Real-time polymerase chain reaction (Real-time PCR) was employed to detect the expressions of Nephrin, GRP78, CHOP, Bcl-2, and Bax mRNAs in renal tissue. ResultsBefore drug administration, compared with those in the normal group, the body mass of db/db mice was significantly increased, and blood glucose, 24 h urine protein quantification, and ACR were significantly elevated in the Shenkang injection group and Dapagliflozin group (P<0.01). After 12 weeks of administration, compared with those in the model group, the general state of mice in the Shenkang injection group was significantly improved, and the body mass was decreased. The blood glucose was significantly reduced (P<0.01), and blood lipids TC, TG, and LDL were significantly decreased (P<0.05, P<0.01). The 24 h urine protein quantification and ACR were significantly decreased (P<0.05), and SCr and UREA were significantly reduced (P<0.01). Compared with those of the model group, the pathologic results of the Shenkang injection group showed that proliferation of mesangial cells, reduction of inflammatory cell infiltration, and alleviation of renal tubular vacuolization and podocyte damage were observed in renal tissue of mice. Electron microscopy showed that fusion of the pedicle protruding and thickening of the basement membrane were reduced. Immunohistochemistry results showed that the expressions of GRP78, CHOP, and Bax proteins were significantly reduced (P<0.01), and the expressions of Nephrin and Bcl-2 proteins were significantly increased (P<0.01) in renal tissue of the Shenkang injection group. Western blot results showed that the expressions of Nephrin and Bcl-2 in the Shenkang injection group were significantly increased (P<0.05, P<0.01), and the expressions of GRP78, CHOP, and Bax proteins were significantly decreased (P<0.05, P<0.01). Real-time PCR results showed that the expressions of GRP78, CHOP, and Bax mRNAs were down regulated in the Shenkang injection group (P<0.01), and the expressions of Nephrin and Bcl-2 mRNAs were up regulated (P<0.01). ConclusionShenkang injection inhibits endoplasmic reticulum stress response and podocyte apoptosis by regulating the GRP78/CHOP signaling pathway, which in turn ensures the integrity of glomerular filtration barrier, reduces the occurrence of proteinuria, improves renal function, and thus delays the progression of diabetic kidney disease.
3.Effect of Shenkang Injection on Podocyte Apoptosis and GRP78/CHOP Signaling Pathway in db/db Mice with Diabetic Kidney Disease Based on Endoplasmic Reticulum Stress
Yanmo CAI ; Sitong WANG ; Xin ZHOU ; Ge JIN ; Kaidong ZHOU ; Yunhua LIU ; Fengfeng ZHANG ; Xinxue ZHANG ; Zongjiang ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):81-90
ObjectiveTo investigate the mechanism of Shenkang injection in delaying diabetic kidney disease by regulating endoplasmic reticulum stress and attenuating podocyte apoptosis through the Glucose regulated protein 78 ( GRP78 ) / transcription factor C / EBP homologous protein ( CHOP ) signaling pathway (GRP78/CHOP) signaling pathway. MethodsFor the animal experiment, 10 12-week-old db/m mice were selected as a normal group, and 30 12-week-old db/db mice were randomly divided into a model group, a Shenkang injection group (15.6 mL·kg-1), and a dapagliflozin group (1.6 mg·kg-1). To observe the general condition of mice, fasting blood glucose, urinary albumin/urine creatinine (ACR), and 24 h urine protein quantification were detected in each group before drug administration. After 12 weeks of drug treatment, mice were tested for fasting blood glucose, total cholesterol (TC), triglyceride (TG), low-density cholesterol (LDL), ACR, 24 h urine protein quantification, blood creatinine (SCr), and blood urea (UREA). Hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and transmission electron microscopy were used to observe the pathologic morphology in renal tissue. Immunohistochemistry was used to detect the expressions of nephroprotective