This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Plant Leaves/chemistry*

Extensive studies have identified potential adverse effects on semen quality of obesity, based on body mass index, but the association between body fat distribution, a more relevant indicator for obesity, and semen quality remains less clear. We conducted a longitudinal study of 4304 sperm donors from the Guangdong Provincial Human Sperm Bank (Guangzhou, China) during 2017-2021. A body composition analyzer was used to measure total and local body fat percentage for each participant. Generalized estimating equations were employed to assess the association between body fat percentage and sperm count, motility, and morphology. We estimated that each 10% increase in total body fat percentage (estimated change [95% confidence interval, 95% CI]) was significantly associated with a 0.18 × 10 6 (0.09 × 10 6 -0.27 × 10 6 ) ml and 12.21 × 10 6 (4.52 × 10 6 -19.91 × 10 6 ) reduction in semen volume and total sperm count, respectively. Categorical analyses and exposure-response curves showed that the association of body fat distribution with semen volume and total sperm count was stronger at higher body fat percentages. In addition, the association still held among normal weight and overweight participants. We observed similar associations for upper limb, trunk, and lower limb body fact distributions. In conclusion, we found that a higher body fat distribution was significantly associated with lower semen quality (especially semen volume) even in men with a normal weight. These findings provide useful clues in exploring body fat as a risk factor for semen quality decline and add to evidence for improving semen quality for those who are expected to conceive.
Humans ; Male ; Adult ; Semen Analysis ; China ; Body Fat Distribution ; Longitudinal Studies ; Sperm Count ; Sperm Motility ; Body Mass Index ; Tissue Donors ; Obesity/complications* ; Spermatozoa ; Young Adult ; Middle Aged ; East Asian People

BACKGROUND: Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction. OBJECTIVE: This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale. METHODS: This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment. DISCUSSION This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).
Humans ; ST Elevation Myocardial Infarction/therapy* ; Stroke Volume ; Ventricular Remodeling ; Prospective Studies ; Microcirculation ; Ventricular Function, Left ; Myocardial Infarction/etiology* ; Treatment Outcome ; Percutaneous Coronary Intervention/adverse effects* ; Heart Failure/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic

This study aimed to investigate the anti-inflammatory effect of astragaloside Ⅳ in mice with ulcerative colitis(UC) and its effect on the percentage of peripheral blood T helper(Th17) cells. Following the establishment of UC mouse model with 2% sodium dextran sulfate(DSS), mice in the positive control group and low-and high-dose astragaloside Ⅳ groups were treated with corresponding drugs by gavage. Disease activity index(DAI) was calculated, and serum interleukin-17(IL-17), tumor necrosis factor-α(TNF-α), and transforming growth factor-β(TGF-β) levels were assayed by ELISA. The pathological changes in colon tissue were observed by HE staining, and Th17/regulatory T cells(Treg) ratio in the peripheral blood was determined by flow cytometry. Western blot was conducted for detecting the relative protein expression levels of forkhead box protein P3(Foxp3) and retinoic acid-related orphan nuclear receptor γT(ROR-γt). The findings demonstrated that in normal mice, the colonic structure was intact. The goblet cells were not reduced and the glands were neatly arranged, with no mucosal erosion, bleeding, or positive cell infiltration. In the model group, the colonic mucosal structure was seriously damaged, manifested as disordered arrangement or missing of glands, vascular dilatation, congestion, and massive inflammatory cell infiltration. The pathological injury of colon tissue was alleviated to varying degrees in drug treatment groups. Compared with the normal group, the model group exhibited elevated percentage of Th17 cells, increased IL-17 and TNF-α content, up-regulated relative ROR-γt protein expression, lowered TGF-β, reduced percentage of Treg cells, and down-regulated relative Foxp3 protein expression. The comparison with the model group showed that DAI score, pathological score, percentage of Th17 cells, IL-17 and TNF-α content, and relative ROR-γt protein expression in the positive control group, low-dose astragaloside Ⅳ group, and high-dose astragaloside Ⅳ group were decreased, while TGF-β content, percentage of Treg cells, and relative Foxp3 protein expression were increased. The DAI score, pathological score, percentage of Th17 cells, IL-17 and TNF-α content, and relative ROR-γt protein expression in the low-dose astragaloside Ⅳ group were higher than those in the positive control group, whereas the content of TGF-β, percentage of Treg cells, and relative Foxp3 protein expression were lower. DAI score, pathological score, percentage of Th17 cells, IL-17 and TNF-α content, relative ROR-γt protein expression in the high-dose astragaloside Ⅳ group declined in contrast to those in the low-dose astragaloside Ⅳ group, while the TGF-β content, percentage of Treg cells, and relative Foxp3 protein expression rose. There was no significant difference between the positive control group and the high-dose astragaloside Ⅳ group. Astragaloside Ⅳ is able to inhibit inflammatory response and diminish the percentage of Th17 cells in mice with UC.
Animals ; Colitis, Ulcerative/metabolism* ; Mice ; Saponins/pharmacology* ; T-Lymphocytes, Regulatory ; Th17 Cells ; Triterpenes/pharmacology*

