ObjectiveTo observe the effects of Danggui Shaoyaosan on macrophage polarization and renal inflammation in db/db mice with diabetic kidney disease （DKD）， and to explore its renal protective effects and underlying mechanisms. MethodsEight db/m mice were assigned to the normal group， and forty db/db mice were randomly divided into a model group， low-， medium-， and high-dose Danggui Shaoyaosan groups （8.39， 16.77， 33.54 g·kg^-1）， and an irbesartan group （0.025 g·kg^-1）. All mice were administered treatment by gavage for 12 consecutive weeks. General conditions of the mice were observed during the intervention. At the end of the 12-week intervention， 24-h urine samples were collected using metabolic cages， after which the mice were anesthetized for sample collection. Blood was collected by enucleation and centrifuged to obtain serum for the determination of glycated serum protein （GSP）， serum creatinine （SCr）， blood urea nitrogen （BUN）， total cholesterol （TC）， and triglycerides （TG）. The urinary albumin-to-creatinine ratio （UACR） was measured. Renal pathological changes were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and monocyte chemoattractant protein-1 （MCP-1） levels. Immunofluorescence （IF） was performed to detect F4/80 expression in renal tissue， and immunohistochemistry （IHC） was used to assess CD206 expression. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA expression of TNF-α， IL-10， inducible nitric oxide synthase （iNOS）， and arginase-1 （Arg-1）. Western blot analysis was used to detect the protein expression of iNOS， Arg-1， CD86， and CD206 in renal tissue. ResultsCompared with the normal group， the model group showed increased levels of GSP， UACR， SCr， BUN， TC， and TG， elevated levels of the inflammatory factor TNF-α and the chemokine MCP-1， and decreased IL-10 levels （P<0.01）. Pathological examination revealed glomerular hypertrophy， mesangial cell proliferation with marked mesangial expansion， inflammatory cell infiltration， vacuolar degeneration of renal tubular epithelial cells， prominent glycogen deposition， and increased collagen fiber deposition. In addition， relative F4/80 fluorescence intensity was enhanced， CD206 expression in the glomeruli and renal interstitium was reduced， and TNF-α and iNOS mRNA expression was increased. IL-10 and Arg-1 mRNA expression was decreased， iNOS and CD86 protein expression was increased， and Arg-1 and CD206 protein expression was decreased （P<0.05， P<0.01）. Compared with the model group， the Danggui Shaoyaosan groups and the irbesartan group showed decreased levels of GSP， UACR， SCr， BUN， TC， and TG， reduced serum TNF-α and MCP-1 levels， and increased IL-10 levels. Renal pathological damage was improved to varying degrees. Relative F4/80 fluorescence intensity was reduced， CD206 expression in the glomeruli and renal interstitium was increased， and TNF-α and iNOS mRNA expression was decreased. IL-10 and Arg-1 mRNA expression was increased， iNOS and CD86 protein expression was reduced， and Arg-1 and CD206 protein expression was increased （P<0.05， P<0.01）. ConclusionDanggui Shaoyaosan can improve renal function and alleviate renal pathological damage in db/db mice. Its mechanism may be related to inhibiting M1 pro-inflammatory macrophage polarization， promoting M2 anti-inflammatory macrophage polarization， reducing inflammatory responses， delaying the progression of renal fibrosis， improving renal pathological injury， and thereby exerting renal protective effects.

