Objective To explore the potential mechanism of action of paeoniflorin in diabetes mellitus,the related targets and pathways were preliminarily discussed,based on the network pharmacology and molecular docking technology.Methods Analyze the potential targets of paeoniflorin using the Swiss Target Prediction database.Genecards and OMIM databases yielded the genes of diabetes-related illnesses.After taking the intersection of the two,protein-protein interaction network(PPI)was established using STRING and Cytoscape programs to search for key genes with strong correlation and complete gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Use AutoDockTools and Pymol programs to complete protein molecule docking validation.Results The pharmacologically-related study revealed 63 targets associated with paeoniflorin,4 758 genes related to diabetes,and 50 intersection targets.15 key genes including vascular endothelial growth factor A(VEGFA),epidermal growth factor receptor(EGFR),V-Ha-ras harvey(HRAS),V-src sarcoma(SRC)and heat shock protein hs 90-alpha(HSP90AA1)were screened.RAs-associated protein 1,Ras,calcium and other signaling pathways were obtained by KEGG pathway analysis.Molecular docking results showed that paeoniflorin had good binding ability with key genes.Conclusion Paeoniflorin can treat diabetes through multiple targets and pathways,and this mechanism can provide a basis for the application of paeoniflorin in anti diabetes and drug research and development.

Objective:To evaluate the efficacy and safety of traditional Chinese medicine(TCM)in the treatment of male im-mune infertility(MII)by meta-analysis.Methods:We retrieved randomized controlled trial(RCT)on the treatment of male im-mune infertility with traditional Chinese medicine from the databases of WanFang,Chinese Biomedical Literature,Cochrane Library,Weipu,PubMed and CNKI,and performed methodological quality assessment of the RCTs identified and statistical analysis and evalua-tion of the publication bias using the RevMan5.4 software.Results:Totally,25 RCTs(2 563 cases)were included in this study.Compared with Western medicine alone in the treatment of MII,TCM achieved a significantly higher total effectiveness rate(OR=6.35,95% CI:4.96-8.13,P<0.000 01),negative conversion rate of seminal plasma anti-sperm antibodies(OR=4.52,95% CI:2.72-7.51,P<0.000 01),negative rate of serum anti-sperm antibodies(OR=2.98,95% CI:2.23-3.96,P<0.000 01),sperm concentration(MD=15.56,95% CI:11.32-19.79,P<0.000 01),grade a sperm motility(MD=3.85,95% CI:1.91-5.79,P=0.000 01),grade a+b sperm motility(MD=13.77,95% CI:7.06-20.48,P<0.000 1),sperm viability(MD=10.32,95% CI:6.78-13.86,P<0.000 01)and pregnancy rate(OR=3.53,95% CI:2.68-4.63,P<0.000 01),but a lower rate of adverse reactions(OR=0.06,95% CI:0.01-0.23,P<0.000 01).There was no statistically significant difference in the percentage of morphologically abnormal sperm between TCM and Western medicine alone in the treatment of MII(MD=-7.53,95% CI:-15.50-0.44,P=0.06).Conclusion:TCM has a definite effectiveness and high safe in the treatment of male immune infertility.

The purpose of this study was to evaluate the diagnostic performance of multiparametric ultrasound (mpUS; grayscale US, color Doppler US, strain elastography, and contrast-enhanced US) in the assessment of testicular lesions with negative tumoral markers. MpUS imaging data, patient age, serum tumor markers, scrotal pain, cryptorchidism, and related clinical information were retrospectively collected for patients who underwent mpUS examination between January 2013 and December 2019. Histologic results or follow-up examinations were used as the reference standard. In total, 83 lesions from 79 patients were included in the analysis. Fifty-six patients were finally diagnosed with benign tumors, and 23 patients were ultimately diagnosed with malignant tumors. Chi-square tests or Fisher's exact tests were used to assess the difference between the two groups. Stepwise multivariate logistic regression analysis showed that lesion diameter (odds ratio [OR] = 1.072, P = 0.005), vascularization on color Doppler US (OR = 4.066, P = 0.001), and hyperenhancement during the early phase (OR = 6.465, P = 0.047) were significant independent risk factors for malignancy; however, when compared with neoplastic lesions, pain (OR = 0.136, P < 0.001), absence of vascularization on color Doppler US (OR = 1.680, P = 0.042), and nonenhancement during the late phase (OR = 3.461, P = 0.031) were strongly associated with nonneoplastic lesions. MpUS features are useful for differentiating testicular lesions with negative tumoral markers and improving the preoperative diagnosis, which may avoid inappropriate radical orchiectomy.
Male ; Humans ; Testicular Neoplasms/pathology* ; Biomarkers, Tumor ; Retrospective Studies ; Contrast Media ; Ultrasonography/methods*