The vagina contains at least a billion microbial cells,dominated by lactobacilli.Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age,as well as cervical,fecal,and salivary samples from a second cohort of 632 women.Factors such as pregnancy history,delivery history,cesarean section,and breastfeeding were all more important than menstrual cycle in shaping the microbiome,and such information would be necessary before trying to interpret differences between vagino-cervical micro-biome data.Greater proportion of Bifidobacterium breve was seen with older age at sexual debut.The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history.Potential markers for lack of menstrual regularity,heavy flow,dysmenor-rhea,and contraceptives were also identified.Lactobacilli were rare during breastfeeding or post-menopause.Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome.Gut and salivary microbiomes,plasma vitamins,metals,amino acids,and hormones showed associations with the vagino-cervical microbiome.Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.

Objective To determine the current disinfection quality and understand existing problems in clinical institutions in Yangpu District， and provide scientific evidence for improving hospital infection control. Methods From 2018 to 2020， the specimens were collected from medical instruments， disinfectant in use， dialysis water in hemodialysis rooms， air， surface of objects， sterilization equipment， hands of medical staff， dental therapy water and sewage in clinical institutions in Yangpu District， and then examined for disinfection quality. Results A total of 1 420 samples were collected consecutively in 3 years， in which the total qualified rate was determined to be 88.52%. The qualified rates in secondary and tertiary hospitals， primary health centers， and private clinics were 94.86%， 90.22% and 75.74%， respectively， with a significant difference （χ²=95.01， P<0.01）. The qualified rates in sterilization equipment， air， and dialysis water were all 100.00%； in contrast， the rates in medical instruments， surface of objects， hands of medical staff， disinfectants in use， dental therapy water， and sewage were 98.28%， 97.63%， 95.05%， 93.39%， 54.71% and 50.00%， respectively. Conclusion Overall disinfection quality remains good in clinical institutions in Yangpu District of Shanghai， whereas the quality in private clinics is low. In addition， dental therapy water and hospital sewage might be susceptible to contamination， which warrants further improvement in the disinfection and monitoring.