ObjectiveTo investigate the potential mechanism of Danggui Shaoyaosan （DSS） in ameliorating renal injury in db/db mice. MethodsThirty 8-week-old specific pathogen-free （SPF）-grade male db/db mice and six db/m mice were acclimated for one week. Urinary microalbumin and blood glucose levels were measured weekly in both db/db and db/m mice. Successful modeling was determined by significantly higher microalbuminuria in db/db mice compared to db/m mice and a fasting blood glucose ≥16.7 mmol·L^-1. The 30 db/db mice were randomly divided into five groups： the model group， the irbesartan （IBN） group， and three DSS dose groups （low-， medium-， and high-dose DSS groups， administered at 16.77， 33.54， 67.08 g·kg^-1·d^-1， respectively）. Additionally， the six db/m mice served as the normal control group. The IBN group received irbesartan at 0.025 g·kg^-1·d^-1 by gavage， while the three DSS groups received DSS at 16.77， 33.54， and 67.08 g·kg^-1·d^-1 by gavage， respectively. The normal and model groups were administered with an equivalent volume of normal saline by gavage. All interventions lasted for 8 consecutive weeks. After intervention， serum creatinine （SCr）， blood urea nitrogen （BUN）， urinary total protein （UTP）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） were measured to evaluate the therapeutic efficacy of the treatments. Renal histopathological changes were observed with hematoxylin-eosin （HE） staining. Western blot was used to detect the protein expression of silencing information regulator 1 （SIRT1）， hypoxia-inducible factor-1α （HIF-1α）， very low-density lipoprotein receptor （VLDLr）， and cluster of differentiation 31 （CD31）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA levels of HIF-1α and VLDLr. Immunohistochemistry was used to observe the expression and distribution of HIF-1α and Caspase-3. ResultsCompared to the normal group， the model group showed significantly increased SCr， BUN， UTP， TG， and LDL-C. HE staining revealed glomerulosclerosis， mesangial matrix hyperplasia， capillary loop distortion and thickening， with extensive inflammatory cell infiltration. Protein expression of SIRT1 and CD31 significantly decreased （P<0.05）， while HIF-1α and VLDLr protein and mRNA levels increased （P<0.05）. Immunohistochemistry showed increased expression of HIF-1α and Caspase-3 （P<0.05）， indicating hypoxia and apoptosis in renal cells. In all treatment groups， SCr， BUN， TG， and LDL-C were significantly reduced compared to the model group （P<0.05）， and UTP was significantly improved in the medium-dose DSS group （P<0.05）. Renal tissue structure and morphology were improved， inflammatory cells were reduced， and no vascular hyaline degeneration was observed. SIRT1 and CD31 protein expression was elevated to varying degrees compared to the model group （P<0.05）， while HIF-1α and VLDLr protein and mRNA levels decreased （P<0.05）. Immunohistochemistry showed reduced expression of HIF-1α and Caspase-3 in all treatment groups （P<0.05）， with the most significant improvement observed in the IBN group and medium-dose DSS group （P<0.05）. ConclusionDSS can effectively ameliorate glomerulosclerosis and lipid deposition in db/db mice， and its mechanism may involve the SIRT1/HIF-1α/VLDLr signaling pathway.

ObjectiveTo investigate the effect of Danggui Shaoyaosan on the expression of Toll-like receptor 4/nuclear factor-kappa B p65/NOD-like receptor protein 3 （TLR4/NF-κB p65/NLRP3） signaling pathway in the renal tissues of db/db mice with spontaneous diabetes， and to explore the potential mechanism by which Danggui Shaoyaosan alleviates inflammation in diabetic kidney disease （DKD）. MethodsThirty db/db mice were divided into five groups： A model group， Danggui Shaoyaosan low- （16.77 g·kg^-1·d^-1）， medium- （33.54 g·kg^-1·d^-1）， and high-dose （67.08 g·kg^-1·d^-1） intervention groups， as well as an irbesartan group （0.025 g·kg^-1·d^-1） by the random number table method， with 6 mice in each group. Additionally， 6 db/m mice were assigned to the normal group. After 8 weeks of intervention， the following parameters were determined by corresponding methods： body weight， fasting blood glucose （FBG）， 24-hour urinary protein （24 h-UTP）， and serum creatinine （SCr） levels， renal histopathological analysis by hematoxylin-eosin （HE） staining， Masson staining， and periodic acid-Schiff （PAS） staining， the protein and mRNA expression levels of TLR4， NF-κB p65， NLRP3， tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-10 （IL-10）， and interleukin-18 （IL-18） by Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR）， as well as TLR4， NF-κB p65， and NLRP3 protein expression in renal tissues by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group exhibited increased body weight， FBG， 24 h-UTP， and SCr levels （P<0.05）； disordered renal structure， thickened basement membrane， and interstitial inflammatory cell infiltration， elevated TLR4， NF-κB p65， NLRP3， TNF-α， IL-1β， IL-6， and IL-18 expression； as well as decreased IL-10 expression （P<0.05）. Compared with the model group， these pathological changes and biochemical abnormalities were reversed in the medicine intervention groups to varying degrees （P<0.05）. ConclusionDanggui Shaoyaosan may delay DKD progression by alleviating renal inflammatory response and reducing urinary protein excretion via modulating the TLR4/NF-κB p65/NLRP3 signaling pathway.