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aβ neurotoxicity and promotes Aβ clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.
Mice ; Animals ; Alzheimer Disease/pathology* ; Receptor, Nerve Growth Factor ; Amyloid beta-Peptides ; Autoantibodies ; Mice, Transgenic

Objective: To development the prognostic nomogram for malignant pleural mesothelioma (MPM). Methods: Two hundred and ten patients pathologically confirmed as MPM were enrolled in this retrospective study from 2007 to 2020 in the People's Hospital of Chuxiong Yi Autonomous Prefecture, the First and Third Affiliated Hospital of Kunming Medical University, and divided into training (n=112) and test (n=98) sets according to the admission time. The observation factors included demography, symptoms, history, clinical score and stage, blood cell and biochemistry, tumor markers, pathology and treatment. The Cox proportional risk model was used to analyze the prognostic factors of 112 patients in the training set. According to the results of multivariate Cox regression analysis, the prognostic prediction nomogram was established. C-Index and calibration curve were used to evaluate the model's discrimination and consistency in raining and test sets, respectively. Patients were stratified according to the median risk score of nomogram in the training set. Log rank test was performed to compare the survival differences between the high and low risk groups in the two sets. Results: The median overall survival (OS) of 210 MPM patients was 384 days (IQR=472 days), and the 6-month, 1-year, 2-year, and 3-year survival rates were 75.7%, 52.6%, 19.7%, and 13.0%, respectively. Cox multivariate regression analysis showed that residence (HR=2.127, 95% CI: 1.154-3.920), serum albumin (HR=1.583, 95% CI: 1.017-2.464), clinical stage (stage Ⅳ: HR=3.073, 95% CI: 1.366-6.910) and the chemotherapy (HR=0.476, 95% CI: 0.292-0.777) were independent prognostic factors for MPM patients. The C-index of the nomogram established based on the results of Cox multivariate regression analysis in the training and test sets were 0.662 and 0.613, respectively. Calibration curves for both the training and test sets showed moderate consistency between the predicted and actual survival probabilities of MPM patients at 6 months, 1 year, and 2 years. The low-risk group had better outcomes than the high-risk group in both training (P=0.001) and test (P=0.003) sets. Conclusion: The survival prediction nomogram established based on routine clinical indicators of MPM patients provides a reliable tool for prognostic prediction and risk stratification.
Humans ; Mesothelioma, Malignant ; Prognosis ; Nomograms ; Retrospective Studies ; Proportional Hazards Models

