BACKGROUND:Previous studies by our research group discovered that Jiawei Xiaoyao San has a significant anti-liver cancer effect,but the specific mechanism of action was unclear. OBJECTIVE:To investigate the regulatory effects of the traditional Chinese medicine formula Jiawei Xiaoyao San on the levels of miRNAs in plasma exosomes of rats with diethylnitrosamine chronically induced primary liver cancer,based on high-throughput sequencing combined with bioinformatics. METHODS:SD rats were randomly divided into a blank control group,a liver cancer model group,and a Jiawei Xiaoyao San treatment group.Liver cancer models were induced by continuous administration of diethylnitrosamine for 12 weeks.Starting from the 17th week,rats in the Jiawei Xiaoyao San treatment group were administered Jiawei Xiaoyao San once daily until the end of the 20th week,while rats in the blank control and liver cancer model groups were given an equivalent volume of saline.Anti-hepatocellular carcinoma effects were validated by assessing the morphological structure of rat liver tissues,along with the expression of the hepatocellular carcinoma markers,Glypican-3 protein and serum alpha-fetoprotein.Plasma exosomes from each group of rats were isolated using ultracentrifugation.High-throughput sequencing technology was used to screen for differentially expressed miRNAs in rat plasma exosomes.Bioinformatics was used to predict the potential biomarkers through which Jiawei Xiaoyao San exerts its anti-liver cancer effects via liver cancer-derived exosomal miRNAs,followed by functional analysis. RESULTS AND CONCLUSION:(1)Jiawei Xiaoyao San significantly improved the morphological structure of liver tissues in a rat model of liver cancer.Compared with the liver cancer model group,the expression of liver cancer markers Glypican-3 protein and serum alpha-fetoprotein was significantly reduced in the Jiawei Xiaoyao San treatment group.(2)Bioinformatics analysis showed that in the Jiawei Xiaoyao San group,upregulated miR-223-3p in the liver cancer model group had target binding sites with genes E2F1 and NCOA1,which were closely related to liver cancer survival and prognosis.Therefore,Jiawei Xiaoyao San has a therapeutic effect on liver cancer,possibly by targeting negative regulation of NCOA1/E2F1 through liver cancer plasma-derived exosomal miR-223-3p,thereby playing anti-liver cancer effect.

Objective To observe the effects of Angelicae Sinensis Radix-Paeoniae Radix alba combined with bone marrow mesenchymal stem cells(BM-MSCs)transplantation on liver inflammation and hepatocytes regeneration in non-alcoholic steatohepatitis(NASH)associated cirrhosis;To discuss its possible mechanism.Methods West diet combined with carbon tetrachloride was used to prepare the NASH related cirrhosis model.The mice were randomly divided into control group,model group,Angelicae Sinensis Radix-Paeoniae Radix alba group,BM-MSCs group,and Angelicae Sinensis Radix-Paeoniae Radix alba+BM-MSCs group,with 12 mice in each group.After successful modeling,corresponding interventions were given according to grouping for 4 consecutive weeks.HE staining was used to observe the morphology of liver tissue;the contents of serum ALT,AST,TBil,TG,ALB,AFP,as well as the contents of IL-1β,TNF-α and HGF in liver tissue were detected;RT-qPCR was used to detect TLR9,MyD88,TRAF6 and NF-κBp65 mRNA expression in liver cells;primary liver cells were separated,CpG ODN 2216 stimulation was induced in vitro,cells supernatant was extracted,and IL-1β and TNF-α content were detected.Results Compared with the control group,inflammatory cell infiltrated in liver tissue of model group mice,accompanied by hepatocyte necrosis and collagen deposition,forming pseudo lobules;the contents of serum ALT,AST,TBil and TG increased,the content of ALB decreased,the content of HGF in liver tissue decreased,the contents of IL-1β and TNF-α increased,with statistical significance(P<0.05);the mRNA expressions of TLR9,MyD88,TRAF6 and NF-κBp65 in liver cells