marker protein (Nephrin), glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in renal tissue. Western blot was used to detect the expressions of GRP78, CHOP, Bcl-2, Bax, and Nephrin proteins, and Real-time polymerase chain reaction (Real-time PCR) was employed to detect the expressions of Nephrin, GRP78, CHOP, Bcl-2, and Bax mRNAs in renal tissue. ResultsBefore drug administration, compared with those in the normal group, the body mass of db/db mice was significantly increased, and blood glucose, 24 h urine protein quantification, and ACR were significantly elevated in the Shenkang injection group and Dapagliflozin group (P<0.01). After 12 weeks of administration, compared with those in the model group, the general state of mice in the Shenkang injection group was significantly improved, and the body mass was decreased. The blood glucose was significantly reduced (P<0.01), and blood lipids TC, TG, and LDL were significantly decreased (P<0.05, P<0.01). The 24 h urine protein quantification and ACR were significantly decreased (P<0.05), and SCr and UREA were significantly reduced (P<0.01). Compared with those of the model group, the pathologic results of the Shenkang injection group showed that proliferation of mesangial cells, reduction of inflammatory cell infiltration, and alleviation of renal tubular vacuolization and podocyte damage were observed in renal tissue of mice. Electron microscopy showed that fusion of the pedicle protruding and thickening of the basement membrane were reduced. Immunohistochemistry results showed that the expressions of GRP78, CHOP, and Bax proteins were significantly reduced (P<0.01), and the expressions of Nephrin and Bcl-2 proteins were significantly increased (P<0.01) in renal tissue of the Shenkang injection group. Western blot results showed that the expressions of Nephrin and Bcl-2 in the Shenkang injection group were significantly increased (P<0.05, P<0.01), and the expressions of GRP78, CHOP, and Bax proteins were significantly decreased (P<0.05, P<0.01). Real-time PCR results showed that the expressions of GRP78, CHOP, and Bax mRNAs were down regulated in the Shenkang injection group (P<0.01), and the expressions of Nephrin and Bcl-2 mRNAs were up regulated (P<0.01). ConclusionShenkang injection inhibits endoplasmic reticulum stress response and podocyte apoptosis by regulating the GRP78/CHOP signaling pathway, which in turn ensures the integrity of glomerular filtration barrier, reduces the occurrence of proteinuria, improves renal function, and thus delays the progression of diabetic kidney disease.
4.Yishen Huashi Granules Protect Kidneys of db/db Mice via p38 MAPK Signaling Pathway
Kaidong ZHOU ; Sitong WANG ; Ge JIN ; Yanmo CAI ; Xin ZHOU ; Yunhua LIU ; Xinxue ZHANG ; Min ZHANG ; Zongjiang ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):58-68
ObjectiveTo explore the mechanism of Yishen Huashi granules in alleviating renal tubular epithelial cell injury and relieving diabetic kidney disease by regulating the mitogen-activated protein kinase (MAPK) signaling pathway. MethodsThe db/db mice of 12 weeks old were randomly assigned into model , dapagliflozin (1.6 mg·kg-1), and Yishen Huashi granules (4.7 g·kg-1), and db/m mice were used as the control group. The general conditions of mice were observed, and fasting blood glucose and 24-h urinary protein and albumin-to-creatinine ratio (ACR) were measured at weeks 0 and 12 of administration. After 12 weeks of treatment, the levels of serum creatinine (SCr), blood urea (UREA), triglycerides (TG), total cholesterol (TC), and low density lipoprotein (LDL) were measured. The pathological changes in the renal tissue were observed by hematoxylin-eosin (HE) staining, Periodic acid-Schiff (PAS) staining, Mallory staining, and transmission electron microscopy. Real-time PCR was employed to determine the mRNA levels of monocyte chemotactic protein-1 (MCP-1) and CC chemokine receptor-2 (CCR2) in the renal tissue of mice. The