OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

Intervertebral disc degeneration (IDD) is largely attributed to impaired endogenous repair. Nucleus pulposus-derived stem cells (NPSCs) senescence leads to endogenous repair failure. Small extracellular vesicles/exosomes derived from mesenchymal stem cells (mExo) have shown great therapeutic potential in IDD, while whether mExo could alleviate NPSCs senescence and its mechanisms remained unknown. We established a compression-induced NPSCs senescence model and rat IDD models to evaluate the therapeutic efficiency of mExo and investigate the mechanisms. We found that mExo significantly alleviated NPSCs senescence and promoted disc regeneration while knocking down thioredoxin (TXN) impaired the protective effects of mExo. TXN was bound to various endosomal sorting complex required for transport (ESCRT) proteins. Autocrine motility factor receptor (AMFR) mediated TXN K63 ubiquitination to promote the binding of TXN on ESCRT proteins and sorting of TXN into mExo. Knocking down exosomal TXN inhibited the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2) and activator protein 1 (AP-1). NRF2 and AP-1 inhibition reduced endogenous TXN production that was promoted by exosomal TXN. Inhibition of NRF2 in vivo diminished the anti-senescence and regenerative effects of mExo. Conclusively, AMFR-mediated TXN ubiquitination promoted the sorting of TXN into mExo, allowing exosomal TXN to promote endogenous TXN production in NPSCs via TXN/NRF2/AP-1 feed-forward circuit to alleviate NPSCs senescence and disc degeneration.

ObjectiveTo analyze the community structure and dynamics of parasitic fleas on the body surface of host animals and nested fleas in different seasons in the natural foci of wild rat plague in Yulong County，Yunnan Province， to explore the relationship between seasonal fluctuation of fleas and the prevalence of plague among animals， so as to provide evidence for plague prevention and control in the natural foci. MethodsNanxi Village， Huangshan Town， the core area of plague epidemic in Yulong County， was selected as the monitoring sample area in December 2019 （winter）， August 2020（summer）， October 2020（autumn） and March 2021（spring）. Host animals were captured by rattrap at night and rat nests were excavated for collecting parasitic fleas on host animals and rat nest fleas in different seasons. Excel 2010 and SPSS 26.0 software were used to analyze the data， and Chi square test was used to compare the rate. Community ecological indicators were used to analyze the community structure and species diversity of the host animals and their parasitic fleas. ResultsA total of 355 vector fleas were captured， belonging to 7 species of 5 genera in 2 families. 441 small animals were captured and 138 rat body fleas were detected with the flea infection rate of 14.51% and the flea index 0.31. 96 effective rat holes were excavated and 217 fleas were detected with the flea infection rate of 35.42% and the flea index 2.26. Among the four seasons， the flea infection rates of rat body and rat nests were higher in summer and winter， showing a significant difference in general （χ²=15.851， P<0.01； χ²=16.398， P<0.01）. The dominant species of flea community were Ctenophthalmus quadratus， Stenischia humilis， Neopsylla specialis and Frontopsylla spadix， with a dominance index of 0.434， 0.254， 0.180 and 0.110， respectively. The diversity and evenness of rat body fleas showed a distribution characteristic of decreasing， increasing and then decreasing again with season changes， and both were the highest in spring， while the ecological dominance showed an opposite trend. The diversity and evenness of rat nest fleas showed a distribution characteristic of increasing first and then decreasing in summer， autumn and winter， with the highest in autumn， while the ecological dominance was diametrically opposite. ConclusionThe fleas community structure is relatively stable in Yulong County， but the number of species in the community is unevenly distributed by seasons， and the status of dominant species is prominent. Local authorities should carry out timely preventive deratization and depulization measures according to the results of daily monitoring， so as to effectively avoid the prevalence and spread of plague among animals in plague foci.

Child ; Humans ; East Asian People ; Quality of Life ; Students ; Child Abuse, Sexual ; Young Adult ; Resilience, Psychological

To explore the feasibility of applying magnetic stimulation technology to the movement control of animal robots, the influence of coil radius, number of turns and other factors on the intensity, depth and focus of magnetic stimulation was simulated and analyzed for robot pigeons. The coil design scheme was proposed. The coil was placed on the head and one of the legs of the pigeon, and the leg electromyography (EMG) was recorded when magnetic stimulation was performed. Results showed that the EMG was significantly strengthened during magnetic stimulation. With the reduction of the output frequency of the magnetic stimulation system, the output current was increased and the EMG was enhanced accordingly. Compared with the brain magnetic stimulation, sciatic nerve stimulation produced a more significant EMG enhancement response. This indicated that the magnetic stimulation system could effectively modulate the functions of brain and peripheral nerves by driving the coil. This study provides theoretical and experimental guidance for the subsequent optimization and improvement of practical coils, and lays a preliminary theoretical and experimental foundation for the implementation of magnetic stimulation motion control of animal robots.
Animals ; Columbidae ; Robotics ; Motion ; Brain ; Magnetic Phenomena