increased(P<0.05),and the contents of IL-1β and TNF-α in cells supernatant increased after CpG ODN 2216 induction(P<0.05).Compared with the model group,the inflammatory infiltration in liver tissue and necrosis of liver cells were reduced and the degree of liver fibrosis was alleviated in the Angelicae Sinensis Radix-Paeoniae Radix alba+BM-MSCs group,the liver tissue damage in Angelicae Sinensis Radix-Paeoniae Radix alba group and BM-MSCs group were slightly improved;except for the TG content in BM-MSCs group,all detection indicators showed significant improvement in each intervention group(P<0.05).Compared with the Angelicae Sinensis Radix-Paeoniae Radix alba group and BM-MSCs group,the Angelicae Sinensis Radix-Paeoniae Radix alba+BM-MSCs group showed statistical significance in related detection indicators(P<0.05),and demonstrated a synergistic effect.Conclusion Angelicae Sinensis Radix-Paeoniae Radix alba combined with BM-MSCs transplantation could effectively improve the liver function and promote liver cell regeneration.The mechanism is associated with the down-regulation of TLR9/NF-κB signaling pathway expressions and function,the inhibition of inflammatory cytokines secretions,and the improvement of liver inflammatory microenviroment.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To discuss the clinical value of echocardiographic indicators in assessing the short-term efficacy of transcatheter aortic valve replacement(TAVR)and surgical aortic valve replacement(SAVR)in treating patients with severe aortic valve stenosis(AS).Methods The clinical data of 70 patients with severe AS,who received treatment at the Daping Hospital of Army Military Medical University of China between June 2019 and September 2022 were retrospectively analyzed.The patients were divided into SAVR group(n=40)and TAVR group(n=30).The preoperative one-week and postoperative one-month echocardiographic indicators were compared between the two groups.Results In both groups,the postoperative one-month peak aortic valve velocity(Vmax),aortic valve mean transvalvular pressure gradient(mPG),relative thickness of chamber wall(RWT),and left ventricular mass index(LVMI)were decreased when compared with preoperative values(all P＜0.05);in TAVR group the left ventricular ejection fraction(LVEF),LVMI and incidence of perivalvular leakage were remarkably higher than those in SAVR group,while the Vmax and mPG were obviously lower than those in SAVR group(all P＜0.05).In TAVR group,the mitral regurgitation decreased from preoperative 12 patients(40％)to postoperative 2 patients(6.7％)and the over-moderate tricuspid regurgitation decreased from preoperative 7 patients(23.3％)to postoperative one patient(3.3％)(all P＜0.05).In SAVR group,the mitral regurgitation decreased from preoperative 15 patients(37.5％)to postoperative 2 patients(5.0％)and the over-moderate tricuspid regurgitation decreased from preoperative 9 patients(22.5％)to postoperative one patient(2.5％)(all P＜0.05).The pulmonary artery hypertension in TAVR group decreased from preoperative 17 patients(56.7％)to postoperative 4 patients(13.3％),which in SAVR group decreased from preoperative 22 patients(55.0％)to postoperative 5 patients(12.5％)(P＜0.05),but the differences in the above indexes between the two groups were not statistically significant(all P＞0.05).Conclusion TAVR and SAVR have similar efficacy in improving secondary valve regurgitation and pulmonary artery hypertension caused by severe AS.TAVR is superior to SAVR in improving postoperative ventricular reverse remodeling and hemodynamics,although the incidence of paravalvular leakage in TAVR is higher than that in SAVR.(J Intervent Radiol,2024,33:479-482)

Background::A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.Methods::In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.Results::From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. Conclusion::rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.Trial registration::www.ClinicalTrials.gov (No. NCT02835534).