immunohistochemical assay was employed to examine the expression of p38, phospho-p38 (p-p38), MCP-1, and CCR2 in the renal tissue of mice. Western blotting was employed to measure the protein levels of p-p38, p38, MCP-1, and CCR2 in the renal tissue of mice.HK-2 cells cultured in vitro were grouped as follows: negative control, high glucose(30 mmol·L-1), Yishen Huashi granule-containing serum, and SB203580. After 48 h of cell culture in each group, RNA were extracted and the levels of MCP-1, and CCR2 mRNA were determined by Real-time PCR,proteins were extracted and the levels of p38, p-p38, MCP-1, and CCR2 were determined by Western blot. ResultsThe in vivo experiments showed that before treatment, other groups had higher body weight, blood glucose level, 24 h urinary protein, and ACR than the control group (P<0.05,P<0.01). After 12 weeks of treatment, compared with the model group, the Yishen Huashi granules group showed improved general conditions, a decreasing trend in body weight, lowered levels of blood glucose, 24-h urinary protein, and ACR (P<0.01), reduced SCr and UREA (P<0.01), and declined levels of TC, TG, and LDL (P<0.05,P<0.01). Compared with the model group, the Yishen Huashi granules group showed alleviated damage and interstitial fibrosis in the renal tissue as well as reductions in glomerular foot process fusion and basement membrane thickening. Moreover, the Yishen Huashi granules group showed down-regulated mRNA levels of MCP-1 and CCR2 (P<0.01), reduced positive expression of p-p38, MCP-1, and CCR2 (P<0.01), and down-regulated protein levels of p-p38/p38, MCP-1, and CCR2 (P<0.05) in the renal tissue. The cell experiment showed that compared with the high glucose group, the Yishen Huashi granule-containing serum group showcased down-regulated mRNA levels of MCP-1 and CCR2 (P<0.01) and down-regulated protein levels of p-p38/p38, MCP-1, and CCR2(P<0.05,P<0.01). ConclusionYishen Huashi granules can regulate glucose-lipid metabolism, reduce 24 h urinary protein and ACR, improve the renal function, alleviate the renal tubule injury caused by high glucose, and protect renal tubule epithelial cells in db/db mice by reducing MCP-1/CCR2 activation via the p38 MAPK signaling pathway.
5.In Vitro and in vivo Component Identification of Danshenyin Based on UPLC-Q-TOF-MS/MS
Sitong ZHANG ; Xianrun HU ; Wenkang LIU ; Jinchun LEI ; Xuemei CHENG ; Xiaojun WU ; Wansheng CHEN ; Manlin LI ; Changhong WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):175-183
ObjectiveTo elucidate the chemical composition of Danshenyin and its blood components in rats after oral administration. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) coupled with PeakView 1.2 software was used to systematically characterize and identify the components of Danshenyin aqueous extract and its migratory components in rat blood after oral administration based on the retention time, quasi-molecular ion peaks, secondary fragmentation ions, and literature reports, and a preliminary compounds identification of Salviae Miltiorrhizae Radix et Rhizoma aqueous extract, the co-decoction of Santali Albi Lignum and Amomi Fructus was carried out to attribute the chemical constituents of the aqueous extract of Danshenyin. ResultsA total of 73 compounds, including 21 phenolic acids, 23 diterpenes, 6 flavonoids, 7 organic acids, 3 volatile oils and 13 others, were identified from the aqueous extract of Danshenyin. And 36 prototypes and 15 metabolites were identified in rat plasma, the major metabolic pathways included reduction, hydration, hydroxylation, demethylation, methylation, sulfation and others, these metabolites were mainly derived from tanshinones and salvianolic acids. ConclusionThe main blood components of the aqueous extract of Danshenyin are salvianolic acids and tanshinones, which may be the material basis of the efficacy. This study can provide reference for pharmacological research, quality control, and clinical application of Danshenyin.