Tumors are new organisms formed by uncontrollable cell proliferation of local tissues driven by various oncogenic factors. The cause of tumors is unknown with life-threating outcome. Tumors can be classified into benign tumors， borderline tumors， and malignant tumors according to their pathological properties. Among them， malignant tumor is commonly known as cancer， with no specific medicines or reliable cure means， so this is a hot spot and difficult point in current medical research. In ancient literatures， there are many records about the efficacy of Chinese herbal medicine in treating tumor， and modern pharmacological researches have shown that more and more active ingredients of traditional Chinese medicine（TCM） have gradually highlighted their inhibitory effect on various types of tumor. Caulis sinomenii has been used for treatment of rheumatic diseases in TCM for a long history. Sinomenine is a major bioactive alkaloid presented in C. sinomenii， which has demonstrated a wide range of pharmacological activities such as anti-inflammation， immunosuppression， analgesia and sedation， and due to its slightly soluble in water， it is commonly used in clinic in the form of hydrochloride， with its commercial name of Zhengqing Fengtongning. Recent studies show that sinomenine alone or combined with chemoradiotherapy can inhibit growth of several tumors significantly or in a synergistic way， so it is termed as an inhibitor of tumors. Anti-tumor effect of sinomenine involve inhibition of tumor cell proliferation， induction of tumor cell apoptosis， blockade of tumor cell cycle， suppression of tumor invasion and metastasis， induction of autophagy of tumor cells， and reversal of multidrug resistance of tumor cells. Upon combination with nanomaterials， it can enhance efficiency and reduce toxicity. Here we summarized and reviewed recent advances on basic anti-tumor research of sinomenine， and then made a classification and description according to its in vivo and in vitro pharmacological action and mechanism of action， so as to elucidate the great potential of sinomenine as a promising anti-tumor drug， and provide reference for further research on its anti-tumor mechanism.

Objective: To observe the short and long term effect of addition and subtraction therapy of Shentong Zhuyutang to myofascial pain syndrome (MPS) with stagnation of blood stasis and to investigate its mechanism of action.Method: One hundred and forty-eight eligible patients were randomly divided into control group (73 cases) and observation group (75 cases) by random number table.Patients in both groups got electroacupuncture treatment.Patients in control group additionally got Yaotong capsules,4 grains/time,3 times/day.Patients in observation group additionally got addition and subtraction therapy of Shentong Zhuyutang,1 dose/day.The treatment was continued for 6 weeks in both groups,and 16 weeks follow-up was recorded.Before treatment,and at the 1^st,2^nd,3^rd,4^th,5^th,6^th week after treatment,scores of visual analogue scale (VAS) was graded.Before and after treatment,scores of JOA,Roland-Morris disability questionnaire (RDQ),body damage index assessment scale (PⅡ scale),stagnation of blood stasis,and Pittsburgh sleep quality index (PSQI) were graded.Levels of thromboxane 2(TXB₂),6-ketone-prostaglandin F_1α(6-keto-PGF_1α) were detected,and TXB₂/6-keto-PGF_1α was calculated;in addition,the recurrence was recorded and followed up.Result: By rank sum test,the clinical efficacy in observation group was better than that in control group (Z=1.969,P<0.01).Analysis of variance of repeated measures indicated that,scores of VAS were decreased gradually at the 1^st,2^nd,3^rd,4^th,5^th,6^th week in both groups after treatment (F_control=5.801,F_observation=6.649,P<0.05).Paired t-test indicated that scores of VAS in observation group were lower than those in control group at 2^nd,3^rd,4^th,5^th,6^th week (P<0.01).Scores of three dimensions of JOA scale and total score in observation group were higher than those in control group (P<0.01).Scores of RDQ,PⅡ,PSQI,stagnation of blood stasis,whole blood viscosity (high cut and low cut),plasma viscosity,fibrinogen,TXB₂,and T/K in observation group were lower than those in control group (P<0.01),and level of 6-keto-PGF_1α was higher than that in control group (P<0.01).In addition,the recurrence rate in observation group was 12%,lower than 26.03% in control group (χ²=4.745,P<0.05).Conclusion: Based on acupuncture treatment,addition and subtraction therapy of Shentong Zhuyutang can relieve the pain caused by myofascial pain syndrome (MPS) with stagnation of blood stasis,recover lumbar activity function,reduce rate of recurrence,and ameliorate blood circulation,with anti-inflammatory and analgesia effects.