ObjectiveTo investigate the therapeutic efficacy of Danggui Shaoyaosan （DSS） on renal injury in db/db mice and its impact on endoplasmic reticulum stress （ERS） in renal tissues. MethodsThirty 8-week-old male db/db mice and six db/m mice were acclimated for one week， after which urinary microalbumin and blood glucose levels were monitored to establish a diabetic kidney disease （DKD） model. The model mice were randomly divided into a model group， an irbesartan group， and three DSS treatment groups with different doses （16.77， 33.54， and 67.08 g·kg^-1·d^-1）. A normal group was set as control. Each group was intragastrically administered with the corresponding drugs or saline for 8 weeks. After the intervention， general conditions were observed. Serum cystatin C （Cys-C）， 24-hour urinary total protein （24 h-UTP）， 24-hour urinary microalbumin （24 h-UMA）， urinary creatinine （Ucr）， and urea nitrogen （UUN） were measured. Transmission electron microscopy （TEM） was used to observe glomerular basement membrane （GBM） and ultrastructural changes of the endoplasmic reticulum （ER） in glomerular endothelial cells. Western blot， real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and immunohistochemistry were used to analyze renal tissue structure and the expression of GRP78， CHOP， and related markers. ResultsCompared with the normal group， the mice in the model group showed curled posture， sluggish response， poor fur condition， increased levels of Cys-C， 24 h-UTP， 24 h-UMA， and UUN （P<0.05）， while Ucr decreased （P<0.05）. The GBM was significantly thickened， with podocyte and foot process fusion. The protein expressions of GRP78， CHOP， and ATF6 were significantly upregulated （P<0.05）， the mRNA levels of GRP78 and CHOP increased （P<0.05）， and immunohistochemistry showed an enhanced GRP78 signal （P<0.05）. After treatment， the mice exhibited improved behavior， normalized GBM and podocyte structure， improved ER morphology and markedly better biochemical indicators. Western blot， Real-time PCR， and immunohistochemistry indicated that the ERS-related markers were downregulated in the DSS treatment groups （P<0.05）， suggesting alleviated ERS and improved renal function. ConclusionDSS can effectively ameliorate renal pathological damage in db/db mice， possibly by regulating ERS in glomerular endothelial cells， although the underlying signaling mechanisms require further investigation.

Hepatocellular carcinoma （HCC）， the predominant subtype of primary liver cancer， ranks among the top in both incidence and mortality rates of malignant tumors in China. In its early stages， the disease may present with subtle or nonspecific symptoms， often leading to poor clinical prognosis and low patient survival rates， which makes it a significant public health concern. The pathogenesis is associated with multiple factors， including hepatitis virus infection， alcohol consumption， obesity， drug-induced liver injury， and immune disorders， which may interact synergistically to promote disease development. Currently， mainstream therapeutic approaches for HCC in modern medicine encompass surgical resection， liver transplantation， radiofrequency ablation， radiotherapy， and chemotherapy， but they all have certain limitations， such as large side effects and poor prognosis， imposing substantial psychological distress and financial strain on affected individuals. With a rich historical background in hepatic malignancy management， traditional Chinese medicine offers therapeutic benefits characterized by multi-targeted mechanisms， multi-level regulation， minimal adverse effects， and reduced likelihood of disease recurrence. It can not only enhance the curative effect， but also reduce the side effects of radiotherapy， chemotherapy， and surgery. Thus， it has attracted widespread attention. Extensive research has demonstrated that traditional Chinese medicine exhibits significant antitumor properties， along with notable anti-inflammatory and oxidative stress-reducing capabilities， and its mechanism may be related to the regulation of nuclear factor-kappa B （NF-κB） signaling pathway， which can affect multiple stages of hepatocarcinogenesis， such as cell proliferation， invasion， metastasis， and apoptosis. The mechanism of NF-κB signaling pathway in traditional Chinese medicine for HCC treatment has emerged as one of the pivotal research directions in current oncology studies. Based on the existing research foundation， a systematic literature review method was adopted to retrieve and analyze relevant Chinese and English literature in recent years. Integrating the molecular regulatory mechanisms of the NF-κB signaling pathway and its pivotal role in HCC pathogenesis and progression helped further explore the latest research advances in traditional Chinese medicine interventions targeting this pathway for HCC treatment. This approach may provide novel theoretical foundations and translational strategies for the prevention and management of HCC using traditional Chinese medicine.

