italic>Schisandra chinensis is a traditional Chinese medicine with the functions of reinforcing deficiency, strengthening, and inducing astringency, appliable to treat the chronic cough and deficiency in breath, palpitation, and insomnia, etc. A hybrid mass spectrometry scanning strategy (high-definition data-independent/data-dependent acquisition, HDDIDDA), enabling the ion mobility separation and alternating data-independent acquisition/data-dependent acquisition, was established, which, in combination with in-house library-driven automatic peak annotation workflows facilitated by the UNIFI software, was utilized to systematically characterize the multi-classes of chemical components from S. chinensis. The use of an HSS T3 column (100 mm × 2.1 mm, 1.8 μm), 0.1% formic acid in H₂O-acetonitrile as the mobile phase running at the flow rate of 0.3 mL·min^-1, and column temperature at 35 ℃, could enable good separation of the S. chinensis components within 42 min. HDDIDDA scan in both the positive and negative ion modes was employed for data acquisition. Based on the automatic peak annotation, reference standards comparison, MS² data interpretation, and literature analysis, we were able to identify or tentatively characterize 105 compounds in the S. chinensis decoction, involving 56 terpenoids, 42 lignans, five glycosides, one organic acid, and one flavonoid. HDDIDDA scanning can improve the coverage of data acquisition and improve the accuracy of identification, while CCS prediction analysis provides the possibility to distinguish isomers by the ion mobility technology. The results provide reference for the intelligent material basis research of TCM.

ObjectiveTo explore the mechanism of treadmill exercise against type 2 diabetes mellitus (T2DM) with non-alcoholic fatty liver disease (NAFLD) based on the regulator effects of exercise on ferroptosis. MethodsEight 8-week-old male m/m mice were used as control group (Con, n=8), and db/db mice of the matched age were randomly divided into T2DM model group (db/db, n=8), exercise group (db+Exe, n=8), p38 mitogen-activated protein kinase (MAPK) inhibitor group (db+SB203580, n=8) and exercise combined with p38 MAPK inhibitor group (db+Exe+SB203580, n=8). After one-week adaptive feeding, the mice in the db+Exe group and db+Exe+SB203580 group underwent moderate intensity treadmill exercise for 40 min/d, 5 d/week lasting 8 weeks. The db+SB203580 group and db+Exe+SB203580 group were treated with SB203580 (a specific inhibitor of p38 MAPK) with a dose of 5 mg/kg, 5 d/week for 8 weeks. And the exercise intervention was performed 2 h later after the intraperitoneal injection of SB203580. The body weight and fasting blood glucose of mice were measured regularly every week during the experiment. After 24 h of the last intervention, the mice were weighted, the liver tissues were taken, weighted and the liver index was calculated. The pathological changes of liver were determined by Oil Red O and hematoxylin-eosin (HE) staining. The levels of blood lipids, liver function, Fe²⁺ and oxidative stress markers of liver were measured by enzyme linked immunosorbent assay (ELISA). The related mRNA expression levels of lipogenesis and inflammation were evaluated by quantitative reverse transcriptase-mediated PCR (qRT-PCR). The related protein expression levels of lipogenesis and ferroptosis in liver were determined by immunohistochemical (IHC) staining and Western blot. ResultsThe body weight, fasting blood glucose, liver index, blood lipid and transaminase levels in the db/db group were significantly increased compared with the Con group. HE and Oil Red O staining showed severe lipid accumulation and ballooning change in the liver of db/db mice. Biochemical tests showed that Fe²⁺ and MDA level of liver constitution homogenate increased, while GSH level decreased significantly. The results of qRT-PCR showed that the mRNA levels of MCP-1, IL-6, SREBF1 and ACC1 in liver tissue of db/db mice were all significantly increased. Western blot results showed that the expression levels of SREBF1, ACC1 increased, ferroptosis relative proteins were significantly decreased. The 8 weeks of exercise significantly reduced the rise in body weight, blood glucose, liver index and blood lipid levels in db/db mice. Exercise intervention also alleviated hepatic steatosis and reduced the expression levels of Fe²⁺, MDA, MCP-1, IL-6, ACC1 and SREBF1, upregulated the expression levels of GSH, NRF2, HO-1, SLC7A11 and GPX4 in liver tissue of db/db mice. The intervention of exercise combined with SB203580 significantly down-regulated the mRNA expression levels of ACC1, MCP-1, IL-6, reduced the levels of Fe²⁺ and MDA, and up-regulated the level of GSH in db/db mice. Compared with the db+Exe group, the expression of Fe²⁺, MDA, MCP-1, and SREBF1 in the liver of the db+Exe+SB203580 group mice significantly increased, while the expression level of GSH and expression levels of ferroptosis relative proteins also significantly decreased. In addition, compared with db+SB203580 group, the iron accumulation and lipid peroxidation in the liver of db+Exe+SB203580 group were significantly improved. ConclusionThe8-week treadmill exercise can effectively alleviate liver injury and steatosis, and its mechanism may be related to the inhibition of hepatocyte ferroptosis through p38 MAPK signal.

