ObjectiveTo investigate the effect of solute carrier family 7 member 5 (SLC7A5) inhibitor JPH203 on renal fibrosis induced by unilateral ureteral obstruction in mice. MethodsSixteen SPF male C57BL/6 mice were randomly divided into the control group and the experimental group, with 8 mice in each group. The mouse model of renal fibrosis was established by unilateral ureteral obstruction. From the third day after surgery, the mice in the control group were intraperitoneally injected with phosphate-buffered saline (PBS) for 11 consecutive days, and the injection dose was 200 μL/d. Mice in the experimental group received intraperitoneal injection of JPH203 (50 mg/kg) every day for 11 days. On day 14, the mice were euthanized, then the kidney tissues were obtained. Hematoxylin and eosin (HE) staining was used to assess renal tissue damage, Masson staining was used to evaluate collagen fiber deposition in the extracellular matrix, and immunohistochemistry was used to detect the levels of fibroblast activation markers α-smooth muscle actin (α-SMA) and collagen type Ⅰ (COL-Ⅰ) in kidney tissues. Western blotting was further performed to measure the expression levels of SLC7A5 and transforming growth factor-β1 (TGF-β1), as well as the phosphorylation levels of mammalian target of rapamycin complex 1 (mTORC1) signaling pathway-related molecules. Real-time quantitative PCR was used to verify changes in the mRNA levels of SLC7A5, α-SMA, and COL-Ⅰ in kidney tissues. ResultsCompared with the control group, the experimental group showed reduced destruction of renal tissue structure and a significantly lower pathological injury score (P<0.05). Additionally, collagen deposition in the extracellular matrix was decreased, and the percentage of collagen fiber area was significantly reduced (P<0.001) in the experimental group. The levels of fibroblast activation markers α-SMA and COL-Ⅰ were significantly lower in the experimental group (both P<0.001). The expression levels of SLC7A5 and TGF-β1 were also significantly decreased (P<0.001), and the phosphorylation levels of mTORC1 signaling pathway-related proteins 4E-BP1 and mTORC1 were significantly reduced (P<0.001). Real-time quantitative PCR confirmed that the mRNA levels of SLC7A5, α- SMA, and COL-Ⅰ in kidney tissues were significantly lower in the experimental group (P<0.001). ConclusionJPH203 may inhibit the progression of renal fibrosis in mice by suppressing SLC7A5 expression, regulating the mTORC1 signaling pathway, and altering fibroblast activation status.

This study aims to investigate the scientificity and efficacy of the compatibility of Jinlingzi San from pharmacokinetics. Liquid chromatography-tandem mass spectrometry(LC-MS/MS) was utilized to determine the plasma concentrations of the active components: toosendanin, tetrahydropalmatine A, and tetrahydropalmatine B at various time points following the gavage of Jinlingzi San and its single medicines in rats. Subsequently, WinNonlin was employed to calculate pertinent pharmacokinetic parameters. The pharmacokinetic parameters in rat plasma were compared between the single medicines and the compound formula of Jinlingzi San. It was discovered that the area under the curve(AUC_(all)) and peak concentrations(C_(max)) of tetrahydropalmatine A, and tetrahydropalmatine B were significantly elevated in the compound formula group compared with the single medicine groups. Conversely, the AUC_(all )and C_(max) of toosendanin notably decreased. Furthermore, the compound formula group had longer mean residence time(MRT) and lower apparent clearance(CL/F) of all three active ingredients than the single medicine groups(P<0.05). These findings indicated that Jinlingzi San enhanced the absorption of tetrahydropalmatine A and tetrahydropalmatine B in vivo, facilitating their pharmacological actions. Concurrently, it inhibited the absorption of toosendanin, thereby preventing potential toxic reactions. Moreover, the compatibility prolonged the residence time of the active ingredients in the body. This study provides a reference for exploring the compatibility rationality of Jinlingzi San.
Animals ; Rats ; Tandem Mass Spectrometry/methods* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rats, Sprague-Dawley ; Chromatography, Liquid/methods* ; Berberine Alkaloids/blood* ; Liquid Chromatography-Mass Spectrometry