6.Rationality evaluation of alteplase in the treatment of acute ischemic stroke based on weighted TOPSIS method
Sitong GUO ; Huiya CAI ; Henghai SU ; Jinhua ZHANG
Chinese Journal of Pharmacoepidemiology 2024;33(6):642-651
Objective To establish a drug use evaluation(DUE)criteria for alteplase in the treatment of acute ischemic stroke(AIS),and to evaluate the use of the drug by weighted TOPSIS method,to provide a reference for rational use of alteplase.Methods Based on the drug package insert,relevant guidelines,the DUE criteria for alteplase in the treatment of AIS were developed combined with expert consultation.The weighted TOPSIS method was used to evaluate the rationality of alteplase use in inpatients with AIS in the People's Hospital of Guangxi Zhuang Autonomous Region from January 2020 to June 2022,based on the attribute hierarchy model.Results A total of 126 medical records were included.Among them,80 cases(63.49%)exhibited a high degree of adherence(C,>0.8)between the prescribed drug regimens and the optimal recommendations,which was considered reasonable.Additionally,40 cases(31.75%)fell within the range of 0.6 ≤ Ci ≤ 0.8,indicating a basic reasonable adherence,and 6 cases(4.76%)had a C,<0.6,suggesting an unreasonable level of adherence.The irrational use of the drug mainly involved contraindications(32.54%),dosage(7.14%),and drug conversion(7.14%),among other aspects.Conclusion The weighted TOPSIS method is used to evaluate the rationality of alteplase in the treatment of acute ischemic stroke(AIS),and the results are intuitive and comprehensive.There are still problems in the use of alteplase in this hospital,and it is necessary to strengthen intervention to promote rational clinical use of alteplase in terms of contraindication of medication and dosage,etc.
7.Challenges and considerations in implementing enhanced recovery after surgery nursing for patients with hip fractures
Sitong YAN ; Ziruo ZHANG ; Peipei LI ; Cuicui LI ; Jing HU ; Wei HUANG
Chinese Journal of Modern Nursing 2024;30(6):701-706
This paper reviews the current status, problems, challenges, and considerations of enhanced recovery after surgery (ERAS) nursing for hip fracture patients in China, and systematically elaborates on the ERAS nursing programs, nursing pathways, and quality evaluation standards for hip fracture patients in China. In response to the challenges of differentiated starting, difficult clinical practice, and incomplete quality evaluation system in implementing ERAS nursing for hip fracture patients in China, suggestions are proposed to focus on national policies, standardize basic service content, optimize perioperative treatment and nursing processes for elderly hip fracture patients, strengthen the construction of ERAS nursing teams, and implement full cycle process management.
8.Predictive effect of age-adjusted Charlson comorbidity index on the risk of falls in elderly patients with femoral neck fractures
Ziruo ZHANG ; Jing HU ; Sitong YAN ; Peipei LI ; Hong ZHI ; Yuanyuan FENG ; Zhouqi JI
Chinese Journal of Modern Nursing 2024;30(11):1477-1482
Objective:To analyze the predictive value of age-adjusted Charlson comorbidity index (ACCI) on the risk of falls in elderly patients with femoral neck fractures.Methods:This study was a retrospective cohort study. From June 2021 to June 2022, cluster sampling was used to select 1 050 patients with femoral neck fractures at the Honghui Hospital affiliated with Xi'an Jiaotong University as the study subject. This study calculated the total ACCI score based on patient comorbidities, and divided patients into a low-risk fall group ( n=282) and a high-risk fall group ( n=768) based on whether the fall risk factor assessment score was ≥4.This study compared the differences in age, gender, American Society of Anesthesiologists (ASA) grading, ACCI score, white blood cell count, red blood cell count, platelet count, lymphocyte count, serum albumin, hemoglobin, creatinine, and urea nitrogen between the two groups. Independent variables with P<0.05 were included in binary Logistic regression to analyze the factors affecting the risk of falls in patients, and a receiver operating characteristic (ROC) curve was plotted. Results:There were statistically significant differences in age, ASA grading, red blood cell count, lymphocyte count, ACCI score, serum albumin, hemoglobin, creatinine, and urea nitrogen between the two groups of patients ( P<0.05). Logistic regression analysis found that age, ASA score, and ACCI score were independent risk factors for fall risk ( P<0.05), while serum albumin was an independent protective factor for fall risk ( P<0.05). The area under the ROC curve of ACCI for predicting fall risk was 0.892, and a score of 4 in ACCI was the cutoff value for predicting fall risk. Conclusions:ACCI can serve as an auxiliary tool for evaluating and predicting the risk of falls in elderly patients with femoral neck fractures, and can provide reference for clinical screening of high-risk individuals for falls.
