Background Work-related musculoskeletal disorders (WMSDs) are a major occupational health concern, particularly among workers exposed to adverse ergonomic conditions. Manganese production involves heavy physical demands, yet research on WMSDs among manganese workers remains limited. Objective To investigate the prevalence and influencing factors of WMSDs among manganese workers in a manganese enterprise in Guangxi. Methods A cross-sectional survey was conducted from May to June 2024 on workers at a manganese factory in Guangxi. The Chinese Musculoskeletal Disorders Questionnaire was used to collect information on demographic characteristics, distribution of musculoskeletal symptoms, and work-related exposures. χ² test was applied to compare differences in positive WMSDs rates across groups, and logistic regression analysis was performed to identify associated factors. Results A total of 1476 workers were enrolled in the study after pre-determined inclusion and exclusion criteria. The overall prevalence of WMSDs was 34.15%. The most commonly affected body regions were the lower back (17.28%), neck (16.67%), and shoulders (13.82%). The results of logistic regression analysis indicated that female, older age, and education level of college or above were associated with a higher risk of WMSDs (P<0.05). Awkward working postures were significantly associated with WMSDs in corresponding body regions; in particular, awkward postures of the neck, upper limbs, trunk, and lower limbs were related to an increased risk of WMSDs in multiple body sites (P<0.05). In addition, poor lighting conditions, high workplace temperature, frequent or sustained arm support during work, and high job demands were associated with an increased risk of overall or site-specific WMSDs (P<0.05). Conclusion The high prevalence of WMSDs among manganese workers is closely associated with demographic characteristics, working postures, and work environment and organizational factors. Targeted ergonomic interventions focusing on high-risk body regions and key ergonomic exposures are warranted to reduce the risk of WMSDs among manganese workers.

OBJECTIVE: To observe the effect of moxibustion on small intestinal mucosal immune barrier in rats with diarrhea-predominant irritable bowel syndrome (IBS-D) and explore its underlying mechanisms. METHODS: Of 38 newborn rats from 4 healthy SPF pregnant rats, 12 neonatal rats were randomly selected in a normal group. IBS-D model was prepared by the combined measures for the rest rats, including neonatal maternal separation, acetic acid enema and chronic restraint stress. Twenty-four successfully-modeled rats were randomized into a model group and a moxibustion group, 12 rats in each one. In the moxibustion group, suspending moxibustion was delivered at bilateral "Tianshu" (ST25) and "Shangjuxu" (ST37), 20 min each time, once daily and for 7 consecutive days. Separately, before acetic acid enema (aged 35 days), after modeling (aged 45 days) and after intervention (aged 53 days), the body mass, loose stool rate (LSR) and and the minimum volume threshold when abdominal withdrawal reflex (AWR) scored 3 were observed in the rats of each group. After intervention (aged 53 days), using HE and PAS staining, the morphology of duodenum was observed, the length of villus and the depth of crypt were measured, the ratio of the length of villus to the depth of crypt was calculated; and the numbers of mucosal intraepithelial lymphocytes (IELs) and goblet cells were counted. With ELISA adopted, the contents of γ-interferon (IFN-γ), interleukin-4 (IL-4) and secretory immunoglobulin A (sIgA) in duodenal mucosa of rats were detected. The proportion of T cell subsets in duodenal mucosa was detected using flow cytometry. The microvilli and tight junctions of duodenal mucosal epithelial cells were observed by transmission electron microscopy, and the integrity of duodenal mucosa observed by scanning electron microscopy. RESULTS: Compared