Intermittent theta burst stimulation (iTBS), a time-saving and cost-effective repetitive transcranial magnetic stimulation regime, has been shown to improve cognition in patients with Alzheimer's disease (AD). However, the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown. Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation. Here, we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1 (ISCA1, an essential regulatory factor for mitochondrial respiration) in the brain of APP/PS1 mice. In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function, which is required for ISCA1. Moreover, iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice. The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD. We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.
Humans ; Mice ; Animals ; Transcranial Magnetic Stimulation ; Alzheimer Disease/therapy* ; Cognitive Dysfunction/therapy* ; Cognition ; Sulfur ; Iron ; Iron-Sulfur Proteins ; Mitochondrial Proteins

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective To observe the clinical effect and safety of camrelizumab combined with albumin-bound paclitaxel and cisplatin in preoperative neoadjuvant chemotherapy for patients with stage Ⅲa non-small cell lung cancer(NSCLC).Methods Patients with stage Ⅲ a NSCLC were divided into the treatment group and the control group.The control group was treated with intravenous infusion of 130 mg·m-2 of paclitaxel injection on day 1 and day 8,and intravenous infusion of 75 mg·m-2 of cisplatin injection on day 1.In addition to the treatment of control group,the treatment group was treated with intravenous infusion of 200 mg of camrelizumab injection on day 1.Both groups were given 2 cycles of treatment.Clinical efficacy,tumor markers,tumor metastasis markers,T lymphocyte subsets,and safety were compared between the two groups.Results After treatment,the objective remission rate(ORR)of the treatment group and the control group was 69.64％(39 cases/56 cases)and 38.98％(23 cases/59 cases),respectively;the disease control rate(DCR)was 89.29％(50 cases/56 cases)and 72.88％(43 cases/59 cases),respectively;cytokeratin-19-fragment(Cyfra21-1)levels were(3.47±0.86)and(4.01±1.24)ng·mL-1;carcinoembryonic antigen(CEA)levels were(4.55±0.93)and(5.26±1.04)ng·mL-1;neuron-specific enolase(NSE)levels were(16.38±2.51)and(19.02±2.95)ng·mL-1;basic fibroblast growth factor(bFGF)levels were(15.82±2.34)and(18.64±2.59)μg·L-1;carbohydrate antigen 15-3(CA15-3)levels were(22.54±3.10)and(29.41±3.82)ng·mL-1;CD4+/CD8+were 1.42±0.51 and 1.30±0.32.The above indexes were significantly different between the control group and the treatment group(all P＜0.05).The adverse drug reactions in the treatment group and the control group were mainly neutropenia,thrombocytopenia,alopecia,gastrointestinal reaction and radiation pneumonia.There were no significant difference in the incidence of adverse drug reactions between the two groups(all P＞0.05).Conclusion Camrelizumab combined with albumin-bound paclitaxel and cisplatin is effective in the treatment of patients with stage Ⅲa NSCLC.

Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking. Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns. Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023-1.954;P = 0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains. Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.

Objective Hypertriglyceridemic waist(HW),hypertriglyceridemic waist-to-height ratio(HWHtR),and waist-to-hip ratio(WHR)have been shown to be indicators of cardiometabolic risk factors.However,it is not clear which indicator is more suitable for children and adolescents.We aimed to investigate the relationship between HW,HWHtR,WHR,and cardiovascular risk factors clustering to determine the best screening tools for cardiometabolic risk in children and adolescents. Methods This was a national cross-sectional study.Anthropometric and biochemical variables were assessed in approximately 70,000 participants aged 6-18 years from seven provinces in China.Demographics,physical activity,dietary intake,and family history of chronic diseases were obtained through questionnaires.ANOVA,x2 and logistic regression analysis was conducted. Results A significant sex difference was observed for HWHtR and WHR,but not for HW phenotype.The risk of cardiometabolic health risk factor clustering with HW phenotype or the HWHtR phenotype was significantly higher than that with the non-HW or non-HWHtR phenotypes among children and adolescents(HW:OR = 12.22,95%CI:9.54-15.67;HWHtR:OR = 9.70,95%CI:6.93-13.58).Compared with the HW and HWHtR phenotypes,the association between risk of cardiometabolic health risk factors(CHRF)clustering and high WHR was much weaker and not significant(WHR:OR = 1.14,95%CI:0.97-1.34). Conclusion Compared with HWHtR and WHR,the HW phenotype is a more convenient indicator with higher applicability to screen children and adolescents for cardiovascular risk factors.

Objective lo investigate the protective effect of dihydromyricetin(DHM)against exercise-induced muscle damage(EIMD)in mice and its potential mechanism. Methods Adult male C57BL/6J mice were randomly divided into control group(CG),exercise group(EG),and exercise+100 mg/kg weightd DHM(DHM)group.The intervention lasted for four weeks,during which the animals in the EG and DHM groups were subjected to exercise training for 1 h per day.The day after the training,a 90-min treadmill exercise(slope:0 and speed:18 m/min)was conducted in both EG and DHM groups.Samples of blood and gastrocnemius muscles were harvested from the three groups 24 h after the exercise,followed by the measurement of serum creatine kinase(CK)and lactate dehydrogenase(LDH)activities,total superoxide dismutase(T-SOD)activity,malondialdehyde(MDA),and skeletal muscle mitochondrial enzyme complex Ⅰ and Ⅱ activities.Histological changes in the skeletal muscle were observed by transmission electron microscopy,and the protein expressions of mitochondrial function-related pathways were detected by Western blotting. Results Skeletal muscle morphological changes and mitochondrial damage were alleviated in the DHM group compared to those in the EG.The activities of EIMD markers CK and LDH and the level of lipid peroxidation were notably repressed and the serum T-SOD activity was enhanced after DHM intervention.Western blotting demonstrated that the expressions of sirtuin type 3(SIRT3),estrogen-related receptor alpha,and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha in the skeletal muscle of mice increased after the DHM intervention. Conclusion DHM can relieve EIMD in mice,possibly by promoting the recovery of the mitochondrial structure and function in the skeletal muscle of mice after high-intensity exercise via the activation of the SIRT3 signaling pathway.

