ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

BACKGROUND:Human periodontal ligament stem cells are potential functional cells for periodontal tissue engineering.However,long-term in vitro culture may lead to reduced stemness and replicative senescence of periodontal ligament stem cells,which may impair the therapeutic effect of human periodontal ligament stem cells. OBJECTIVE:To investigate the effect of oxymatrine on the stemness maintenance and osteogenic differentiation of periodontal ligament stem cells in vitro,and to explore the potential mechanism. METHODS:Periodontal ligament stem cells were isolated from human periodontal ligament tissues by tissue explant enzyme digestion and cultured.The surface markers of mesenchymal cells were identified by flow cytometry.Periodontal ligament stem cells were incubated with 0,2.5,5,and 10 μg/mL oxymatrine.The effect of oxymatrine on the proliferation activity of periodontal ligament stem cells was detected by CCK8 assay.The appropriate drug concentration for subsequent experiments was screened.Western blot assay was used to detect the expression of stem cell non-specific proteins SOX2 and OCT4 in periodontal ligament stem cells.qRT-PCR and western blot assay were used to detect the expression levels of related osteogenic genes and proteins in periodontal ligament stem cells. RESULTS AND CONCLUSION:(1)The results of CCK8 assay showed that 2.5 μg/mL oxymatrine significantly enhanced the proliferative activity of periodontal stem cells,and the subsequent experiment selected 2.5 μg/mL oxymatrine to intervene.(2)Compared with the blank control group,the protein expression level of SOX2,a stem marker of periodontal ligament stem cells in the oxymatrine group did not change significantly(P>0.05),and the expression of OCT4 was significantly up-regulated(P<0.05).(3)Compared with the osteogenic induction group,the osteogenic genes ALP,RUNX2 mRNA expression and their osteogenic associated protein ALP protein expression of periodontal ligament stem cells were significantly down-regulated in the oxymatrine+osteogenic induction group(P<0.05).(4)The oxymatrine up-regulated the expression of stemness markers of periodontal ligament stem cells and inhibited the bone differentiation of periodontal ligament stem cells,and the results of high-throughput sequencing showed that it may be associated with WNT2,WNT16,COMP,and BMP6.

Five saponins were isolated from the kernels of Momordica cochinchinensis, by macroporous resin, silica gel, ODS column chromatography, and semi preparative HPLC. Based on MS and NMR analysis, combining with alkaline hydrolysis and acid hydrolysis, their structures were identified as: gypsogenin-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (1), quillaic acid-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (2), gypsogenin-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (3), quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (4), 18α-quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside (5). Compounds 1-5 were new compounds, and named as mubezhisides A, B, C, D, E, respectively. They all could obviously inhibited the growth of Candida albicans, C. parapsilosis, and C. tropicalis.

Objective: To explore the key factors affecting the selection and effectiveness of bladder management modalities in patients with spinal cord injury，so as to provide reference for the optimization of individualized bladder management strategies. Methods: The clinical and follow-up data of 78 patients with spinal cord injury treated in our hospital during Jan.1,2013 and Dec.31,2022 were retrospectively analyzed.The distribution of bladder management modalities among different grades of injuries was analyzed. Bowker symmetry test was used to evaluate the difference between bladder management modalities at discharge and at the end of follow-up. Multiple linear regression was used to explore the influencing factors of bladder management effects. Plotting Kaplan-Meier survival curves were adopted to calculate the median time of changes in bladder management. Results: At discharge，there were 9 cases of self-catheterization，19 cases of intermittent catheterization，22 cases of reflexive voiding，26 cases of long-term catheterization，and 2 cases using urinary collector.At the end of follow-up，there were 15 cases of self-catheterization，8 cases of intermittent catheterization，34 cases of reflexive voiding，14 cases of long-term catheterization，and 7 cases using urinary collector.There was a significant difference between the modalities of bladder management at discharge and at the end of follow-up (χ =21.43，P=0.018).Multiple linear regression showed a significant decrease of 8.60 in the total neurogenic bladder symptom score (NBSS) for grade D injuries compared with grade A injuries (P=0.026). The median time to bladder management change was 7.93 months (95%CI:5.44-9.44), with approximately 50% of patients experiencing a change in bladder management within 8 months after discharge. Conclusion: The modalities of bladder management changed significantly after discharge.The grade of injury was a key factor affecting the effectiveness of bladder management.Higher grade was associated with worse effectiveness of bladder management.