with the normal group, for the rats in the model group, the body mass, the minimum volume threshold when AWR scored 3, the length of duodenal villus and the the ratio of the length of villus to the depth of crypt, as well as the proportion of CD₈⁺ T subset were all reduced (P<0.01, P<0.05), the counts of goblet cells in duodenal mucosa decreased (P<0.01); LRS, the proportion of CD₄⁺ T subset and CD₄⁺/CD₈⁺, as well as the contents of IFN-γ, IL-4 and sIgA in duodenal mucosa and IFN-γ/IL-4 were all elevated (P<0.01); and the numbers of IELs rose (P<0.01). The morphology of duodenal mucosa was irregular, the villi got shorter, sparse and scattered, with uneven density. The morphology of epithelial cells was destroyed and the tight junctions damaged, with larger spaces. When compared with the model group, in the moxibustion group, the body mass, the minimum volume threshold when AWR scored 3, the length of duodenal villus and the ratio of the length of villus to the depth of crypt, as well as the counts of goblet cells in duodenal mucosa increased (P<0.01); LRS, the proportion of CD₄⁺ T subset, and CD₄⁺/CD₈⁺, as well as the contents of IFN-γ, IL-4 and sIgA in duodenal mucosa and IFN-γ/IL-4 were reduced (P<0.01); and the numbers of IELs was dropped (P<0.01). The morphology of duodenal mucosa was more regular, the villi were grew, got longer and arranged regularly, with even density. The morphology of epithelial cells was slightly destroyed, and the tight junctions partially damaged. CONCLUSION Moxibustion at "Tianshu" (ST25) and "Shangjuxu" (ST37) can reduce visceral hypersensitivity in IBS-D rats and relieve abdominal pain, diarrhea and other symptoms. Its effect mechanism may be related to the repair of small intestinal mucosal immune barrier and the improvement in the immune function in IBS-D.
Animals ; Irritable Bowel Syndrome/immunology* ; Rats ; Moxibustion ; Intestinal Mucosa/immunology* ; Female ; Diarrhea/therapy* ; Intestine, Small/immunology* ; Male ; Humans ; Rats, Sprague-Dawley ; Disease Models, Animal

Objective:To compare the clinical efficacy of robot-assisted balloon tibioplasty and traditional open reduction and internal fixation in the treatment of AO/OTA type 41B2 tibial plateau fracture.Methods:A retrospective cohort study was conducted to analyze the clinical data of 70 patients with AO/OTA type 41B2 tibial plateau fracture who were admitted to Wuhan Fourth Hospital from September 2019 to October 2022, including 35 males and 35 females, aged 24-62 years [(44.9±9.5)years]. Among them, 41 patients underwent traditional open reduction and internal fixation (open reduction group), while 29 patients underwent robot-assisted balloon tibioplasty (balloon group). The following parameters were compared between the two groups: incision length, operative blood loss, number of intraoperative fluoroscopies, operation duration, and length of hospital stay; Rasmussen radiological scores at 3 days, 3 months postoperatively, and at the last follow-up and the fracture healing time; pain visual analogue scale (VAS) scores preoperatively, and at 2 days and 3 months postoperatively; knee joint range of motion at 5 days, 3 months postoperatively, and at the last follow-up; Hospital for Special Surgery (HSS) knee function scores at 3, 6 months postoperatively, and at the last follow-up; incidence rate of complications at 15 days postoperatively.Results:All the patients were followed for 12-24 months [18(17, 20)months]. The incision length, operative blood loss and length of hospital stay in the balloon group were 1.6(1.5, 3.0)cm, 5.0(5.0, 5.0)ml and 11.0(9.0, 14.0)days, less than those in the open reduction group [12.0(11.0, 12.0)cm, 100.0(50.0, 120.0)ml and 15.0(13.0, 20.0)days] ( P<0.01). The number of intraoperative fluoroscopies and operation duration in the open reduction group were 9.0(7.0, 10.0)times and 75.0(60.0, 90.0)minutes, less than those in the balloon group [336.0(335.0, 340.0)times and [90.0(70.0, 