ObjectiveTo observe and compare the effects of different concentrations of cyclophosphamide (CTX) in inducing premature ovarian insufficiency (POI) model in mice and investigate the mechanism of injury. MethodsThirty-two 6~8-week-old female C57BL/6J mice were randomly divided into four groups (n=8 per group) using a weight-based block randomization method. The POI model was established via a single intraperitoneal injection of 75 mg/kg cyclophosphamide (CTX), 120 mg/kg CTX, 120 mg/kg CTX + 12 mg/kg Busulfan, or an equivalent volume of normal saline (control). Ovarian coefficients, serum estradiol (E₂) and follicle-stimulating hormone (FSH) levels were measured. Western blotting was performed to assess changes in ovarian expression levels of NAD-dependent deacetylase sirtuin-5 (SIRT5) and forkhead box O3a (FOXO3a) under different modeling conditions. After determining the optimal CTX concentration for modeling, an additional forty 6~8-week-old femal C57BL/6J mice were randomly divided into five groups (n=8 per group) using a weight-based block randomization method: saline control, 120 mg/kg CTX sampling at 1, 2, 7, or 14 days after modeling. Western blotting was used to evaluate temporal changes of ovarian SIRT5 and FOXO3a protein expression. ResultsCompared with the saline control, all concentrations of CTX (75 mg/kg CTX, 120 mg/kg CTX) and 120 mg/kg CTX + 12 mg/kg Busulfan induced POI injury in mice. The 120 mg/kg CTX group exhibited smaller changes in ovarian coefficients (P<0.001) and E₂ levels (P<0.05), whereas the 120 mg/kg CTX + 12 mg/kg Busulfan group showed rough and reduced luster fur, sluggish response and was in the worst state. Compared with the saline control group, FOXO3a expression was significantly down-regulated (P<0.05), while SIRT5 remained unchanged in the 75 mg/kg CTX group (P>0.05). In contrast, both SIRT5 (P<0.05) and FOXO3a (P<0.05) were significantly down-regulated in the 120 mg/kg CTX group. Further analysis revealed that on day 2 and 7 after 120 mg/kg CTX modeling, the expressions of SIRT5 (P<0.01) and FOXO3a (P<0.001) were significantly down-regulated, with the largest decrease observed on day 7 (SIRT5, P<0.000 1; FOXO3a, P<0.000 1). ConclusionOvarian injury in the POI model induced by 120 mg/kg CTX is milder than that in the POI model induced by 75 mg/kg CTX. Moreover, the expression changes of SIRT5 and FOXO3a are most significant on day 7 after modeling induced by 120 mg/kg CTX, which may be related to the inhibition of the SIRT5-FOXO3a signaling pathway.

Objective To systematically evaluate the predictive models for re-admission in patients with heart failure (HF) in China. Methods Studies related to the risk prediction model for HF patient re-admission published in The Cochrane Library, PubMed, EMbase, CNKI, and other databases were searched from their inception to April 30, 2024. The prediction model risk of bias assessment tool was used to assess the risk of bias and applicability of the included literature, relevant data were extracted to evaluate the model quality. Results Nineteen studies were included, involving a total of 38 predictive models for HF patient re-admission. Comorbidities such as diabetes, N-terminal pro B-type natriuretic peptide/brain natriuretic peptide, chronic renal insufficiency, left ventricular ejection fraction, New York Heart Association cardiac function classification, and medication adherence were identified as primary predictors. The area under the receiver operating characteristic curve ranged from 0.547 to 0.962. Thirteen studies conducted internal validation, one study conducted external validation, and five studies performed both internal and external validation. Seventeen studies evaluated model calibration, while five studies assessed clinical feasibility. The presentation of the models was primarily in the form of nomograms. All studies had a high overall risk of bias. Conclusion Most predictive models for HF patient re-admission in China demonstrate good discrimination and calibration. However, the overall research quality is suboptimal. There is a need to externally validate and calibrate existing models and develop more stable and clinically applicable predictive models to assess the risk of HF patient re-admission and identify relevant patients for early intervention.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