ObjectiveTo investigate whether Danggui Shaoyaosan （DSS） inhibits oxidative stress and alleviates inflammation via the Ras homolog family member A （RhoA）/Rho-associated coiled-coil containing protein kinase 1 （ROCK）/nuclear factor kappa-B （NF-κB） signaling pathway， thereby delaying the progression of diabetic kidney disease （DKD） and exerting a nephroprotective effect. MethodsEight db/m mice were assigned to the normal group， and forty 8-week-old db/db mice were randomly divided into the model group， DSS low-dose group （8.39 g·kg^-1）， DSS medium-dose group （16.77 g·kg^-1）， DSS high-dose group （33.54 g·kg^-1）， and irbesartan group （0.025 g·kg^-1）， with eight mice in each group. All groups were administered the corresponding treatment by gavage once daily for 12 weeks. The normal and model groups received an equal volume of saline. During administration， changes in body weight， fasting blood glucose （FBG）， and 24 hour urinary protein （24 h UTP） were observed. After 12 consecutive weeks of administration， hematoxylin-eosin （HE） staining and Masson's trichrome staining were used to observe renal histopathological changes in each group. The levels of reactive oxygen species （ROS） in renal tissue were detected using the dihydroethidium （DHE） method. The expression levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in renal tissue were determined. Serum interleukin-1β （IL-1β） and interleukin-6 （IL-6） levels were measured using enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of RhoA， ROCK1， and NF-κB p65 in renal tissues were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. Protein expression levels of fibronectin （FN）， Collagen Ⅳ（Col Ⅳ）， transforming growth factor-β₁ （TGF-β₁）， RhoA， ROCK， and NF-κB p65 in renal tissues were determined by Western blot. ResultsCompared with the normal group， the model group showed significantly increased body weight， FBG， and 24 h UTP levels （P<0.01）， elevated serum IL-1β and IL-6 levels， enlarged glomerular volume， diffuse mesangial expansion， increased mesangial matrix， and marked collagen fiber proliferation in renal tissues. SOD activity was decreased， while MDA， ROS， RhoA， ROCK1， and NF-κB p65 mRNA expression levels were increased （P<0.01）， and the protein expression levels of FN， Col Ⅳ， TGF-β₁， RhoA， ROCK， and NF-κB p65 were also elevated （P<0.01）. Compared with the model group， the DSS low-， medium-， and high-dose groups and the irbesartan group showed reductions in body weight， FBG， and 24 h UTP， decreased serum IL-1β and IL-6 levels， varying degrees of improvement in renal histopathology， increased SOD activity， decreased MDA levels， reduced ROS expression， and significantly downregulated RhoA， ROCK1， and NF-κB p65 mRNA expression （P<0.05， P<0.01）， as well as reduced protein expression levels of FN， Col Ⅳ， TGF-β₁， RhoA， ROCK， and NF-κB p65 （P<0.05， P<0.01）. ConclusionDSS can alleviate oxidative stress and inflammation， reduce extracellular matrix deposition， and delay renal fibrosis progression in db/db mice. Its mechanism may be related to the inhibition of the RhoA/ROCK/NF-κB signaling pathway， thereby exerting a therapeutic effect on DKD.