105.0)minutes] ( P<0.05). There were no significant differences in the Rasmussen radiological scores between the two groups at 3 days, 3 months postoperatively, or at the last follow-up ( P>0.05). The fracture healing time in the balloon group was 3.0(3.0, 3.0)months, shorter than 3.0(3.0, 3.5)months in the open reduction group ( P<0.05). No significant differences were observed between the two groups in VAS scores before operation or at 3 months postoperatively ( P>0.05). However, the VAS score was 2.0(2.0, 3.0)points at 2 days postoperatively in the balloon group, lower than 5.0(5.0, 6.0)points in the open reduction group ( P<0.01). The knee joint range of motion at 5 days, 3 months postoperatively and at the last follow-up were 90.0(85.0, 90.0)°, 135.0(130.0, 135.0)° and 140.0(135.0, 140.0)° in the balloon group, better than 65.0(60.0, 70.0)°, 125.0(120.0, 130.0)°, 130.0(130.0, 140.0)° in the open reduction group ( P<0.01). Similarly, the HSS knee function scores at 3, 6 months postoperatively and at the last follow-up were 80.0(80.0, 81.0)points, 91.0(90.0, 92.0)points, and 95.0(93.0, 96.0)points in the balloon group, better than 71.0(70.0, 72.0)points, 83.0(81.0, 84.0)points, and 86.0(84.0, 88.0)points in the open reduction group ( P<0.01). The incidence rate of complications in the balloon group was 0, comparable to 12% (5/41) in the open reduction group ( P>0.05). Conclusion:Compared with traditional open reduction and internal fixation surgery, robot-assisted balloon tibioplasty in the treatment of AO/OTA type 41B2 tibial plateau fracture significantly reduces surgical trauma, alleviates postoperative pain, promotes fracture healing, and accelerates functional recovery of the affected limbs.

Hungary, as the first European country to legislate TCM, its legislation experience has significant implications for the international development of TCM. This article reviewed the historical process of TCM legislation in Hungary, summarized its legislative achievements, and analyzed the problems encountered during the implementation process. It was found that the current challenges faced by TCM legislation in Hungary mainly include constraints from the dominance of modern medicine, restrictions from strict qualification requirements, insufficient public awareness, difficulties in TCM registration, and challenges in policy coordination and cooperation. Based on these findings, the article proposed countermeasures such as improving the legal framework, strengthening educational cooperation, enhancing public awareness, promoting the mutual recognition of standards between China and Europe, and deepening China-Hungary collaboration. These measures aim to further improve the legislation and implementation of TCM in Hungary, thereby promoting the healthy development of TCM in Hungary and the global service trade of TCM.

Objective:To compare the clinical efficacy of robot-assisted balloon tibioplasty and traditional open reduction and internal fixation in the treatment of AO/OTA type 41B2 tibial plateau fracture.Methods:A retrospective cohort study was conducted to analyze the clinical data of 70 patients with AO/OTA type 41B2 tibial plateau fracture who were admitted to Wuhan Fourth Hospital from September 2019 to October 2022, including 35 males and 35 females, aged 24-62 years [(44.9±9.5)years]. Among them, 41 patients underwent traditional open reduction and internal fixation (open reduction group), while 29 patients underwent robot-assisted balloon tibioplasty (balloon group). The following parameters were compared between the two groups: incision length, operative blood loss, number of intraoperative fluoroscopies, operation duration, and length of hospital stay; Rasmussen radiological scores at 3 days, 3 months postoperatively, and at the last follow-up and the fracture healing time; pain visual analogue scale (VAS) scores preoperatively, and at 2 days and 3 months postoperatively; knee joint range of motion at 5 days, 3 