Objective: Previous observational studies have confirmed the correlation between gut microbiota and bladder cancer，but the causal relationship is still unclear.This study aimed to explore the causal relationship between them with Mendelian randomization. Methods: Genetic variation summary data of 211 gut microbiota and bladder cancer genome-wide association studies (GWAS) were obtained from the MiBioGen Consortium and Finngen database.Single nucleotide polymorphisms (SNPs) closely related to these studies were screened as instrumental variables.The causal relationship between gut microbiota and bladder cancer were analyzed with inverse variance weighting (IVW)，MR-Egger，weighted median，maximum likelihood，robust adjustment feature score and MR-PRESSO，with IVW as the primary analysis method.Additionally，sensitivity analysis was used to test the heterogeneity (Cochran Q) and horizontal pleiotropy (MR-Egger intercept term and global test from MR-PRESSO estimator) to ensure the robustness of the results. Results: The IVW results indicated that Lachnospiraceae UCG004 (OR：1.42)，Desulfovibrionales (Order) (OR：1.48)，Eubacterium ruminantium group (OR：1.33)，Olsenella (OR：1.24)，Ruminococcaceae UCG002 (OR：1.39)，Ruminococcaceae UCG005 (OR：1.42) and Ruminococcaceae UCG013 (OR：1.64) significantly increased the risk of bladder cancer.Conversely，Bacteroidetes (Phylum) (OR：0.61)，Eubacterium brachy group (OR：0.80)，Ruminococcaceae UCG004 (OR：0.73)，Rikenellaceae (Family) (OR：0.67)，Lachnospiraceae ND3007 group (OR：0.47), Adlercreutzia (OR：0.73) and an unknow genus (OR：0.75) were associated with a reduced risk of bladder cancer.Sensitivity analyses did not reveal any heterogeneity or horizontal pleiotropy. Conclusion: This study reveals the causal role of 14 gut microbiota in the pathogenesis of bladder cancer，among which Lachnospiraceae UCG004，Desulfovibrionales (Order)，Eubacterium ruminantium group，Olsenella，Ruminococcaceae UCG002，Ruminococcaceae UCG005 and Ruminococcaceae UCG013 are risk factors for bladder cancer，while Bacteroidetes (Phylum)，Eubacterium brachy group，Ruminococcaceae UCG004，Rikenellaceae (Family)，Lachnospiraceae ND3007 group，Adlercreutzia and an unknown genus are the protective factors.

Objective: To compare the effects of high intensity interval training (HIIT) exercise prescription based on machine vision and routine on HIIT the physical and mental health of female college students with simple obesity, so as to provide a basis for the development of weight loss intervention plans for this population. Methods: From August 2023 to February 2024, 115 female college students with simple obesity, selected from Lianyungang Vocational and Technical College and East China Normal University, were randomly divided into a control group ( n =57) and an observation group ( n =58) according to a random number table. The control group received routine HIIT, while the observation group received machine vision based on HIIT exercise prescription (including image acquisition module, image processing module, database management module, backend computer processing and feedback, intelligent evaluation module, which could be customized according to the subjects preferences, providing exercise prescription based on the selected training program and supervised its standardized completion of the training plan). Both were intervened for 12 weeks, 30 minutes each time, once every 2 days, and rest every Sunday. The t-test was used to compare body shape, glucose and lipid metabolism, cardiopulmonary function indicators, anxiety and depression states between two groups before and after intervention. Results: Before intervention, there were no statistically significant differences in physical and mental health status indicators between two groups of female college students ( t =0.13-0.86, all P >0.05). After intervention, body mass indexes, waist hip ratios, body fat percentage, fasting plasma glucose, 2hour postprandial plasma glucose, hemoglobin A1c, triglycerides, total cholesterol, lowdensity lipoprotein cholesterol (LDL-C), anxiety and depression scores were all reduced in both groups ( t-observation =-6.94 to -12.92, t-control =-2.71 to -10.95 ), of which the observation group [(23.46±2.18)kg/m 2, 0.70±0.06, (28.03±3.16)%, (4.55±0.67)mmol/L, (6.03±0.74)mmol/L, (5.10±0.70)%, (1.63±0.31)mmol/L, (4.24±0.58)mmol/L, (2.45±0.43)mmol/L, 35.28±4.76, and 33.03±4.03] were lower compared with the control group [(26.54±2.32)kg/m 2, 0.77±0.06, (30.74±4.38)%, (5.03±0.76)mmol/L, (6.62±0.82)mmol/L, (5.82±0.73)%, (1.98±0.35)mmol/L, (4.95±0.61)mmol/L, (2.88±0.47)mmol/L, 39.18±5.04, and 37.25±4.16] ( t =-7.34, -6.26 , -3.81, -3.59, -4.05, -5.40, -5.68, -6.40, -5.12, -4.27, -5.53)(all P <0.05). After intervention, high density lipoprotein cholesterol, stroke volume, left ventricular ejection fraction, maximum oxygen consumption, volume of tidal, and vital capacity increased in both groups ( t-observation =7.43-18.23, t-control =3.89-10.13), of which the observation group [(1.49±0.22)mmol/L, ( 72.35± 4.69)mL, (68.95±5.10)%, (36.97±3.22)mL/(kg ·( min), (25.29±4.11)mL/(kg · ( min), and (3 374.26±169.54)mL] were higher compared with the control group [(1.23±0.20)mmol/L, (67.32±4.06)mL, (64.83±5.05)%, (33.24±3.14)mL/(kg · ( min), (23.01± 3.58 )mL/(kg · ( min), and (3 197.50±125.81)mL] ( t =6.63, 6.15, 4.35, 6.29, 3.17, 6.34)(all P <0.05). Conclusion HIIT exercise prescription based on machine vision has better effects than routine HIIT on impoving the body shape, glucose and lipid metabolism, cardiopulmonary function of female college students with simple obesity, and also their mental health.