OBJECTIVES: To evaluate the causal association between circulating levels of zinc, magnesium, and other minerals and autism spectrum disorder (ASD). METHODS: A two-sample Mendelian randomization (MR) analysis was performed using summary statistics from large-scale genome-wide association studies of European populations, including 18 382 ASD cases and 27 969 controls. Genetic data for iron, calcium, and magnesium were obtained from the UK Biobank, and data for zinc and selenium were sourced from an Australian-British cohort. A total of 351 genetic instrumental variables were selected. Causal inference was performed using inverse-variance weighting as the primary analysis method. Sensitivity analyses were performed by Cochran's Q test and MR-PRESSO global test to assess the robustness of the findings. RESULTS: No statistically significant causal effect was observed for circulating zinc, magnesium, calcium, selenium, or iron levels on ASD risk (all P>0.05). The odds ratios and 95% confidence intervals from the inverse-variance weighting analysis were 0.934 (0.869-1.003) for zinc, 1.315 (0.971-1.850) for magnesium, 1.055 (0.960-1.159) for calcium, 1.015 (0.953-1.080) for selenium, and 0.946 (0.687-1.303) for iron. Sensitivity analysis revealed significant heterogeneity in the causal association between circulating calcium and ASD (P=0.006), while the effect estimate remained stable after MR-PRESSO correction (P=0.487). The causal effect estimates for the remaining minerals demonstrated good robustness. CONCLUSIONS This study did not find significant evidence supporting a causal association between circulating zinc, magnesium, calcium, selenium, or iron levels and ASD risk, providing important clues for the etiology of ASD and precision nutritional interventions.
Humans ; Mendelian Randomization Analysis ; Autism Spectrum Disorder/genetics* ; Magnesium/blood* ; Zinc/blood* ; Minerals/blood* ; Genome-Wide Association Study ; Selenium/blood*

Objective:To investigate the longitudinal patterns and influencing factors of platelet counts among healthy adults in Sichuan Province from 2010 to 2021, and to inform the establishment of region-specific reference intervals for platelet counts.Methods:This study is a retrospective study. A total of 7 808 healthy adults who underwent annual physical examinations at West China Hospital, Sichuan University, between January 2010 and December 2021 were included. All participants were permanent Chengdu residents and completed consecutive complete blood count tests. Group-based trajectory modeling (GBTM) was used to identify distinct trajectories of platelet count over the ten-year period. One-way analyses were then conducted to compare baseline demographic characteristics (sex and age) among the different trajectory groups.Results:Among 7 808 participants, 4 589 (58.8%) were male and 3 219 (41.2%) were female. Four platelet count trajectories were identified by GBTM: steadily increasing group [27.4% (2 139/7 808)], early increase-plateau group [44.1% (3 445/7 808)], early decrease-subsequent increase group [5.4% (422/7 808)], and steadily decreasing group [23.1% (1 802/7 808)], with an average growth rate of 3.3%, 1.6%, 0.7%, and -0.6%, respectively. There were statistically significant differences in both sex and age distributions among the four trajectory groups. Sex-distribution differed significantly across the four trajectory groups ( χ2=73.3, P<0.001). The male proportions in the four trajectory groups were 59.6% (1 275/2 139), 62.8% (2 165/3 445), 48.1% (203/422), and 52.5% (946/1 802), respectively. The baseline ages were 45 (36, 55), 43 (35, 53), 50 (40, 60), and 47 (39, 58) years, respectively (H=121.0, P<0.001). Conclusions:Healthy adults in Sichuan Province exhibit four longitudinal trajectories of platelet counts: steadily increasing, early increase-plateau, early decrease-subsequent increase, and steadily decreasing. The two trajectories characterized by rising platelet counts (steadily increasing group and early increase-plateau group) exhibited higher male predominance and lower median ages, whereas the early decrease-subsequent increase group and the steadily decreasing group exhibited lower male proportions and higher median ages. Therefore, while establishing reference intervals and developing health management strategies for platelet counts, it is essential to account for the sex, age characteristics and the population′s dynamic changes.