OBJECTIVE: To explore the characteristics and rules of acupoint sensitization phenomena based on knee osteoarthritis (KOA), one of the clinical dominant diseases of acupuncture-moxibustion. METHODS: In combination with literature and expert experiences, the acupoints with the highest use frequency in treatment of KOA were screened, e.g. Heding (EX-LE 2), Liangqiu (ST 34), Mingmen (GV 4), Neixiyan (EX-LE 4), Ququan (LR 8) and Dubi (ST 35). In 814 patients with KOA and 217 healthy subjects, the acupoint temperature, mechanic pain threshold and pressure pain threshold were detected separately. Using machine learning method, the sensitization was judged at each acupoint. RESULTS: Compared with healthy subjects, the acupoint temperature was increased and the mechanic pain threshold and pressure pain threshold were reduced in KOA patients (P<0.05). Besides, the cut-off value was presented to distinguish whether the acupoint was sensitized or not. The results of machine learning showed that the highest prediction accuracy of acupoint sensitization was 86.7% (Shenshu [BL 23]) and the lowest one was 73.9% (Heding [EX LE 2]). The prediction accuracy at the third clinical stage trial was higher, the highest was 93.3% (Ququan [LR 8]) in KOA patients. CONCLUSION It is confirmed that the acupoint sensitization reflects the characteristics of disease and is correlative with the conditions of illness, which may provide the reference for the auxiliary diagnosis and condition assessment of KOA.
Acupuncture Points ; Acupuncture Therapy ; Humans ; Moxibustion ; Osteoarthritis, Knee/therapy* ; Treatment Outcome

BACKGROUND: Beijing 2022 Olympic Winter Games was the second Games held amid the COVID-19 pandemic. To a certain extent, it has altered the way sporting activities operate. There is a lack of knowledge on injury risk and illness occurrence in elite winter sport athletes amid the COVID-19 pandemic. This study aimed to describe the incidence of injuries and illnesses sustained during the XXIV Olympic Winter Games in Beijing from February 4 to 20, 2022. METHODS: We recorded the daily number of injuries and illnesses among athletes reported by Beijing 2022 medical staff in the polyclinic, medical venues, and ambulance. We calculated injury and illness incidence as the number of injuries or illnesses occurring during competition or training, respectively, with incidence presented as injuries/illnesses per 100 athlete-days. RESULTS: In total, 2,897 athletes from 91 nations experienced injury or illness. Beijing 2022 medical staff reported 326 injuries and 80 illnesses, equaling 11.3 injuries and 2.8 illnesses per 100 athletes over the 17-day period. Altogether, 11％ of the athletes incurred at least one injury and nearly 3％ incurred at least one illness. The number of injured athletes was highest in the skating sports (n=104), followed by alpine skiing (n=53), ice track (n=37), freestyle skiing (n=36), and ice hockey (n=35), and was the lowest in the Nordic skiing disciplines (n=20). Of the 326 injuries, 14 (4.3％) led to an estimated absence from training or competition of more than 1 week. A total of 52 injured athletes were transferred to hospitals for further care. The number of athletes with illness (n=80) was the highest for skating (n=33) and Nordic skiing (n=22). A total of 50 illnesses (62.5％) were admitted to the department of dentistry/ophthalmology/otolaryngology, and the most common cause of illness was other causes, including preexisting illness and medicine (n=52, 65％). CONCLUSION: Overall, 11％ of athletes incurred at least one injury during the Games, which is similar to the findings during the Olympic Winter Games in 2014 and 2018. Regarding illness, 2％ of athletes were affected, which is approximately one-third of the number affected in the 2018 Olympic Winter Games.