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Objective To investigate the effects of arginine-glycine-aspartic acid(RGD)peptide hydrogels at differ-ent concentrations on the activation of Tenon capsule fibroblasts(HTF)and the expression of Yes-associated protein(YAP).Methods Three concentrations(0.5％,1.0％,2.0％)of RGD peptide hydrogels were prepared.Their internal microstructures were observed under a transmission electron microscope,and their elastic moduli(E)were measured using the rheological test.SD male rat models with conjunctival injury were established and divided into a blank group(no treatment),a low-concentration RGD group(subconjunctival injection of 0.5％RGD peptide hydrogel),a medium-con-centration RGD group(subconjunctival injection of 1.0％RGD peptide hydrogel),and a high-concentration RGD group(subconjunctival injection of 2.0％RGD peptide hydrogel).After one week,tissues were collected,and collagen fiber pro-liferation in the rat conjunctiva was observed after Masson staining.Immunohistochemistry was performed to detect the ex-pression of YAP and α-smooth muscle actin(α-SMA)in the rat conjunctiva.Scar formation cell models were constructed by stimulating HTF activation with transforming growth factor-β2(TGF-β2).According to experimental requirements,the cells were divided into a control group,a 0.5％RGD hydrogel group,a 1.0％RGD hydrogel group,a 2.0％RGD hydrogel group,and a normal group,and co-cultured for 24 hours.The relative expression levels of YAP,connective tissue growth factor(CTGF),α-SMA,fibronectin(FN),and type Ⅰ collagen(Col Ⅰ)proteins in HTF were detected by Western blot.The localization of cytoskeletal protein(F-actin)and YAP protein expression was observed under a confocal laser scanning mi-croscope.Results Electron microscopy showed that the crosslinking density of the nanofibers inside the RGD peptide hydrogel increased with the rise of the peptide concentration.Rheological measurements indicated that the E values of the 0.5％,1.0％,and 2.0％RGD peptide hydrogels were approximately 0.067 kPa,0.150 kPa,and 2.170 kPa,respectively.Masson staining results revealed that the area of collagen fiber proliferation in the conjunctiva of rats in the medium-concen-tration RGD group was significantly lower than that in the blank group(P＜0.05),while it showed no significant difference in the low-concentration and high-concentration RGD groups compared with the blank group(both P＞0.05).Immunohis-tochemistry results showed that the relative expression levels of YAP and α-SMA proteins in the conjunctiva of rats in the low-,medium-,and high-concentration RGD groups decreased compared to the blank group,and the decrease was the most significant in the medium-concentration RGD group(all P＜0.05).Cell immunofluorescence staining results indicated that the green fluorescence of F-actin was attenuated,and the red fluorescence of YAP was translocated from the nucleus to the cytoplasm in the 0.5％,1.0％,and 2.0％RGD hydrogel groups compared to the control group.Western blot results showed that the relative expression levels of YAP,CTGF,α-SMA,FN,and Col Ⅰ proteins in HTF were lower in the 0.5％,1.0％,and 2.0％RGD hydrogel groups compared to the control group,with the 1.0％RGD hydrogel group showing the most significant reduction(all P＜0.05).Conclusion With the optimal concentration of 1.0％,the RGD peptide hydro-gel can inhibit YAP protein expression and nuclear translocation and reduce HTF activation and the expression of fibrotic proteins,thus alleviating scar formation.

Objective To compare the anesthetic effects of remazolam and dexmedetomidine assisted sedation in the operation of finger replantation under ultrasound guided brachial plexus block.Methods 60 patients undergoing severed finger replantation were randomly divided into remazolam group(group R)and a dexmedetomidine group(group D)by random number table method,with 30 cases in each group.Both groups received a single brachial plexus block under ultrasound guidance.Group R was injected with remazolam 0.1 mg/kg,followed by 1 mg/(kg·h)pump until 10 min before the end of the operation.In group D,a load dose of 0.5 μg/kg of dexmedetomidine was injected,followed by continuous infusion at a rate of 0.5 μg/(kg·h)until 10 min before the end of surgery.The MAP,HR and SpO2 values of the two groups were compared when the patients entered the room(T0),the wound was cleaned and disinfected(T1);the tourniquet was upper(T2);the operation began(T3);the tourniquet was relaxed(T4);and the operation ended(T5).MOAA/S scores and BIS values were compared between the two groups at different time.The time from the beginning of medication to the absence of consciousness and the time of consciousness recovery after drug withdrawal were compared between the two groups.Blood lactic acid(Lac)before applying tourniquet and 15 min after relaxing tourniquet were compared between the two groups.The occurrence of intraoperative adverse reactions was recorded in the two groups.Results The MAP of patients in group R had little fluctuation at each time during the operation,and the MAP of patients in group D was significantly increased at T1,T2,T3 and T0 moments and at the same time as that in group R(P<0.05);HR in group R was stable at all times,and HR in group D significantly slowed down at T1,T2 and at the same time with group R(P<0.05).Patients in both groups achieved ideal sedation during the operation(MOAA/S score≤3 points),and the MOAA/S score of patients in group R at T5 minutes after drug withdrawal was higher than that at other moments of the same group and group D(P<0.05);the BIS value of group R was higher than that of group D(P<0.05).The loss time and recovery time of consciousness in group R were shorter than those in group D(P<0.05).The incidence of intraoperative hypertension and bradycardia in group D was significantly higher than that in group R,and the incidence of respiratory depression in group R was higher than that in group D(P<0.05).There was no significant change in lactate value between the two groups(P>0.05).Conclusion Remazolam and dexmedetomidine can satisfy sedation in brachial plexus nerve block for replantation of severed finger under ultrasound guidanc.Compared with dexmedetomidine,remazolam has better sedation control,stable hemodynamics,low incidence of circulatory adverse events.