OBJECTIVE: To explore the corrective strategies and effectiveness of osteotomy surgery for severe lower limb deformities in hypophosphatemic rickets. METHODS: A retrospective analysis was conducted on 29 patients with severe lower limb deformities of hypophosphatemic rickets who underwent surgical treatment between February 2012 and August 2024. There were 9 males and 20 females. The age ranged from 13 to 53 years, with an average of 24.6 years. All patients were deformities of both lower limbs, presenting as 24 cases of O-shaped legs, 2 cases of wind-blown deformities, and 3 cases of X-shaped legs. Based on the full-length films of both lower limbs in the standing position before operation, the osteotomy planes of the femur, tibia, and fibula were designed. Among them, if both the same-sided thigh and leg were deformed, staged surgeries of both lower limbs were selected. If only the thigh or leg were deformed, simultaneous surgeries of both lower limbs were selected. The femur deformity was corrected immediately after osteotomy at the deformed plane; the osteotomy fragment was temporarily controlled with an external fixator, which was removed after perform internal fixation with a steel plate. After fibular osteotomy, the Ilizarov frame or Taylor frame was installed on the tibia and fibula. The threaded rods were removed and then tibial osteotomy was performed on the deformed plane. Patients using the Taylor frame did not undergo deformity correction during operation. The external fixators were adjusted starting 7 days after operation to correct the varus, valgus, and rotational deformities of the lower limb. Patients using the Ilizarov frame corrected the rotational deformity of the tibia during operation. The external fixator was adjusted starting 7 days after operation to correct the varus and valgus deformities of the lower limb. During the treatment period, the patient could walk with partial weight-bearing on the operated limb with crutches. The external fixator was removed after the bone healed. Before operation and at last follow-up, the medial proximal tibial angle (MPTA), lateral distal tibial angle (LDTA), posterior proximal tibial angle (PPTA), anterior distal tibial angle (ADTA), anatomic lateral distal femoral angle (aLDFA), posterior distal femoral angle (PDFA), and mechanical axis deviation (MAD), lower limb rotation, limb length discrepancy (LLD) were measured. The self-made scoring criteria were adopted to evaluate the degree of lower limb deformity of the patients. RESULTS: All operations were successfully completed, and no complications such as nerve or vascular injury occurred. The adjustment time of the external fixator of the lower limb after operation was 28-46 days, with an average of 37.4 days. The wearing time of the external fixator ranged from 134 to 398 days, with an average of 181.5 days. Mild pin tract infections occurred in 2 limbs. The osteofascial compartment syndrome occurred in 1 limb after operation. No complications related to orthopedic adjustment of the external fixator occurred in other patients. All patients were followed up 6-56 months, with an average of 28.2 months. At last follow-up, full-length films of both lower limbs in the standing position showed that the coronal mechanical axes of the lower limbs of all patients returned to the normal. At last follow-up, MPTA, LDTA, PPTA, aLDFA, PDFA, MAD, lower limb rotation, LLD, and the score of lower limb deformity significantly improved when compared with those before operation ( P<0.05). There was no significant difference in ADTA between pre- and post-operation ( P>0.05). The degree of lower limb deformity were rated as moderate in 2 cases and poor in 27 cases before operation and as excellent in 7 cases, good in 18 cases, and moderate in 4 cases at last follow-up, with an excellent and good rate of 86.2%. CONCLUSION For severe lower limb deformities in hypophosphatemic rickets, immediate correction of deformities with femoral osteotomy and internal plate fixation, as well as gradually correction of deformities with tibiofibular osteotomy and circular external fixation (Ilizarov frame or Taylor frame), have satisfactory therapeutic effects.
Humans ; Male ; Osteotomy/instrumentation* ; Female ; Adult ; Retrospective Studies ; Tibia/abnormalities* ; Adolescent ; Femur/abnormalities* ; Middle Aged ; Fibula/surgery* ; Rickets, Hypophosphatemic/complications* ; Young Adult ; Treatment Outcome ; External Fixators ; Bone Plates ; Lower Extremity Deformities, Congenital/etiology*