months postoperatively, and at the last follow-up; Hospital for Special Surgery (HSS) knee function scores at 3, 6 months postoperatively, and at the last follow-up; incidence rate of complications at 15 days postoperatively.Results:All the patients were followed for 12-24 months [18(17, 20)months]. The incision length, operative blood loss and length of hospital stay in the balloon group were 1.6(1.5, 3.0)cm, 5.0(5.0, 5.0)ml and 11.0(9.0, 14.0)days, less than those in the open reduction group [12.0(11.0, 12.0)cm, 100.0(50.0, 120.0)ml and 15.0(13.0, 20.0)days] ( P<0.01). The number of intraoperative fluoroscopies and operation duration in the open reduction group were 9.0(7.0, 10.0)times and 75.0(60.0, 90.0)minutes, less than those in the balloon group [336.0(335.0, 340.0)times and [90.0(70.0, 105.0)minutes] ( P<0.05). There were no significant differences in the Rasmussen radiological scores between the two groups at 3 days, 3 months postoperatively, or at the last follow-up ( P>0.05). The fracture healing time in the balloon group was 3.0(3.0, 3.0)months, shorter than 3.0(3.0, 3.5)months in the open reduction group ( P<0.05). No significant differences were observed between the two groups in VAS scores before operation or at 3 months postoperatively ( P>0.05). However, the VAS score was 2.0(2.0, 3.0)points at 2 days postoperatively in the balloon group, lower than 5.0(5.0, 6.0)points in the open reduction group ( P<0.01). The knee joint range of motion at 5 days, 3 months postoperatively and at the last follow-up were 90.0(85.0, 90.0)°, 135.0(130.0, 135.0)° and 140.0(135.0, 140.0)° in the balloon group, better than 65.0(60.0, 70.0)°, 125.0(120.0, 130.0)°, 130.0(130.0, 140.0)° in the open reduction group ( P<0.01). Similarly, the HSS knee function scores at 3, 6 months postoperatively and at the last follow-up were 80.0(80.0, 81.0)points, 91.0(90.0, 92.0)points, and 95.0(93.0, 96.0)points in the balloon group, better than 71.0(70.0, 72.0)points, 83.0(81.0, 84.0)points, and 86.0(84.0, 88.0)points in the open reduction group ( P<0.01). The incidence rate of complications in the balloon group was 0, comparable to 12% (5/41) in the open reduction group ( P>0.05). Conclusion:Compared with traditional open reduction and internal fixation surgery, robot-assisted balloon tibioplasty in the treatment of AO/OTA type 41B2 tibial plateau fracture significantly reduces surgical trauma, alleviates postoperative pain, promotes fracture healing, and accelerates functional recovery of the affected limbs.

Objective:To compare the efficacy of radial forearm flap and anterolateral thigh flap in repairing soft tissue defects after oral cancer surgery and to explore their indications.Methods:A retrospective analysis was conducted on clinical data of patients with oral cancer treated at the Department of Stomatology, Affiliated Hospital of Nantong University, from May 2019 to February 2023. Patients were divided into two groups based on the repair method: the radial forearm flap group and the anterolateral thigh flap group. The groups were compared in the following aspects. (1) Surgical parameters including defect area after oral cancer resection, flap area, flap preparation time, operation time, and length of hospital stay. (2) Inflammatory markers (interleukin-6 and C-reactive protein levels) measured 1 day before surgery and 1 day after surgery. (3) Flap survival rate was calculated. (4) Complication rates was calculated in the flap donor area and infection rates in the oral recipient area within 6 months postoperatively. (5) Six months postoperatively, the patient’s oral function was assessed by a physician using the University of Washington quality of life scale (UW-QOL). The evaluation included assessments of oral opening, speech, and eating functions. Each parameter was scored on a scale of 0 to 10 (higher scores indicated better recovery). (6) Quality of life was assessed using the 36-item short form health survey scale(SF-36) at 