Objective To evaluate the pharmacokinetics characteristics of single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects.Methods This was a single-center,randomized,double-blind,placebo-controlled study.Twelve healthy adult Chinese subjects were randomized to receive single-dose of Etripamil nasal spray 70 mg(n=10)or placebo nasal spray(n=2).Blood and urine samples were collected prior and post dose.Etripamil in plasma and urine were analyzed by liquid chromatography-tandem mass spectrometry.The pharmacokinetic parameters were calculated by WinNonlin non-compartmental model.Results Following the single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects,the peak concentration of Etripamil in plasma was quickly attained,with a Cmax of(66.76±56.61)ng·mL-1 and a median(range)tmax of 4.00(3.00-5.00)min.The plasma concentrations of Etripamil had fallen approximately 65％from peak value at 25 min after dosing,and close to 80％within 50 min.The AUC0-last and AUC0-∞ were(3 104.16±2 654.46)and(4 048.77±2 682.38)ng·min·mL-1,respectively.The urine excretion percentage of Etripamil during 24 h was(0.01±0.01)％.Among the 12 subjects who were treated with Etripamil or placebo,10 subjects reported a total of 29 treatment-emergent adverse events(TEAEs).All of the TEAEs were mild in severity.The most common TEAEs were rhinorrhoea and lacrimation increased.Conclusion Etripamil was quickly absorbed after intranasal administration,followed by rapid distribution and elimination(not primarily excreted by renal);Etripamil 70 mg was safe and well tolerated by the healthy Chinese adult subjects.

Objective To compare endoscopic thyroidectomy via transoral submental approach with open surgery for treating thyroid tumors in terms of the clinical effectiveness.Methods We retrospectively reviewed and analyzed the clinical data and follow-up records of 154 patients in the study,who were hospitalized for thyroidectomy in our hospital from January 2021 to June 2022.Among them,74 cases undergoing endoscopic thyroidectomy via transoral submental approach were assigned to the endoscopic group and 80 cases undergoing traditional open thyroid surgery to the open surgery group.Results All operations were completed successfully and safely in both groups,with no intermediate openings in the endoscopic group.Compared with the open surgery group,the endoscopic group had significantly fewer intraoperative blood losses[(19.46±10.24)mL vs.(32.05±15.87)mL],significantly less incision length[(1.95±0.30)cm vs.(7.05±0.60)cm],significant shorter operative time[(136.66±22.44)min vs.(82.75±15.20)min],and significantly less total postoperative drainage[(111.35±38.92)mL vs.(95.45±36.73)mL](all P＜0.05).Endoscopic patients had superior postoperative pain and cosmetic satisfaction compared to open patients,and the difference was statistically significant(P＜0.05).The two groups had no significant differences in the number of lymph node dissections,parathyroid hormone,and postoperative morbidity between the two groups(P＞0.05).Conclusion The endoscopic thyroidectomy via transoral submental approach can achieve the same clinical effectiveness as the traditional open surgery.However,it is advantageous in reducing intra-operative blood loss,relieving post-operative pain,and achieving a better cosmetic effects of neck incision,thus deserving clinical promotion and application.