Objective:To investigate the correlation between metabolic syndrome (MS), its different components and the risk of cholecystolithiasis and gallbladder polyp in Uygur population in rural areas of southern Xinjiang.Methods:This study was a prospective cohort study. A baseline survey was conducted in August 2016. A typical sampling method was used to select 10 476 Uygur people in rural areas of southern Xinjiang as the research objects. Baseline clinical data were collected, including demographic data such as age, gender, and education level, and laboratory examination indicators such as blood glucose and triglyceride levels. According to the MS diagnostic criteria of the relevant guidelines, 10 476 subjects were divided into the MS group (3 475 cases) and the non-MS group (7 001 cases). The incidence of cholecystolithiasis and gallbladder polyp was followed up in 2019, 2021 and 2023, respectively. Cox regression was used to analyze the correlation between MS, its different components and the risk of cholecystolithiasis and gallbladder polyp. Chi-square test and independent sample t test were used for statistical analysis. Results:The median follow-up time was 6.43 years in 10 476 subjects, and the overall cumulative incidence of cholecystolithiasis and gallbladder polyp was 5.43% (569/10 476). The cumulative incidence of cholecystolithiasis and gallbladder polyp in the MS group was 10.73% (373/ 3 475), which was significantly higher than that in the non-MS group (2.80% (196/7 001)); χ2= 284.62, P<0.001). The results of multivariate Cox regression analysis showed that, 41 to 59 years old ( HR=1.26, 95% confidence interval (95% CI): 1.03 to 1.54, P=0.025), ≥60 years old ( HR=1.88, 95% CI: 1.45 to 2.45, P<0.001), female ( HR=1.34, 95% CI: 1.13 to 1.60, P=0.001), MS ( HR=2.19, 95% CI: 1.59 to 3.01, P<0.001), hypertriglyceridemia ( HR=1.47, 95% CI: 1.18 to 1.83, P=0.001), hypertension ( HR=1.30, 95% CI: 1.04 to 1.62, P=0.023), and hyperglycemia ( HR=1.24, 95% CI: 1.01 to 1.52, P=0.041) were independent risk factors for cholecystolithiasis and gallbladder polyp. After the adjustment of age and gender, MS ( HR=3.39, 95% CI: 2.82 to 4.07, P<0.001), hypertriglyceridemia ( HR=2.37, 95% CI: 2.00 to 2.81, P<0.001), hypertension ( HR=2.00, 95% CI: 1.66 to 2.41, P<0.001), and hyperglycemia ( HR=1.86, 95% CI: 1.55 to 2.23, P<0.001) were still correlated with cholecystolithiasis and gallbladder polyp, and there was the srtongest correlation between MS and cholecystolithiasis and gallbladder polyp. The results of univariate Cox regression analysis showed that along with the increase of accumulated of MS components, the risk of cholecystolithiasis and gallbladder polyp significantly increased (1 to 5 components corresponding HR (95% CI) were 1.92 (1.13 to 3.24), 2.21 (1.32 to 3.69), 6.91 (4.22 to 11.30), 8.56 (5.15 to 14.22), and 10.73 (5.66 to 20.33); P=0.015, =0.002, <0.001, <0.001, and <0.001); after age and gender were adjusted, this trend still existed (1 to 5 components corresponding HR (95% CI) were 1.81(1.07 to 3.06), 1.95(1.16 to 3.27), 5.64(3.42 to 9.32), 6.69(3.97 to 11.25), and 7.76(4.04 to 14.91); P=0.028, =0.012, <0.001, <0.001, and <0.001). Conclusion:MS and its components can increase the risk of cholecystolithiasis and gallbladder polyp, and the risk of cholecystolithiasis and gallbladder polyp significantly increases along with the increase of accumulated of MS components.

Objective:To investigate the correlation between metabolic syndrome (MS), its different components and the risk of cholecystolithiasis and gallbladder polyp in Uygur population in rural areas of southern Xinjiang.Methods:This study was a prospective cohort study. A baseline survey was conducted in August 2016. A typical sampling method was used to select 10 476 Uygur people in rural areas of southern Xinjiang as the research objects. Baseline clinical data were collected, including demographic data such as age, gender, and education level, and laboratory examination indicators such as blood glucose and triglyceride levels. According to the MS diagnostic criteria of the relevant guidelines, 10 476 subjects were divided into the MS group (3 475 cases) and the non-MS group (7 001 cases). The incidence of cholecystolithiasis and gallbladder polyp was followed up in 2019, 2021 and 2023, respectively. Cox regression was used to analyze the correlation between MS, its different components and the risk of