Objective:To investigate the longitudinal patterns and influencing factors of platelet counts among healthy adults in Sichuan Province from 2010 to 2021, and to inform the establishment of region-specific reference intervals for platelet counts.Methods:This study is a retrospective study. A total of 7 808 healthy adults who underwent annual physical examinations at West China Hospital, Sichuan University, between January 2010 and December 2021 were included. All participants were permanent Chengdu residents and completed consecutive complete blood count tests. Group-based trajectory modeling (GBTM) was used to identify distinct trajectories of platelet count over the ten-year period. One-way analyses were then conducted to compare baseline demographic characteristics (sex and age) among the different trajectory groups.Results:Among 7 808 participants, 4 589 (58.8%) were male and 3 219 (41.2%) were female. Four platelet count trajectories were identified by GBTM: steadily increasing group [27.4% (2 139/7 808)], early increase-plateau group [44.1% (3 445/7 808)], early decrease-subsequent increase group [5.4% (422/7 808)], and steadily decreasing group [23.1% (1 802/7 808)], with an average growth rate of 3.3%, 1.6%, 0.7%, and -0.6%, respectively. There were statistically significant differences in both sex and age distributions among the four trajectory groups. Sex-distribution differed significantly across the four trajectory groups ( χ2=73.3, P<0.001). The male proportions in the four trajectory groups were 59.6% (1 275/2 139), 62.8% (2 165/3 445), 48.1% (203/422), and 52.5% (946/1 802), respectively. The baseline ages were 45 (36, 55), 43 (35, 53), 50 (40, 60), and 47 (39, 58) years, respectively (H=121.0, P<0.001). Conclusions:Healthy adults in Sichuan Province exhibit four longitudinal trajectories of platelet counts: steadily increasing, early increase-plateau, early decrease-subsequent increase, and steadily decreasing. The two trajectories characterized by rising platelet counts (steadily increasing group and early increase-plateau group) exhibited higher male predominance and lower median ages, whereas the early decrease-subsequent increase group and the steadily decreasing group exhibited lower male proportions and higher median ages. Therefore, while establishing reference intervals and developing health management strategies for platelet counts, it is essential to account for the sex, age characteristics and the population′s dynamic changes.

This paper reports a case of a 59-year-old female patient who presented with sudden aphasia and left-sided weakness.After emergency cerebral angiography and intracranial artery thrombectomy,the left subclavian artery was accidentally punctured during left subclavian vein catheterization.Three-dimensional reconstruction and preoperative simulation using Mimics software and 3dsMAX were performed to determine the subcutaneous tunnel length and the applicability of the Angioseal closure device.Preoperative simulation showed a tunnel length of 74.6 mm,satisfying the condition of subcutaneous tunnel＜compression tube＜Angioseal introducer.Angioseal closure was then performed.Postoperative angiography showed satisfactory occlusion,and the patient had no complications.This paper discusses the challenges in managing accidental subclavian artery punctures and the application conditions of the Angioseal closure device,emphasizing the importance of preoperative three-dimensional reconstruction and simulation for ensuring surgical success.For accidental subclavian artery punctures with tunnel lengths not exceeding 88 mm,the Angioseal closure device is a safe and effective method.

This paper reports a case of a 59-year-old female patient who presented with sudden aphasia and left-sided weakness.After emergency cerebral angiography and intracranial artery thrombectomy,the left subclavian artery was accidentally punctured during left subclavian vein catheterization.Three-dimensional reconstruction and preoperative simulation using Mimics software and 3dsMAX were performed to determine the subcutaneous tunnel length and the applicability of the Angioseal closure device.Preoperative simulation showed a tunnel length of 74.6 mm,satisfying the condition of subcutaneous tunnel＜compression tube＜Angioseal introducer.Angioseal closure was then performed.Postoperative angiography showed satisfactory occlusion,and the patient had no complications.This paper discusses the challenges in managing accidental subclavian artery punctures and the application conditions of the Angioseal closure device,emphasizing the importance of preoperative three-dimensional reconstruction and simulation for ensuring surgical success.For accidental subclavian artery punctures with tunnel lengths not exceeding 88 mm,the Angioseal closure device is a safe and effective method.

Hypertension and osteoporosis(OP)are common diseases in middle-aged and elderly people,and the number of patients with both diseases has gradually increased in recent years.Because the onset of the disease is hidden,it is easy to cause fractures and serious complications of heart,brain and kidney in the later stage,which not only seriously damages the quality of life of patients,but also increases the difficulty of clinical treatment.Therefore,it is particularly necessary to strengthen the research on this disease.More and more studies have found that the disorder of intestinal flora will lead to the occurrence of OP,while the intestinal flora of patients with hypertension is obviously out of balance.Therefore,this paper thinks that intestinal flora may be the key influencing factor of hypertension complicated with OP,and the imbalance of intestinal flora will lead to the imbalance of short-chain fatty acid metabolism,immune inflammatory reaction and increased sympathetic nerve activity,thus causing the imbalance of bone homeostasis and promoting the occurrence of OP.Therefore,it is suggested that regulating intestinal flora may be a new way to intervene hypertension complicated with OP.