OBJECTIVE: To observe the difference in the therapeutic effects on rheumatoid arthritis (RA) between the combined -deep needling and bloodletting technique and the regular needling technique. METHODS: A total of 70 patients were randomized into an observation group (35 cases) and a control group (35 cases, 4 cases dropped-out). Dazhui (GV 14), Shenzhu (GV 12), Zhiyang (GV 9), Jinsuo (GV 8), Ganshu (BL 18), Shenshu (BL 23), Zhibian (BL 54), Weizhong (BL 40), Taixi (KI 3) and Tianzong (SI 11), etc. were selected in the two groups. Additionally, in the observation group the -deep needling technique was adopted at Tianzong (SI 11) and Zhibian (BL 54), the bloodletting technique at the local swollen area and the even-needling technique at the rest acupoints. In the control group, the even-needling technique was applied to all of the acupoints. Acupuncture treatment was given once every two days, 3 times a week and for 12 weeks totally. The numbers of tender points at the knee joint, the numbers of swollen sites at the knee joint, the visual analogue scale (VAS) score and the American health assessment questionnaire (HAQ) score were observed in the two groups before and after treatment, as well as the changes in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The American College of Rheumatology (ACR) criteria was adopted to evaluate the therapeutic effects of the two groups. RESULTS: After treatment, the numbers of tender points, the numbers of swollen sites, VAS score and HAQ score were all improved as compared with those before treatment in the two groups (all <0.01), and the results in the observation group were better than those in the control group (all <0.05). After treatment, ESR and CRP levels were all reduced as compared with those before treatment in the two groups (all <0.01), but there was no significant differences between the two groups (both >0.05). The standard-reaching rates of ACR 20 and ACR 50 in the observation group were 94.3% (33/35) and 31.4% (11/35) respectively, which were better than 67.7% (21/31) and 6.5% (2/31) in the control group (<0.01, <0.05). CONCLUSION The acupuncture with the -deep and bloodletting techniques and the acupuncture with regular needling technique are all effective on RA. The therapeutic effects of the acupuncture treatment with the -deep and bloodletting techniques are better than that with regular needling technique.
Acupuncture Points ; Acupuncture Therapy ; Arthritis, Rheumatoid ; therapy ; Bloodletting ; Humans ; Treatment Outcome

BACKGROUNDMitofusin-2 (MFN2), a well-known mitochondrial fusion protein, has been shown to participate in innate immunity, but its role in mediating adaptive immunity remains poorly characterized. In this study, we explored the potential role of MFN2 in mediating the immune function of T lymphocytes.

METHODSWe manipulated MFN2 gene expression in Jurkat cells via lentiviral transduction of MFN2 small interfering RNA (siRNA) or full-length MFN2. After transduction, the immune response and its underlying mechanism were determined in Jurkat cells. One-way analysis of variance and Student's t-test were performed to determine the statistical significance between the groups.

RESULTSOverexpression of MFN2 enhanced the immune response of T lymphocytes by upregulating Ca2+ (359.280 ± 10.130 vs. 266.940 ± 10.170, P = 0.000), calcineurin (0.513 ± 0.014 vs. 0.403 ± 0.020 nmol/L, P = 0.024), and nuclear factor of activated T cells (NFATs) activation (1.040 ± 0.086 vs. 0.700 ± 0.115, P = 0.005), whereas depletion of MFN2 impaired the immune function of T lymphocytes by downregulating Ca2+ (141.140 ± 14.670 vs. 267.060 ± 9.230, P = 0.000), calcineurin (0.054 ± 0.030 nmol/L vs. 0.404 ± 0.063 nmol/L, P = 0.000), and NFAT activation (0.500 ± 0.025 vs. 0.720 ± 0.061, P = 0.012). Furthermore, upregulated calcineurin partially reversed the negative effects of MFN2 siRNA on T cell-mediated immunity evidenced by elevations in T cell proliferation (1.120 ± 0.048 vs. 0.580 ± 0.078, P = 0.040), interleukin-2 (IL-2) production (473.300 ± 24.100 vs. 175.330 ± 12.900 pg/ml, P = 0.000), and the interferon-γ/IL-4 ratio (3.080 ± 0.156 vs. 0.953 ± 0.093, P = 0.000). Meanwhile, calcineurin activity inhibitor depleted the positive effects of overexpressed MFN2 on T cells function.

CONCLUSIONSOur findings suggest that MFN2 may regulate T cell immune functions primarily through the Ca2+-calcineurin-NFAT pathway. MFN2 may represent a potential therapeutic target for T cell immune dysfunction-related diseases.