OBJECTIVES: To explore the potential of pyrroline-5-carboxylate reductase 1 (PYCR1) as a pan-cancer biomarker and investigate its expression, function, and clinical significance in bladder cancer (BLCA). METHODS: Bioinformatics analysis was conducted to evaluate the associations of PYCR1 with prognosis, immune microenvironment remodeling, tumor mutation burden (TMB), and microsatellite instability (MSI) in cancer patients. Using the TCGA-BLCA dataset, univariate and multivariate regression analyses were performed to assess the potential of PYCR1 as an independent prognostic risk factor for BLCA, and a clinical decision model was constructed. The IMvigor210 cohort was utilized to evaluate the potential of PYCR1 for independently predicting the efficacy of immunotherapy. The pRRophetic was employed to screen candidate chemotherapeutic agents for treating BLCA with high PYCR1 expression. The CMap-XSum algorithm and molecular docking techniques were used to explore and validate small molecule inhibitors of PYCR1. RESULTS: A high expression of PYCR1 was significantly associated with poor prognosis, immune cell infiltration, TMB and MSI in various tumors (r>0.3). PYCR1 was overexpressed in BLCA, and high PYCR1 expression was closely related to poor prognosis in BLCA patients (HR: 1.14, 95% CI: 1.02-1.68, P=0.006). The IC₅₀ of the anti-cancer drugs cetuximab, 5-fluorouracil, and doxorubicin increased significantly in BLCA cell lines with high PYCR1 expressions (P<0.0001). CONCLUSIONS High PYCR1 expression is an independent risk factor for poor prognosis in BLCA patients and can serve as a significant indicator for clinical decision-making as well as a marker for predicting sensitivity to chemotherapeutic agents and the efficacy of immunotherapy.
Humans ; Urinary Bladder Neoplasms/genetics* ; Immunotherapy ; Prognosis ; Pyrroline Carboxylate Reductases/metabolism* ; Biomarkers, Tumor/genetics* ; delta-1-Pyrroline-5-Carboxylate Reductase ; Microsatellite Instability ; Tumor Microenvironment ; Mutation ; Computational Biology ; Molecular Docking Simulation

Bacillus is a class of spore-producing Gram-positive bacteria that produce a variety of antimicrobial substances with different structures and functions. The application of the antimicrobial substances produced by Bacillus can effectively inhibit the activity of harmful bacteria and fungi and promote the sustainable development of green agriculture. The antimicrobial substances produced by Bacillus mainly include proteins, lipopeptides, polyketones, and polypeptides. This paper reviews the synthesis gene clusters, synthesis pathways, structures, and mechanisms of various antimicrobial substances produced by Bacillus and discusses the challenges in the industrial application of these antimicrobial substances. Furthermore, this paper clarifies the future research and development focuses and prospects the application prospects, and provides comprehensive theoretical support for the in-depth research and wide application of the antimicrobial substances produced by Bacillus.
Bacillus/genetics* ; Anti-Infective Agents/metabolism* ; Bacterial Proteins/genetics* ; Antimicrobial Peptides/biosynthesis* ; Lipopeptides/biosynthesis*

Objective To make the cost-effectiveness analysis of pembrolizumab and platinum chemotherapy as the first-line treatment for advanced non-small cell lung cancer(NSCLC)in the population with tumor proportion score(TPS)≥1%of PD-L1,and provide some reference for the clinical use and future price negotiation of pembrolizumab.Methods Based on Pubmed database,the published RCT literatures of pembrolizumab were analyzed,and the survival data were extracted,combined with the treatment plan of a tertiary hospital,the Markov model were established to simulate the cost and health effectiveness of patients for twenty years,and the stability of the model was tested by one-way sensitivity analysis and probability sensitivity analysis.Results Twenty years later,the cost-effectiveness ratio of pembrolizumab group and chemotherapy group was ￥58 517.60/quality adjusted life month(QALM)and ￥41 213.08/QALM.Compared with the chemotherapy group,the incremental cost effective ratio(ICER)was ￥104 485.36/QALM.Conclusion When the willingness to pay(WTP)value was ￥30 902/QALM,the pembrolizumab therapy was not more cost-effective advantages than platinum chemotherapy,and the sensitivity analysis showed that the results of the model were relatively stable.

ObjectiveTo explore the research status and trends of cohort studies on traditional Chinese medicine （TCM） efficacy evaluation from 2017 to 2022 and provide ideas and references for research in this field. MethodsSix databases including Pubmed， Web of Science， Embase， Scopus， Cochrane Library and CNKI were searched from January 1st， 2017 to December 31st， 2022. The total number of annual publications， journals， highly cited literatures， and keywords were quantitatively and visually analyzed by Bibliometrix. ResultsA total of 328 articles were included， which were published in 141 journals. The number of articles published in this field showed an overall upward trend， and retrospective cohort studies （282 papers， 85.98%） accounted for the largest proportion. A total of 151 cohort studies （46.04%） were conducted based on the database and showed an overall upward trend. The subjects were mainly patients with tumors （77 papers， 23.48%）， and cardiovascular and cerebrovascular diseases （64 papers， 19.51%）. The top 3 highly cited literatures mainly explore the association between TCM and survival outcome and quality of life in patients with malignant tumors. Fourteen and twenty-five high-frequency keywords were included in Chinese and English literature respectively， which formed 3 clusters such as research methods， statistical analysis and diseases. ConclusionIt was the current status to focus on retrospective cohort studies and focus on patients with tumors or cardiovascular and cerebrovascular diseases. Using observational database to conduct cohort studies of TCM efficacy evaluation could be the future research direction.