ObjectiveTo observe the effects of Coptidis Rhizoma-Fermentum Rubrum on non-alcoholic fatty liver disease （NAFLD） in mice and explore its possible mechanisms. MethodSixty male SPF C57BL/6J mice were randomly divided into six groups： control group， model group， low-， medium-， and high-dose Coptidis Rhizoma-Fermentum Rubrum group （0.75， 1.5， 3 g·kg^-1）， and metformin group （0.075 g·kg^-1）， with 10 mice in each group. NAFLD mouse models were induced by high-fat diet feeding for 24 weeks. The low， medium， and high-dose Coptidis Rhizoma-Fermentum Rubrum groups were administered corresponding doses of Coptidis Rhizoma-Fermentum Rubrum by gavage， while the control and model groups received an equivalent amount of saline for four weeks. Serum total cholesterol （TC）， triglycerides （TG）， free fatty acids （FFA）， and liver function markers including alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured using an automatic biochemical analyzer. Hematoxylin-eosin （HE） and oil red O staining were used to detect liver lipid deposition， and Prussian blue staining was used to measure liver ferrous ion levels. Western blot was performed to detect the expression of key proteins in the nuclear factor erythroid-2-related factor 2 （Nrf2）-glutathione peroxidase 4 （GPX4） axis. ResultAfter 24 weeks of high-fat feeding， compared with the control group， the model group showed significant increases in body weight， liver weight and liver index， and serum lipid levels （P<0.01）， as well as substantial hepatic lipid deposition with marked steatosis. Compared with the model group， Coptidis Rhizoma-Fermentum Rubrum intervention reduced body weight （P<0.01）， liver weight and liver index （P<0.01）， and serum lipid levels （P<0.05， P<0.01）， improved liver function （P<0.01）， and decreased hepatic lipid deposition， with the low-dose Coptidis Rhizoma-Fermentum Rubrum group showing the best effect. Western blot results showed that compared with those in the control group， the expression levels of Nrf2， heme oxygenase-1 （HO-1）， kelch-like ECH-associated protein 1（Keap1）， and GPX4 proteins in the model group were decreased （P<0.05， P<0.01）. Compared with the model group， Coptidis Rhizoma-Fermentum Rubrum increased the expression levels of these proteins （P<0.05， P<0.01）. ConclusionCoptidis Rhizoma-Fermentum Rubrum can alleviate fatty liver in mice， improve liver function， and reduce hepatic lipid deposition， possibly by regulating the Nrf2/GPX4 ferroptosis axis.

Objective To investigate the prevalence of thyroid nodules and its influencing factors in adult women from 2017 to 2022 in Chengdu. Methods A total of 4 612 adult female patients with thyroid nodules in the 2nd Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital from January 2017 to December 2022 were selected and included in the study group. Among the 4 027 females without thyroid nodules diagnosed by physical examination in the hospital during the same period were matched for age and included in the control group. The differences in general data and thyroid-related serological parameters between the two groups were compared and the influencing factors of thyroid nodules and the epidemiological characteristics of thyroid nodules were analyzed. Results Increased Body mass index (BMI) (OR=1.104), serum anti-thyroglobulin antibodies (TGAb) (OR=1.150) and thyroid peroxidase antibody (TPOAb) (OR=1.143) levels, diabetes mellitus (OR=1.107) and family history of thyroid disease (OR=1.271) were risk factors for thyroid nodules; high quality of life and high education level were protective factors for thyroid nodules. Physical examination screening (59.67%) was the most common way to detect thyroid nodules. Influenced by the COVID-19 epidemi, physical examination screening in the past 3 years accounted for a lower proportion of thyroid nodules found (53.18%) than the pre-epidemic level (64.10%). Conclusion Strengthening thyroid screening and popular science popularization of thyroid nodules in key target populations is the focus of thyroid nodule prevention and treatment in Chengdu in the future.