9.Staphylococcus epidermidis phylotypes in hair follicles in skin lesions of patients with moderate acne vulgaris: a preliminary study
Jiaqi LI ; Mengchen LIANG ; Xinyi WU ; Qiujing ZHANG ; Sitong LI ; Xiaohui MO ; Qiang JU
Chinese Journal of Dermatology 2024;57(4):295-301
Objective:To compare the phylotypes of Staphylococcus epidermidis (SE) in skin lesions of acne vulgaris patients versus hair follicles of healthy people, and to analyze their roles in the pathogenesis of acne vulgaris. Methods:A cross-sectional study was conducted from August 2022 to August 2023. Patients with moderate acne vulgaris, as well as healthy volunteers, were enrolled from the Department of Dermatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University. SE strains were isolated from the pustules of acne vulgaris patients and hair follicles of healthy volunteers. Housekeeping genes were amplified by PCR. Sequencing and multilocus sequence typing were performed to compare the phylotypes and genetic relationships of strains from different sources.Results:The acne group consisted of 28 patients (10 males and 18 females) with the age being 22.6 ± 2.6 years, while the healthy group consisted of 19 volunteers (7 males and 12 females) with the age being 22.4 ± 0.96 years. There were no significant differences in age or gender ratio between the two groups (both P > 0.05). The positive rates of SE in the samples of the acne group and the healthy group were 60.71% (17/28) and 73.68% (14/19), respectively, with no significant difference between the two groups ( P = 0.53). The 144 SE strains from the healthy group could be divided into 10 sequence types (STs), and the most common ST was ST35 (8 cases), followed by ST73 (4 cases), ST193 (2 cases), ST59 (2 cases) and ST540 (2 cases) ; 190 SE strains from the acne group could be divided into 16 STs, and the most common STs were ST59 (6 cases) and ST73 (6 cases), followed by ST802 (3 cases), ST130 (3 cases) and ST35 (2 cases). The positive rate of ST35 was significantly lower in the acne group than in the healthy group ( P = 0.018), while there were no significant differences in the positive rates of other STs between the two groups (all P > 0.05). The evolutionary tree analysis showed that the SE strains were mainly distributed in 3 branches. Most of the SE strains from the healthy group belonged to clade A. The proportion of SE strains in clade A ( M[ Q]) was significantly lower in the acne group (25% [85%]) than in the healthy group (100% [33.33%], P = 0.025), while the proportion of SE strains in clade B was significantly higher in the acne group (14.29% [89.17%]) than in the healthy group (0[0], U = 62, P = 0.010), and there was no significant difference in the proportion of SE strains in clade D between the acne group (0 [57.14%]) and healthy group (0[4.17%], P = 0.420) . Conclusion:The phylotypes of SE strains differed between acne vulgaris patients and healthy controls, possibly associated with the occurrence and development of acne vulgaris.