2, 4 and 6 months postoperatively, with scores ranging from 0 to 100 (higher scores indicated better quality of life). (7) Patient satisfaction was assessed at 6 months postoperatively, with satisfaction levels categorized as satisfied, basically satisfied, and dissatisfied. The satisfaction rate was calculated as (satisfied + basically satisfied ) cases / total cases in each group × 100%. Statistical analysis was performed using SPSS 22.0. Measurement data were expressed as Mean±SD, and comparisons between groups were conducted using t-tests. Count data were expressed as cases and (or) percentages, and comparisons were made using chi-square test. P<0.05 was considered statistically significant. Results:The radial forearm flap group included 48 cases (32 males, 16 females), aged (49.3±5.0) years, with a body mass index (BMI) of (23.0±1.1) kg/m 2 and a disease course of (6.5±2.1) months. The group had 21 cases of tongue cancer, 12 of floor of mouth cancer, and 15 of buccal cancer, including 40 squamous cell carcinomas and 8 basal cell carcinomas. The anterolateral thigh flap group included 32 cases (20 males, 12 females), aged (50.1±5.0) years, with a BMI of (23.0±1.0) kg/m 2 and a disease course of (7.0±2.2) months. The group had 16 cases of tongue cancer, 7 cases of floor of mouth cancer, and 9 cases of buccal cancer, including 27 squamous cell carcinomas and 5 basal cell carcinomas. There were no significant differences in gender, age, BMI, disease course, tumor location, or pathological type between the two groups ( P>0.05). The defect area after oral cancer resection was smaller in the radial forearm flap group[ (39.0±1.3) cm 2 ] compared to the anterolateral thigh flap group[ (40.3±2.2) cm 2] ( t=3.32, P=0.001). There were no significant differences in flap area, flap preparation time, or length of hospital stay between the two groups ( P>0.05). The operation time was shorter in the radial forearm flap group [(5.1±1.1) h] compared to the anterolateral thigh flap group [(6.8±2.8) h] ( t=0.26, P<0.001). There were no significant differences in interleukin-6 and C-reactive protein levels between the two groups 1 day before surgery and 1 day after surgery ( P>0.05). The flap survival rates were 97.9% (47/48) in the radial forearm flap group and 93.8% (30/32) in the anterolateral thigh flap group, with no significant difference( P>0.05). Postoperative donor site complications mainly included infection, pigmentation, itching, etc. The overall incidence of complications in the donor site of the radial forearm flap [33.3% (16/48)] was higher than that in the anterolateral thigh flap group [12.5% (4/32)], and the difference was statistically significant ( χ2=4.44, P=0.035). There was no significant difference in infection rates in the oral recipient area between the two groups ( P>0.05). Six months postoperatively, the average scores for oral opening, speech, and eating functions were above 7 in both groups, with no significant differences ( P>0.05). Quality of life scores improved over time in both groups, with average scores above 90 at 6 months postoperatively, and no significant differences at any time point ( P>0.05). The patient satisfaction rate was 91.7% (44/48) in the radial forearm flap group and 90.6% (29/32) in the anterolateral thigh flap group, with no significant difference ( P>0.05). Conclusion:Both radial forearm flap and anterolateral thigh flap can effectively repair soft tissue defects after oral cancer resection, significantly improving patients’oral function. The anterolateral thigh flap provides sufficient tissue volume and is suitable for patients with larger defect areas. The radial forearm flap is suitable for patients with a smaller defect area after oral cancer resection. Its surgical procedure is relatively less complex and offers an advantage in reducing surgery time. However, the donor site complications are higher with the radial forearm flap compared to the anterolateral thigh flap.