Objective: To analyze the association between different types of obesity, BMI, and waist circumference (WC) and the risk of type 2 diabetes mellitus (T2DM) in Chinese adults. Methods: Based on the China Health and Nutrition Survey data in 2018, different types of obesity were defined across different BMI and WC combinations based on Criteria of weight for adults (WS/T 428-2013), including non-obesity, simple general obesity, simple central obesity, and complex obesity. The associations of different types of obesity, BMI, and WC with T2DM risk were explored using two-level mixed-effects logistic regression and restricted cubic spline models. Results: A total of 7 030 subjects aged 18-65 were included in this study. The prevalence of general obesity and central obesity were 16.29% (502/3 082), 42.28% (1 303/3 082) in males, and 14.41% (569/3 948), 37.87% (1 495/3 948) in females. The prevalence of complex obesity was 14.70% and 12.97% in males and females, respectively. The prevalence of T2DM was 11.28% in participants, and the prevalence in complex obesity (18.98%, 22.07%) was higher than in simple central obesity (16.24%, 15.26%) and non-obesity (9.65%, 5.18%) in males and females, respectively. Multilevel regressions showed that males with simple central obesity and complex obesity had 1.61 (95%CI: 1.24-2.08) and 2.11 (95%CI: 1.56-2.86) times the odds of T2DM, respectively, as compared with the non-obesity; and the odds of T2DM in females were 2.70 (95%CI: 1.16-6.28) times for simple general obesity, 2.62 (95%CI: 2.01-3.40) times for simple central obesity, and 4.47 (95%CI: 3.35-5.98) times for complex obesity. A nearly linear positive association was observed between BMI and T2DM risk. WC was also positively associated with T2DM risk and a non-linearly increased risk in females (P for non-linear=0.024). The risk of T2DM increased when BMI ≥22.5 kg/m² and 23.0 kg/m², WC ≥85.0 cm and 80.0 cm in males and females, respectively. Conclusions: Complex obesity adults are more likely to suffer from T2DM. The risk of T2DM increases significantly when BMI is at the normal high values and waist circumference at the stage of pre-central obesity.
Adult ; Female ; Male ; Humans ; Diabetes Mellitus, Type 2/epidemiology* ; Prevalence ; Obesity, Abdominal/epidemiology* ; Obesity/epidemiology* ; China/epidemiology*

Aim To investigate the effeet of dihydro- myricetin ( DHM ) on cognitive dysfunction in type 2 diabetes mellitus ( T2DM) rats and its mechanism.Methods SD rats were randomly divided into the normal control group ( n = 56) : normal diet and citrate buffer solution (30 mg • kg 1 ) ; T2DM model group (n =60) : high glucose, fat and low dose STZ ( 30 mg • kg 1 ) ( Four unsuccessful rats were eliminated ).Then rats in the above two groups were treated with or without DHM (250 mg • kg 1 • d intragastric).After 12 weeks, eight rats in each group were randomly selected to perform Morris water maze and Y maze test to observe the effect of DHM on cognitive function of rats.The remaining rats in each group were injected ERS antagonist tauroursodeoxycholic acid ( TUDCA ) 10 jxg • d 1 or ERS activator tunicamycin (TUN) 10 jxL, respectively.After the behavioral analysis, the hippocampal tissues of rats were taken out.The expressions of EH stress related proteins GRP78 and P- PERK were detected by Western blot.Results Both DHM and TUDCA could improve cognitive dysfunction in T2DM rats.On the contrary, TIJN reduced the effect of DHM on cognitive dysfunction in T2DM rats.TUDCA decreased the expression of GRP78 and p- PERK proteins in T2DM rats, while TUN increased the expression of GRP78 and p-PERK proteins in T2DM rats treated by DHM.Conclusion DHM improves cognitive dysfunction in T2DM rats, and the mechanism may be related to the inhibition of endoplasmic reticulum stress.

Objective: This study aimed to assess the risk of cumulative exposure to Pb, Cd, Hg, and iAs through aquatic products consumed by Chinese people. Methods: Heavy metal concentration data were obtained from the national food contamination monitoring program during 2013-2017. Consumption data were derived from the China National Food Consumption Survey in 2014 and the relative potency factor (RPF) method was used to estimate cumulative exposure for neurotoxicity and nephrotoxicity. Results: The results demonstrated that the cumulative exposure based on neurotoxicity was below the lower confidence limit on benchmark doses of lead (BMDL Conclusion The cumulative exposures of the 2-6 year-old group to the four heavy metals did not reach (but came close to) the corresponding safety threshold for both neurotoxicity and nephrotoxicity. Given that there are still other food sources of these four heavy metals, it is necessary to more closely study their cumulative health effects.
Adolescent ; Adult ; Aged ; Animals ; Arsenic/analysis* ; Child ; Child, Preschool ; Dietary Exposure/analysis* ; Environmental Monitoring ; Food Contamination/analysis* ; Humans ; Metals, Heavy/analysis* ; Middle Aged ; Risk Assessment ; Seafood/analysis* ; Water Pollutants, Chemical/analysis* ; Young Adult