Objective:To evaluate knee biomechanics of patients about 12 months after anterior cruciate ligament(ACL)reconstruction during cutting and determine the abnormal biomechanical characteristics.Methods:Sixteen males about 12 months after ACL reconstruction were recruited for this study.Three-dimensional kinematic and kinetic data were collected during cutting movement.Knee joint angles and moments were calculated.Paired t-tests were used to compare the differences in knee biomechanics be-tween the surgical leg and nonsurgical leg.Results:The peak posterior ground reaction force(surgical leg:0.380±0.071;nonsurgical leg:0.427±0.069,P=0.003)and vertical ground reaction force(surgical leg:1.996±0.202,nonsurgical leg:2.110±0.182,P=0.001)were significantly smaller in the surgical leg than in the nonsurgical leg.When compared with the uninjured leg,the surgical leg demonstrated a smaller knee flexion angle(surgical leg:38.3°±7.4°;nonsurgical leg:42.8°±7.9°,P＜0.001)and larger external rotation angle(surgical leg:10.3°±2.4°;nonsurgical leg:7.7°±2.1°,P=0.008).The surgical leg also demonstrated a smaller peak knee extension moment(surgical leg:0.092±0.031;nonsurgical leg:0.133±0.024,P＜0.001)and peak knee external rotation moment(surgical leg:0.005±0.004;nonsurgical leg:0.008±0.004,P=0.015)when com-pared with the nonsurgical leg.Conclusion:The individuals with ACL reconstruction mainly showed asymmetrical movements in the sagittal and horizontal planes.The surgical leg demonstrated a smaller peak knee flexion angle,knee extension moment,and knee external rotation moment,with greater knee external rotation angle.

Objective:To understand the symptoms of diarrhea of residents in Tianjin and their willingness to vaccinate, to provide reference for health education, prevention and control of infectious diarrhea.Methods:Cross-sectional study design was adopted. From September to December 2023, a questionnaire survey was conducted among some residents as subjects in Nankai District, Beichen District, Baodi District and Binhai Area of Tianjin by multistage stratified cluster random sampling,to collect information such as sociodemographic characteristics, diarrhea symptoms and vaccination intention. According to the formula n=[ u2απ (1 - π)]/ δ2, the estimated sample size was 3 458 cases. The logistic regression model was used to analyze the factors related to the willingness of the respondents to receive diarrhea vaccination. The software SPSS 24.0 was used for statistical analysis. Results:A total of 3 808 subjects were investigated, with the male-to-female ratio as 1∶1.11 (1 806∶2 002), the age was (42.48±21.59) years old, and the education level of middle school or below accounted for 50.84% (1 936/3 808). The incidence rate of diarrhea was 18.28% (696/3 808), and 48.84% (1 860/3 808) were willing to be vaccinated with diarrhea vaccine. The results of multivariate logistic regression analysis showed that the age was 15-59 years old and ≥60 years old (a OR=2.31, 95% CI:1.80-2.96; a OR=1.66, 95% CI:1.38-2.00), lived in Binhai Area (a OR=2.09, 95% CI:1.62-2.71), and those who knew that community health service centers can provide the vaccination (a OR=1.61,95% CI:1.34-1.92), those who walked from the address to the community health service center were less than 15 minutes (a OR=1.54, 95% CI:1.28-1.85), those who often travel or on business (a OR=1.36, 95% CI:1.07-1.73), and those who actively obtained health care information related to diarrhea prevention when going abroad (a OR=1.69,95% CI:1.43-1.98) were more willing to be vaccinated against diarrhea. Conclusions:The incidence of diarrhea symptoms of residents was slightly higher in Tianjin, but they were less willing to be vaccinated against diarrhea. People who often go outside and go abroad were more willing to be vaccinated against diarrhea. It is suggested that the popular science propaganda and health education of diarrhea vaccine should be effectively carried out by using network platform in community.