Objective:To compare the efficacy of radial forearm flap and anterolateral thigh flap in repairing soft tissue defects after oral cancer surgery and to explore their indications.Methods:A retrospective analysis was conducted on clinical data of patients with oral cancer treated at the Department of Stomatology, Affiliated Hospital of Nantong University, from May 2019 to February 2023. Patients were divided into two groups based on the repair method: the radial forearm flap group and the anterolateral thigh flap group. The groups were compared in the following aspects. (1) Surgical parameters including defect area after oral cancer resection, flap area, flap preparation time, operation time, and length of hospital stay. (2) Inflammatory markers (interleukin-6 and C-reactive protein levels) measured 1 day before surgery and 1 day after surgery. (3) Flap survival rate was calculated. (4) Complication rates was calculated in the flap donor area and infection rates in the oral recipient area within 6 months postoperatively. (5) Six months postoperatively, the patient’s oral function was assessed by a physician using the University of Washington quality of life scale (UW-QOL). The evaluation included assessments of oral opening, speech, and eating functions. Each parameter was scored on a scale of 0 to 10 (higher scores indicated better recovery). (6) Quality of life was assessed using the 36-item short form health survey scale(SF-36) at 2, 4 and 6 months postoperatively, with scores ranging from 0 to 100 (higher scores indicated better quality of life). (7) Patient satisfaction was assessed at 6 months postoperatively, with satisfaction levels categorized as satisfied, basically satisfied, and dissatisfied. The satisfaction rate was calculated as (satisfied + basically satisfied ) cases / total cases in each group × 100%. Statistical analysis was performed using SPSS 22.0. Measurement data were expressed as Mean±SD, and comparisons between groups were conducted using t-tests. Count data were expressed as cases and (or) percentages, and comparisons were made using chi-square test. P<0.05 was considered statistically significant. Results:The radial forearm flap group included 48 cases (32 males, 16 females), aged (49.3±5.0) years, with a body mass index (BMI) of (23.0±1.1) kg/m 2 and a disease course of (6.5±2.1) months. The group had 21 cases of tongue cancer, 12 of floor of mouth cancer, and 15 of buccal cancer, including 40 squamous cell carcinomas and 8 basal cell carcinomas. The anterolateral thigh flap group included 32 cases (20 males, 12 females), aged (50.1±5.0) years, with a BMI of (23.0±1.0) kg/m 2 and a disease course of (7.0±2.2) months. The group had 16 cases of tongue cancer, 7 cases of floor of mouth cancer, and 9 cases of buccal cancer, including 27 squamous cell carcinomas and 5 basal cell carcinomas. There were no significant differences in gender, age, BMI, disease course, tumor location, or pathological type between the two groups ( P>0.05). The defect area after oral cancer resection was smaller in the radial forearm flap group[ (39.0±1.3) cm 2 ] compared to the anterolateral thigh flap group[ (40.3±2.2) cm 2] ( t=3.32, P=0.001). There were no significant differences in flap area, flap preparation time, or length of hospital stay between the two groups ( P>0.05). The operation time was shorter in the radial forearm flap group [(5.1±1.1) h] compared to the anterolateral thigh flap group [(6.8±2.8) h] ( t=0.26, P<0.001). There were no significant differences in interleukin-6 and C-reactive protein levels between the two groups 1 day before surgery and 1 day after surgery ( P>0.05). The flap survival rates were 97.9% (47/48) in the radial forearm flap group and 93.8% (30/32) in the anterolateral thigh flap group, with no significant difference( P>0.05). Postoperative donor site complications mainly included infection, pigmentation, itching, etc. The overall incidence of complications in the donor site of the radial forearm flap [33.3% (16/48)] was higher than that in the anterolateral thigh flap group [12.5% (4/32)], and the difference was statistically significant ( χ2=4.44, P=0.035). There was no significant difference in infection rates in the oral recipient area between the two groups ( P>0.05). Six months postoperatively, the average scores for oral opening, speech, and eating functions were above 7 in both groups, with no significant differences ( P>0.05). Quality of life scores improved over time in both groups, with average scores above 90 at 6 months postoperatively, and no significant differences at any time point ( P>0.05). The patient satisfaction rate was 91.7% (44/48) in the radial forearm flap group and 90.6% (29/32) in the anterolateral thigh flap group, with no significant difference ( P>0.05). Conclusion:Both radial forearm flap and anterolateral thigh flap can effectively repair soft tissue defects after oral cancer resection, significantly improving patients’oral function. The anterolateral thigh flap provides sufficient tissue volume and is suitable for patients with larger defect areas. The radial forearm flap is suitable for patients with a smaller defect area after oral cancer resection. Its surgical procedure is relatively less complex and offers an advantage in reducing surgery time. However, the donor site complications are higher with the radial forearm flap compared to the anterolateral thigh flap.