10.Exploring the causality between intestinal flora and hyperplastic scars of human based on two-sample Mendelian randomization analysis
Wentao CHEN ; Xiaoxiang WANG ; Wenlian ZHENG ; Weiqiang ZHANG ; Lujia MAO ; Jianan ZHUO ; Sitong ZHOU ; Ronghua YANG
Chinese Journal of Burns 2024;40(4):333-341
Objective:To investigate the causality between intestinal flora and hypertrophic scars (HS) of human.Methods:This study was a study based on two-sample Mendelian randomization (TSMR) analysis. The data on intestinal flora ( n=18 473) and HS ( n=208 248) of human were obtained from the genome-wide association study database. Genetically variable genes at five levels (phylum, class, order, family, and genus) of known intestinal flora, i.e., single nucleotide polymorphisms (SNPs), were extracted as instrumental variables for linkage disequilibrium (LD) analysis. Human genotype-phenotype association analysis was performed using PhenoScanner V2 database to exclude SNPs unrelated to HS in intestinal flora and analyze whether the selected SNPs were weak instrumental variables. The causal relationship between intestinal flora SNPs and HS was analyzed through four methods of TSMR analysis, namely inverse variance weighted (IVW), MR-Egger regression, weighted median, and weighted mode. Scatter plots of significant results from the four aforementioned analysis methods were plotted to analyze the correlation between intestinal flora SNPs and HS. Both IVW test and MR-Egger regression test were used to assess the heterogeneity of intestinal flora SNPs, MR-Egger regression test and MR-PRESSO outlier test were used to assess the horizontal multiplicity of intestinal flora SNPs, and leave-one-out sensitivity analysis was used to determine whether HS was caused by a single SNP in the intestinal flora. Reverse TSMR analyses were performed for HS SNPs and genus Intestinimonas or genus Ruminococcus2, respectively, to detect whether there was reverse causality between them. Results:A total of 196 known intestinal flora, belonging to 9 phyla, 16 classes, 20 orders, 32 families, and 119 genera, were obtained, and multiple SNPs were obtained from each flora as instrumental variables. LD analysis showed that the SNPs of the intestinal flora were consistent with the hypothesis that genetic variation was strongly associated with exposure factors, except for rs1000888, rs12566247, and rs994794. Human genotype-phenotype association analysis showed that none of the selected SNPs after LD analysis was excluded and there were no weak instrumental variables. IVW, MR-Egger regression, weighted median, and weighted mode of TSMR analysis showed that both genus Intestinimonas and genus Ruminococcus2 were causally associated with HS. Among them, forest plots of IVW and MR-Egger regression analyses also showed that 16 SNPs (the same SNPs number of this genus below) of genus Intestinimonas and 15 SNPs (the same SNPs number of this genus below) of genus Ruminococcus2 were protective factors for HS. Further, IVW analysis showed that genus Intestinimonas SNPs (with odds ratio of 0.62, 95% confidence interval of 0.41-0.93, P<0.05) and genus Ruminococcus2 SNPs (with odds ratio of 0.62, 95% confidence interval of 0.40-0.97, P<0.05) were negatively correlated with the risk of HS. Scatter plots showed that SNPs of genus Intestinimonas and genus Ruminococcus2 were protective factors of HS. Both IVW test and MR-Egger regression test showed that SNPs of genus Intestinimonas (with Q values of 5.73 and 5.76, respectively, P>0.05) and genus Ruminococcus2 (with Q values of 13.67 and 15.61, respectively, P>0.05) were not heterogeneous. MR-Egger regression test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity (with intercepts of 0.01 and 0.06, respectively, P>0.05); MR-PRESSO outlier test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity ( P>0.05). Leave-one-out sensitivity analysis showed that no single intestinal flora SNP drove the occurrence of HS. Reverse TSMR analysis showed no reverse causality between HS SNPs and genus Intestinimonas or genus Ruminococcus2 (with odds ratios of 1.01 and 0.99, respectively, 95% confidence intervals of 0.97-1.06 and 0.96-1.04, respectively, P>0.05). Conclusions:There is a causal relationship between intestinal flora and HS of human, in which genus Intestinimonas and genus Ruminococcus2 have a certain effect on inhibiting HS.

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