cholecystolithiasis and gallbladder polyp. Chi-square test and independent sample t test were used for statistical analysis. Results:The median follow-up time was 6.43 years in 10 476 subjects, and the overall cumulative incidence of cholecystolithiasis and gallbladder polyp was 5.43% (569/10 476). The cumulative incidence of cholecystolithiasis and gallbladder polyp in the MS group was 10.73% (373/ 3 475), which was significantly higher than that in the non-MS group (2.80% (196/7 001)); χ2= 284.62, P<0.001). The results of multivariate Cox regression analysis showed that, 41 to 59 years old ( HR=1.26, 95% confidence interval (95% CI): 1.03 to 1.54, P=0.025), ≥60 years old ( HR=1.88, 95% CI: 1.45 to 2.45, P<0.001), female ( HR=1.34, 95% CI: 1.13 to 1.60, P=0.001), MS ( HR=2.19, 95% CI: 1.59 to 3.01, P<0.001), hypertriglyceridemia ( HR=1.47, 95% CI: 1.18 to 1.83, P=0.001), hypertension ( HR=1.30, 95% CI: 1.04 to 1.62, P=0.023), and hyperglycemia ( HR=1.24, 95% CI: 1.01 to 1.52, P=0.041) were independent risk factors for cholecystolithiasis and gallbladder polyp. After the adjustment of age and gender, MS ( HR=3.39, 95% CI: 2.82 to 4.07, P<0.001), hypertriglyceridemia ( HR=2.37, 95% CI: 2.00 to 2.81, P<0.001), hypertension ( HR=2.00, 95% CI: 1.66 to 2.41, P<0.001), and hyperglycemia ( HR=1.86, 95% CI: 1.55 to 2.23, P<0.001) were still correlated with cholecystolithiasis and gallbladder polyp, and there was the srtongest correlation between MS and cholecystolithiasis and gallbladder polyp. The results of univariate Cox regression analysis showed that along with the increase of accumulated of MS components, the risk of cholecystolithiasis and gallbladder polyp significantly increased (1 to 5 components corresponding HR (95% CI) were 1.92 (1.13 to 3.24), 2.21 (1.32 to 3.69), 6.91 (4.22 to 11.30), 8.56 (5.15 to 14.22), and 10.73 (5.66 to 20.33); P=0.015, =0.002, <0.001, <0.001, and <0.001); after age and gender were adjusted, this trend still existed (1 to 5 components corresponding HR (95% CI) were 1.81(1.07 to 3.06), 1.95(1.16 to 3.27), 5.64(3.42 to 9.32), 6.69(3.97 to 11.25), and 7.76(4.04 to 14.91); P=0.028, =0.012, <0.001, <0.001, and <0.001). Conclusion:MS and its components can increase the risk of cholecystolithiasis and gallbladder polyp, and the risk of cholecystolithiasis and gallbladder polyp significantly increases along with the increase of accumulated of MS components.

OBJECTIVE To investigate the causal association between ticagrelor and risk of infection METHODS Two-sample Mendelian randomization was adopted. Genetic instrumental variables were selected based on the results of the largest genome-wide association analysis to in vivo exposure of ticagrelor and its major active metabolite AR-C124910XX. The causal associations of ticagrelor and its major active metabolite AR-C124910XX with drug indications （coronary artery disease， unstable angina pectoris， myocardial infarction， stroke and ischemic stroke）were analyzed by inverse variance weighted Mendelian randomization model as a positive control for genetic instrumental variables. The causal relationship between ticagrelor and bacterial infection， acute lower respiratory infection， bacterial pneumoniae， pneumoniae，acute upper respiratory infection and sepsis were furtheranalyzed by using this method， and the robustness of the results was assessed by using heterogeneity tests and horizontal 202002030415） pleiotropy tests. RESULTS The increase of area under the curve at steady state （AUCss） of the genetic surrogated ticagrelor significantly reduced the risk of coronary artery disease， myocardial infarction and unstable angina pectoris （P＜0.001）. AUCss genetic instrument variables of its main active metabolite AR-C124910XX failed to pass positive control. Further analysis showed that the increase of the genetic surrogated ticagrelor exposure suggestively reduced the risk of bacterial infection [OR（95%CI）＝0.80（0.65，0.99），P＝0.040] and sepsis [OR （95%CI）＝0.84（0.73， 0.98）， P＝0.023]. The results of the heterogeneity tests showed that there was no heterogeneity in the causal association of the genetic surrogated ticagrelor AUCss with bacterial infection and sepsis （P＞0.05）. The results of horizontal pleiotropy tests showed that the causal association of genetic surrogated ticagrelor AUCss with bacterial infection and sepsis had no effects on horizontal pleiotropy （P＞0.05）. CONCLUSIONS Ticagrelor has a potential role in reducing the risk of sepsis and bacterial infections.