OBJECTIVE: To explore the effect of WDSUB1 on dextran sulfate sodium (DSS)-induced inflammatory colon injury in mice and the underlying mechanism. METHODS: Different WDSUB1 siRNA sequences were transfected into mouse fibroblast L929 cells and the optimal sequence was selected by Western blotting. Twelve male C57BL/6 mice were randomized into two groups for injection of siWDSUB1 or siControl via the caudal vein, followed by treatment with 2.5% DSS in drinking water to establish mouse models of DSS- induced colitis (n=6). The expression level of WDSUB1 in the colon tissue of the mice was detected with Western blotting and RT-PCR, the changes in body weight and fecal condition were recorded, and the clinical symptoms of the mice were evaluated. The mRNA expression levels of IL-6, COX-2 and TNF-α and the protein expression of IκBα and P65 in the colon tissues were detected with RT- PCR and Western blotting, respectively. RESULTS: The mRNA and protein expressions of WDSUB1 in the colon tissues were significantly lower in colitis mice with WDSUB1 knock-down than in the control mice. Compared with the control mice, the mice receiving siWDSUB1 injection showed obviously milder weight loss, diarrhea and hematochezia with significantly lower mRNA expressions of COX2, IL-6 and TNFα (P < 0.05) and protein expression of IκBα but without obvious changes in P65 expression in the colon tissue. CONCLUSION WDSUB1 knockdown can alleviate DSS- induced colitis in mice possibly by inhibiting the NF-κB signaling pathway and decreasing the expression of inflammatory factors in the colon tissues.
Animals ; Colitis/chemically induced* ; Cyclooxygenase 2/metabolism* ; Dextran Sulfate/adverse effects* ; Interleukin-6/pharmacology* ; Male ; Mice ; Mice, Inbred C57BL ; NF-KappaB Inhibitor alpha/metabolism* ; NF-kappa B/metabolism* ; RNA, Messenger ; Signal Transduction ; Tumor Necrosis Factor-alpha/metabolism*

The incidence of infertility has recently risen. Semen quality is an important male fertility indicator, and dietary factors can affect semen quality. We conducted this systematic review and meta-analysis to determine the effects of healthy dietary patterns on semen quality. A literature search was conducted in 3 databases (Embase, Web of Science and PubMed) on August 21, 2021. The included cross-sectional studies examined the influence of the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and prudent diet patterns on semen quality parameters; six studies (1244 subjects) were included. By comparing high consumption with low consumption of healthy dietary patterns, the results of the meta-analysis showed significantly higher sperm concentrations (mean difference [MD] = 6.88 × 10⁶ ml^-1, 95% confidence interval [CI]: 1.26 × 10⁶ ml^-1-12.49 × 10⁶ ml^-1; P < 0.05), a significant increase in total sperm count (MD = 16.70 × 10⁶, 95% CI: 2.37 × 10⁶-31.03 × 10⁶; P < 0.05), and a significant increase in progressive sperm motility (MD = 5.85%, 95% CI: 2.59%-9.12%; P < 0.01). The sperm concentration, progressive sperm motility, and total sperm count were significantly higher in men with higher versus lower consumption of healthy dietary patterns. However, the results must be interpreted with caution.
Cross-Sectional Studies ; Humans ; Infertility, Male ; Male ; Semen ; Semen Analysis ; Sperm Count ; Sperm Motility ; Spermatozoa

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

OBJECTIVES: To explore the influencing factors of the horizontal distance of bodies in the high falling scene and the feasibility of inferring the falling mode based on it. METHODS: A total of 614 high falling deaths and 15 cases of corpse dumping from high altitudes were collected. The relationship between the horizontal distance and the falling height, as well as the sex, age and manner of death (suicide, accident and corpse dumping) were observed. RESULTS: The horizontal distance increased with the increase of falling height, and the difference among the height groups was statistically significant. The horizontal distance decreased with the increase of the age of the deceased, in each height group, the difference between the group over 60 years old and other age groups was statistically significant (P<0.05). The horizontal distance of male deceased was (1.99±0.27) m, which was greater than that of female deceased (1.88±0.19) m, and the difference was statistically significant in partial height groups (P<0.05). Roof falls had a greater horizontal movement distance than window falls. Except for the >20-30 m group, there was no significant difference in horizontal distance between suicide high falls and accidental high falls in other height groups. CONCLUSIONS The horizontal distance is affected by the falling height, the sex and age of the victim, and the spatial characteristics of the falling starting point.
Body Height ; Cadaver ; Female ; Homicide ; Humans ; Male ; Middle Aged ; Suicide

OBJECTIVE：To study the effects of shikonin on autophagy and apoptosis of human colon cancer HCT 116 cells. METHODS：After treating HCT 116 cells for 48 h with shikonin at 0（blank control ）10，20，40 μg/mL，MTT method was used to detect inhibitory rate of cell proliferation. Flow cytometry was used to detect cell apoptosis rate. RT-qPCR assay and Western blotting were respectively used to detect mRNA and protein expressions of microtubule associated protein light chain 3（LC3）and autophagy-related protein Beclin- 1 and p 62. RESULTS ：Compared with blank control ，after treated with 10，20，40 μ g/mL shikonin for 48 h，proliferation inhibitory rate and apoptosis rate of HCT 116 cells were increased significantly （P＜0.05 or P＜ 0.01）. After treated with 10，20，40 μg/mL shikonin for 48 h，mRNA and protein expressions of LC 3，Beclin-1 and p 62 in HCT116 cells were increased to different extents ；except that mRNA expression of LC 3 was not increased significantly after treated with 10 μg/mL shikonin，the difference were statistically significant in other indexes ，compared with blank control （P＜0.05 or P＜0.01）. CONCLUSIONS ：Shikonin can induce the apoptosis of human colon cancer HCT 116 cells and activate its autophagy pathway.