Objective:To discuss the effect of parthenolide(PTL)on the apoptosis of the chondrocytes under mechanical stretch stress by regulating the expression of piezo type mechanosensitive ion channel component 1(Piezo1),and to clarify the related mechanism.Methods:The chondrocytes were divided into 0%,5%,10%,15%,and 20%stretch groups according to the stretch variable.Additionally,the chondrocytes were divided into control group,20%stretch group,20%stretch+5 μmol·L-1 PTL group,20%stretch+10 μmol·L-1 PTL group,and 20%stretch+20 μmol·L-1 PTL group.The Piezo1 short hairpin RNA(shRNA)interference lentivirus(sh-Piezo1)or shRNA-NC lentivirus were used to infect the chondrocytes,and the chondrocytes were divided into sh-Piezo1 group and sh-NC group,and also set up blank control group.The chondrocytes were also devided into 20%stretch group,20%stretch+PTL group,20%stretch+sh-Piezo1 group,and 20%stretch+sh-Piezo1+PTL group.Hoechst 33258 fluorescence staining was used to observe the morphology of the nuclear in various groups;flow cytometry was used to detect the apoptotic rates of the cells in various groups;spectrophotometry was used to detect the cysteinyl aspartate specific proteinase(Caspase)-3 activities in the cells in various groups;CCK-8 method was used to detect the proliferation rates of the cells in various groups;Fluo-4/AM fluorescent probe method was used to detect the calicium ion(Ca2+)levels in the cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of Piezo1 mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Piezo1 protein in the cells in various groups.Results:The Hoechst 33258 fluorescence staining resuts showed that as the increasing of stretch,the number of the chondrocytes with fragmented and densely stained nuclei in 0%,5%,10%,15%,and 20%stretch groups were gradually increased.The flow cytometry results showed that compared with 0%stretch group,the apoptotic rates of the chondrocytes in 5%,10%,15%,and 20%stretch groups were significantly increased(P<0.01);compared with control group,the apoptotic rate of the chondrocytes in 20%stretch group was significantly increased(P<0.05);compared with 20%stretch group,the apoptotic rates of the chondrocytes in 20%stretch+5 μmol·L-1 PTL group,20%stretch+10 μmol·L-1 PTL group,and 20%stretch+20 μmol·L-1 PTL group were significantly decreased(P<0.05);compared with 20%stretch group,the apoptotic rates of chondrocytes in 20%stretch+PTL group and 20%stretch+sh-Piezo1 group were significantly decreased(P<0.05).The spectrophotometry results showed that compared with 0%stretch group,the Caspase-3 activities in the chondrocytes in 5%,10%,15%,and 20%stretch groups were significantly increased(P<0.01);compared with control group,the Caspase-3 activity in the chondrocytes in 20%stretch group was significantly increased(P<0.05);compared with 20%stretch group,the Caspase-3 activities in the chondrocytes in 20%stretch+5 μmol·L-1 PTL group,20%stretch+10 μmol·L-1 PTL group,and 20%stretch+20 μmol·L-1 PTL group were significantly decreased(P<0.05).Compared with 20%stretch group,the Caspase-3 activities in the chondrocytes in 20%stretch+PTL group and 20%stretch+sh-Piezo1 group were significantly decreased(P<0.05).The CCK-8 method results showed that compared with 0 μmol·L-1 PTL group,the proliferation rates of the chondrocytes in 40.00,80.00,and 160.00 μmol·L-1 PTL groups were significantly decreased(P<0.05),indicating that 20.00 μmol·L-1 PTL was the maximum non-toxic concentration.The Fluo-4/AM fluorescent probe method results showed that compared with control group,the Ca2+level in the chondrocytes in 20%stretch group was significantly increased(P<0.05);compared with 20%stretch group,the Ca2+levels in the chondrocytes in 20%stretch+5 μmol·L-1 PTL group,20%stretch+10 μmol·L-1 PTL group,and 20%stretch+20 μmol·L-1 PTL group were significantly