Bisphenol A is a common environmental factor and endocrine disruptor that exerts a negative impact on male reproductive ability. By exploring bisphenol A-induced testicular cell death using the Institute of Cancer Research (ICR) mouse model, we found that a ferroptosis phenomenon may exist. Mice were divided into six groups and administered different doses of bisphenol A via intragastric gavage once daily for 45 consecutive days. Serum was then collected to determine the levels of superoxide dismutase and malondialdehyde. Epididymal sperm was also collected for semen analysis, and testicular tissue was collected for ferritin content determination, electron microscope observation of mitochondrial morphology, immunohistochemistry, real-time quantitative polymerase chain reaction, and western blot analysis. Exposure to bisphenol A was found to decrease sperm quality and cause oxidative damage, iron accumulation, and mitochondrial damage in the testes of mice. In addition, bisphenol A was confirmed to affect the expression of the ferroptosis-related genes, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), cyclooxygenase 2 (COX2), and acyl-CoA synthetase 4 (ACSL4) in mouse testicular tissues. Accordingly, we speculate that bisphenol A induces oxidative stress, which leads to the ferroptosis of testicular cells. Overall, the inhibition of ferroptosis may be a potential strategy to reduce male reproductive toxicity caused by bisphenol A.
Male ; Mice ; Animals ; Testis/metabolism* ; Ferroptosis ; Semen ; Oxidative Stress

Objective: To analyze the survival of newly diagnosed malignant tumors in cancer registration areas of Hubei Province from 2013 to 2015. Methods: From January 1, 2013 to December 31, 2015, all newly diagnosed malignant tumors were collected from cancer registration areas in Hubei Province, and patients were followed up using a combination of active and passive methods. Cancer survival was analyzed using the strs package in Stata software. Observed and expected survival were calculated using the life table and Ederer Ⅱ methods, and the difference in survival rate of patients with different sex, age, urban and rural areas and different cancer species was compared. Results: From 2013 to 2015, 83 987 new malignant tumors were diagnosed in cancer registration areas in Hubei Province, including 45 742 males (54.46%) and 38245 females (45.54%). The overall 5-year relative survival rate was 41.46%, 34.43% for men and 49.63% for women. With the increase of age, the observed survival rate and relative survival rate of patients of different genders showed a decreasing trend. The 5-year relative survival rate of patients with malignant tumors was 47.58% in urban areas and 26.58% in rural areas. The observed survival rate and relative survival rate in rural areas were significantly lower than those in urban areas. The overall 5-year relative survival rates for common malignancies were 20.61% for lung cancer, 15.36% for liver cancer, 22.89% for esophageal cancer, 34.92% for gastric cancer, and 54.87% for colorectal cancer. In addition, the 5-year relative survival rates of common malignant tumors in women were 78.65% for breast cancer and 52.55% for cervical cancer. Conclusions: In Hubei Province, the survival rate of malignant tumors is different among different genders, regions, age groups and cancer species. Prevention and treatment and health education should be strengthened for malignant tumor patients in rural areas and those with high incidence and low survival rate such as liver cancer and lung cancer, and relevant strategies should be formulated according to the gender and age distribution characteristics of different cancer species.
Humans ; Female ; Male ; Liver Neoplasms ; Uterine Cervical Neoplasms/epidemiology* ; Lung Neoplasms ; China/epidemiology* ; Urban Population ; Incidence ; Survival Analysis ; Rural Population ; Registries