Objective To evaluate the clinical value of single-pill combination(SPC)of perindopril and amlodipine for the treatment of hypertension and provide reference for the selection and rational use in medical institutions.Methods A comprehensive clinical evaluation index system was established based on literature research and expert demonstration.Therefore,the safety,effectiveness,economy,innovation,suitability and accessibility of drugs were analyzed qualitatively and quantitatively.Results A total of 12 studies reported the outcome of perindopril and amlodipine SPC,including efficacy and safety.Perindopril amlodipine SPC was safe,and there was no significant difference in the incidence of adverse events during treatment compared with monotherapy,monotherapy combination or other antihypertensive SPC.In terms of effectiveness,perindopril and amlodipine SPC had clear antihypertensive effect,which could significantly reduce systolic blood pressure,diastolic blood pressure,pulse pressure difference and heart rate,and the blood pressure compliance rate of perindopril and amlodipine SPC was better than that of amlodipine or perindopril monotherapy group.Compared with other depressurized SPCs,it showed better or non-inferior effect.Perindopril amlodipine SPC,as a patented drug,has good innovation,high patient compliance,and has been included in China's medical insurance catalog,but the current medical institutions have a low supply rate,and drug prices and affordability are still at a relatively high level.Conclusion Perindopril amlodipine SPC has significant advantages in safety,effectiveness,suitability and innovation,but its economy and accessibility still need to be improved.

Objective:To discussed the regulation role of calcium/calmodulin dependent protein kinase(CaMK4)on γδT cells in the pathogenesis of lupus nephritis.Methods:The proportion of γδT cells in peripheral blood of LN patients and healthy con-trols were compared by flow cytometry.Magnetic bead was used to separation LN patients and healthy controls of gamma delta T cells in peripheral blood.RNA-SEQ analysis were performed in γδT cells of peripheral blood from LN patients and healthy controls.Real-time PCR and western blot were used to verify the expression level of differential gene CaMK4.The expression levels of CD80,CD86 and CD40L on γδT cells treated with CaMK4 inhibitor were detected by flow cytometry.ELISA was used to measure the level of IL-17 secreted by γδT cells after CaMK4 inhibitor treatment.Results:The proportion of γδT cells in the peripheral blood of LN patients was lower than that of healthy control group.A total of 28 differential genes related to LN were screened by RNA-SEQ sequencing,among which CaMK4 had significant by differences at molecular level and protein level.After γδT cells from LN patients were treated with CaMK4 inhibitor,KN-93,the expressions of surface costimulatory molecules CD80,CD86 and CD40L was decreased,and the level of IL-17 also was decreased.Conclusion:CaMK4 regulates γδT cells to participate in the pathogenesis of LN by IL-17 secretion and the expression of costimulatory molecules.Inhibition of CaMK4 may become a new target for the treatment of LN.

Objective To investigate the clinical efficacy and safety of endoscopic resection using snares for the treatment of gastric submucosal tumors(SMTs).Methods 66 patients diagnosed with gastric SMTs and treated with endoscopic resection from August 2017 to August 2023 were retrospectively analyzed and divided into the snare group(endoscopic resection using snares,n=33)and the traditional resection group(endoscopic resection using a traditional disposable incision knife,n=33).The operation time,overall resection rate,incidence of adverse reactions,operation cost,hospitalisation cost,and the post-operative hospital days were compared between the two groups.Results The lesion diameter was 8.00(6.00,14.00)mm in the snare group and 8.00(7.50,10.00)mm in the traditional resection group,the difference between the two groups was not statistically significant(P>0.05);The operative time in the snare group was significantly shorter than that in the traditional resection group[26.00(19.00,30.50)min vs 33.00(22.50,49.50)min],the difference was statistically significant(P<0.05);The overall resection rate in both groups was 100.0%;Neither group of patients had intraoperative perforation.There were no statistically significant differences in the incidence of adverse reactions such as intraoperative bleeding,abdominal pain and fever between the two group(P>0.05);The operative cost of the snare group was significantly lower than the traditional endoscopic resection group[(8 642.18±1 078.56)yuan vs(13 266.45±2 160.80)yuan],the difference was statistically significant(P<0.05).Conclusion Compared with traditional surgical instruments,endoscopic resection of gastric SMTs using snares has a shorter operating time,lower surgical costs,safe and effective,making it worthy of promotion.