Objective:To explore the causes and therapeutic effects of pelvic pain caused by rectal fistula or bladder fistula after comprehensive treatment of cervical cancer and rectal cancer (radiotherapy, surgery, chemotherapy, and other treatments).Methods:A retrospective analysis was conducted on the clinical and pathological data of patients with pelvic tumors admitted to the First People's Hospital of Yinchuan City, Ningxia and the Affiliated Cancer Hospital of Zhengzhou University from June 2016 to June 2022. The causes of persistent pelvic pain in patients after comprehensive treatment was investigated, and the corresponding therapeutic effects after clinical treatment was observed.Results:Thirty-two tumor patients experienced persistent pain after comprehensive treatment, including 22 cases of cervical cancer and 10 cases of rectal cancer. The preoperative pain of the entire group of patients was evaluated using the digital grading method, with a pain score of (7.88±1.31) points. Among the 32 patients, there were 16 cases of rectovaginal fistula or ileovaginal fistula, 9 cases of vesicovaginal fistula, 5 cases of rectoperineal fistula, and 2 cases of vesicovaginorectal fistula. Thirty-two patients were initially treated with medication to relieve pain, and according to the ruptured organs, a fistula was made to the corresponding proximal intestinal canal and renal pelvis to intercept the intestinal contents and urine. However, the pain did not significantly be improved. The pain score of treatment with the above methods for one week was (8.13±1.13) points, and there was no statistically significant difference compared to preoperative treatment ( P=0.417). In the later stage, based on a comprehensive evaluation of whether the tumor had recurred, the value of organ preservation, the benefits of surgery, the balance between survival time and improving quality of life, pathological organ resection or repair was performed. The surgical methods included repair of leaks, local debridement combined with irrigation of proximal intestinal fluid, distal closure of the sigmoid colon combined with proximal ostomy, posterior pelvic organ resection, anterior pelvic organ resection, and total pelvic organ resection. One week after surgery, the patients' pain completely relieved or disappeared, with the pain score of (1.72±1.37) points, which was significantly divergent from the preoperative and initial surgical treatments ( P＜0.001). Conclusions:Palliative pyelostomy and proximal enterostomy cannot effectively alleviate persistent pelvic floor pain. The fundamental way to alleviate pain is complete blocking of the inflammatory erosion of the intestinal fluid and urine.

Purpose::Intramedullary nailing is the preferred internal fixation technique for the treatment of subtrochanteric fractures because of its biomechanical advantages. However, no definitive conclusion has been reached regarding whether combined cable cerclage is required during intramedullary nailing treatment. This study is performed to compare the clinical effects of intramedullary nailing with cerclage and non-cerclage wiring in the treatment of irreducible spiral subtrochanteric fractures.Methods::Patients with subtrochanteric fractures admitted to our center from January 2013 to December 2021 were retrospectively analyzed. The patients were enrolled in the case-control study according to the inclusion and exclusion criteria and divided into the non-cerclage group and the cerclage group. The patients' clinical data, including the operative time, intraoperative blood loss, hospital stay, reoperation rate, fracture union time, and Harris hip score, were compared between these 2 groups. Categorical variables were compared using Chi-square or Fisher's exact test. Continuous variables with normal distribution were presented as mean ± standard deviation and analyzed with Student's t-test. Nonnormally distributed variables were expressed as median (Q 1, Q 3) and assessed using the Mann-Whitney test. A p < 0.05 was considered significant. Results::In total, 69 patients were included in the study (35 patients in the non-cerclage group and 34 patients in the cerclage group). The baseline data of the 2 groups were comparable. There were no significant difference in the length of hospital stay (z = -0.391, p = 0.696), operative time (z = -1.289, p = 0.197), or intraoperative blood loss (z = -1.321, p = 0.186). However, compared with non-cerclage group, the fracture union time was shorter (z = -5.587, p < 0.001), the rate of nonunion was lower (χ 2= 6.030, p = 0.03), the anatomical reduction rate was higher (χ 2= 5.449, p = 0.03), and the Harris hip score was higher (z =-2.99, p = 0.003) in the cerclage group, all with statistically significant differences. Conclusions::Intramedullary nailing combined with cable cerclage wiring is a safe and reliable technique for the treatment of irreducible subtrochanteric fractures. This technique can improve the reduction effect, increase the stability of fracture fixation, shorten the fracture union time, reduce the occurrence of nonunion, and contribute to the recovery of hip joint function.