decreased(P<0.05);compared with 20%stretch group,the Ca2+levels in the chondrocytes in 20%stretch+PTL group and 20%stretch+sh-Piezo1 group were significantly decreased(P<0.05).The RT-qPCR results showed that compared with blank control group and sh-NC group,the expression level of Piezo1 mRNA in the chondrocytes in sh-Piezo1 group was significantly decreased(P<0.05).The Western blotting results showed that compared with control group,the expression levels of Piezo1 protein in the chondrocytes in 20%stretch group was significantly increased(P<0.05);compared with 20%stretch group,the expression levels of Piezo1 protein in the chondrocytes in 20%stretch+5 μmol·L-1 PTL group,20%stretch+10 μmol·L-1 PTL group,and 20%stretch+20 μmol·L-1 PTL group were significantly decreased(P<0.05);compared with blank control group and sh-NC group,the expression level of Piezo1 protein in the chondrocytes in sh-Piezo1 group was significantly decreased(P<0.05).Conclusion:PTL can inhibit the apoptosis of the chondrocyte induced by high-intensity cyclic mechanical stretch stress,and its mechanism may be related to inhibiting the Piezo1-mediated Ca2+influx-induced apoptosis.

Objective:To explore the risk factors for urethral stricture after transperineal anastomotic urethroplasty (TAU) by retrospectively analyzing patient data and to develop a nomogram to predict the risk of recurrence before the surgery.Methods:Clinical data of patients who underwent TAU because of post-traumatic urethral stricture from January 2016 to December 2017 in West China Hospital, Sichuan University were reviewd. A total of 78 patients were included in the retrospective analysis, with 13 of them having recurrence. The patients in the recurrence group had a median age of 49.8 and 76.9% (10/13) of them had membranous urethral stricture. The proximal urethra end was located above the superior margin of the pubic ramus (higher stricture site) in 53.8%(7/13)of patients in the recurrence group and the length of the stricture measured in the operation was (2.19±0.22) cm. In the non-recurrence group, the median age was (44.8±13.6) years old, 58.5% (38/65) of them had membranous urethral stricture, 21.5% (14/65) had higher stricture site, and the length of the stricture was (2.03±0.11) cm. Both univariate and multivariate logistics analyses were performed to evaluate the risk factors of recurrence of urethral stricture 5 years after surgery. The nomogram was built based on the multivariate logistics analysis. The Concordance Index (C-index), Receiver Operating Characteristic(ROC) curve and Calibration curve were used to evaluate the nomogram.Results:Univariate logistics analysis showed that higher stricture site, history of urethral dilation, smoking, diabetes and total serum protein may be associated with recurrence after surgery. Multivariate logistics analysis further confirmed that higher stricture site ( OR=34.64, 95% CI 3.71-754.53), history of urethral dilation( OR=13.15, 95% CI 1.27-210.00), smoking ( OR=13.75, 95% CI 2.15-166.05) and diabetes ( OR=64.98, 95% CI 3.80-1957.60) were independent risk factors for recurrent urethral stricture while higher total serum protein before surgery was related to lower recurrence risk ( OR=0.78, 95% CI 0.62-0.93). A nomogram was built based on the results. The C-index of the nomogram was 0.923(95% CI 0.908-0.938), the area under curve (AUC) was 0.923 (95% CI 0.855-0.991), and the Brier Score was 0.079. Conclusion:Higher stricture site, history of urethral dilation before surgery, smoking, diabetes and lower total serum protein before surgery are associated with higher recurrence TAU of post-traumatic urethral stricture patients. With the nomogram developed, prediction of the risk of recurrence could be achieved prior surgery.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.