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the main pathogen that causes COVID-19,which is fast-mutating and highly transmissible.The infection has led to a global epidemic.As the main preventive and control measure,vaccination plays a critical role in fighting a-gainst COVID-19.Although a large number of epitope-based and mucosal vaccines have been stud-ied,few peptide epitope vaccines targeting the mucosa and their functional evaluation have been re-ported.In this study,we used SARS-CoV-2 structural protein M peptide epitope predicted by the IEDB database as an antigenic target to design the MS-3S gene containing 3 050 and 1 229 signal peptides and DCpep optimized for insertion into MS2 phage coat proteins.The expression plasmid pSIP:MS-3S was constructed by cloning the PCR fragments seamlessly and was transformed into Lactiplantibacillus plantarum 18 to obtain the recombinant bacterium LP18:MS-3S.Expression conditions such as induction time,inducer concentration,rotational speed and initial pH were opti-mized.The intranasal immunization experiments were performed to examine the vaccine efficacy.The results showed that the 916 bp-long target gene MS-3S modified and optimized was amplified and used to successfully construct the recombinant bacterial strain LP18:MS-3S.The optimal con-ditions for recombinant protein expression were obtained and verified by Western blot,flow cy-tometry,immunofluorescence and other detection methods.The optimal expression conditions were determined as follows:induction time was 4 h with 100 pg/L of SppIP as the optimal induction concentration.Antibody-specific for the epitope was verified by ELISA experiments in serum,alve-olar lavage fluid and fecal dilutions of mice.In summary,a recombinant bacterial strain expressing the epitope antigen of the SARS-CoV-2 M protein peptide was constructed.The obtained protein can induce the body to produce humoral and mucosal immunity,which lays the foundation for the development of a vaccine candidate for the mucosal immunity of COVID-19.

Objectives:To establish a risk prediction model for gastrointestinal bleeding after cardiopulmonary bypass heart surgery,and to verify the prediction efficacy. Methods:A total of 1 002 patients who underwent cardiopulmonary bypass heart surgery in the department of cardiac great vascular surgery of our hospital from January 2019 to November 2023 were collected by convenient sampling method.They were divided into gastrointestinal bleeding group(n=47)and non-gastrointestinal bleeding group(n=955).Logistic regression analysis was used to establish the risk prediction model,and the area under ROC curve test and Hosmer-Lemeshow χ2 test were used to compare the two groups of data Model prediction effect.Bootstrap method was used for internal validation. Results:The risk prediction model of gastrointestinal bleeding after cardiopulmonary bypass heart surgery included four predictors:time of aortic occlusion(OR=1.021,95%CI:1.012-1.030),history of digestive disease(OR=5.710,95%CI:1.697-19.212),use of intra-aortic balloon counterpulsation(OR=22.180,95%CI:5.870-83.808),and continuous kidney replacement therapy(OR=12.159,95%CI:5.066-29.181).Model formula:Logit(P)=-5.821+0.021×time of aortic occlusion+1.742×history of digestive disease+3.099×whether intra-aortic balloon counterpulsation was used+2.498×whether continuous renal replacement therapy was used.The area under ROC curve was 0.812(95%CI:0.746-0.877),sensitivity was 64.6%,specificity was 85.7%,and Youden index was 0.503.After internal validation by Bootstrap method,the consistency index after correction is 0.813. Conclusions:The risk prediction model constructed in this study cohort has a good auxiliary prediction performance for the occurrence of gastrointestinal bleeding after cardiopulmonary bypass surgery,which is helpful for risk stratification for gastrointestinal bleeding after cardiopulmonary bypass surgery and facilitate clinical decision-making in daily clinical work.

Atherosclerosis(AS)is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease,stroke,and peripheral vascular disease.Despite the current treatments,mortality and disability still remain high.Sonodynamic therapy(SDT),a non-invasive and localized methodology,has been developed as a promising new treatment for inhibiting atherosclerotic progression and sta-bilizing plaques.Promising progress has been made through cell and animal assays,as well as clinical trials.For example,the effect of SDT on apoptosis and autophagy of cells in AS,especially macrophages,and the concept of non-lethal SDT has also been proposed.In this review,we summarize the ultrasonic parameters and known sonosensitizers utilized in SDT for AS;we elaborate on SDTs therapeutic effects and mechanisms in terms of macrophages,T lymphocytes,neovascularization,smooth muscle cells,lipid,extracellular matrix and efferocytosis within plaques;additionally,we discuss the safety of SDT.A comprehensive summary of the confirmed effects of SDT on AS is conducted to establish a framework for future researchers.