Objectives:To explore the effects of interatrial shunt on cardiac function and clinical prognosis of patients with heart failure with reduced ejection fraction(HFrEF). Methods:This study was a prospective single-arm study.From December 2021 to December 2022,15 consecutive patients with HFrEF from Beijing Anzhen Hospital were enrolled in this study.Interatrial shunt was performed with a D-Shant atrial shunt device.Right heart catheterization was performed before and immediately after device implantation,pulmonary capillary wedge pressure(PCWP),mean right atrial pressure(RAP),interatrial gradient pressure,mean pulmonary artery pressure,total pulmonary resistance(TPR),pulmonary vascular resistance(PVR),cardiac index(CI),and pulmonary/systemic blood flow ratio(Qp/Qs)were measured.Patients were followed-up for 12 months after procedure,changes in cardiac structure and function were evaluated by echocardiography.NYHA classification,6-minute walking distance(6MWD),and Kansas City cardiomyopathy questionnaire(KCCQ)were observed.All-cause mortality and rehospitalization for heart failure served as clinical endpoints. Results:Interatrial shunt procedure was successful in all patients.Compared with preoperative value,PCWP,interatrial gradient pressure,mean pulmonary artery pressure,and TPR were significantly decreased,while Qp/Qs was significantly increased immediately after procedure(all P<0.01).There were no significant changes in RAP,PVR,and CI post procedure(all P>0.05).There were no significant differences in shunt size,shunt velocity,and shunt pressure difference between postoperative immediately and at 12-months follow-up(all P>0.05).At 12 months,left ventricular ejection fraction was significantly higher than baseline level(P<0.05),and there were no significant changes in right atrial diameter and right ventricular fractional area change(both P>0.05).Compared with preoperative status,NYHA classification was improved,KCCQ score was increased,and the number of patients with 6MWD>450 m was increased at 12 months(all P<0.05).N-terminal pro-B-type natriuretic peptide value was significantly decreased at 12 months(P<0.05).No patient died during the 12-months follow-up period,and there were no device-related adverse events.Two patients experienced hospital readmission for heart failure. Conclusions:Implantation of interatrial shunt device could effectively improve hemodynamic parameters in patients with HFrEF and is related to significantly improved cardiac function at 12-months follow-up.

Objective:To discuss the protective effect of carnosine(CAR)against oxygen-glucose deprivation/reoxygenation(OGD/R)-induced astrocyte(AS)injury,and to clarify its possible mechanism.Methods:The AS were divided into control group,model group(OGD/R group),OGD/R+CAR group(CAR group),and OGD/R+CAR+AMP-activated protein kinase(AMPK)activator AICAR group(CAR+AICAR group).MTT assay and green cyanine staining method were used to detect the survival rates and green cyanine staining positive rates of the AS in various groups;Annexin V-FITC/PI method and flow cytometry were used to detect the apoptotic rates of the AS in various groups;Western blotting method was used to detect the expression levels of AMPK,phosphorylated AMPK(p-AMPK),mammalian target of rapamycin(mTOR),phosphorylated mTOR(p-mTOR),microtubule-associated protein light chain 3B(LC3B),Beclin-1,and P62 proteins in the AS in various groups;immunofluorescence staining was used to observe the LC3B positive fluorescence intensities in the AS in various groups.Results:Compared with control group,the survival rate and green cyanine staining positive rate of the AS in OGD/R group were decreased(P＜0.01),the apoptotic rate of the AS was increased(P＜0.01),the ratios of p-AMPK/AMPK and LC3B Ⅱ/LC3B Ⅰ and the expression level of Beclin-1 protein were increased(P＜0.01),and the ratio of p-mTOR/mTOR and the expression level of P62 protein were decreased(P＜0.01).Compared with OGD/R group,the survival rate and green cyanine staining positive rate of the AS in CAR group were increased(P＜0.01),the apoptotic rate of the AS was decreased(P＜0.01),the ratios of p-AMPK/AMPK and LC3B Ⅱ/LC3B Ⅰ and the expression level of Beclin-1 protein were decreased(P＜0.01),and the ratio of p-mTOR/mTOR and the expression level of P62 protein were increased(P＜0.01).Compared with CAR group,the survival rate and green cyanine staining positive rate of the AS in CAR+AICAR group were decreased(P＜0.01),the apoptotic rate of the AS was increased(P＜0.01),the ratios of p-AMPK/AMPK and LC3B Ⅱ/LC3B Ⅰ and the expression level of Beclin-1 protein were increased(P＜0.01),and the ratio of p-mTOR/mTOR and the expression level of P62 protein were decreased(P＜0.01).The LC3B immunofluorescence staining results were consistent with the Western blotting results.Conclusion:CAR has the protective effect on injury of the AS induced by OGD/R,and its molecular mechanism may be related to the inhibition of the AMPK/mTOR signaling pathway,thereby inhibiting autophagy.

OBJECTIVE To establish high performance liquid chromatography(HPLC)fingerprints of the extract of Fructus Li-gustri Lucidi-Ecliptae Herba and to identify the structure of its chemical constituents.METHODS The chromatographic separation was performed on ZORBAX Extend C18(250 mm×4.6 mm,5 μm)column with the mobile phase consisting of acetonitrile and 0.1%formic acid solution in gradient elution mode at a flow rate of 1.0 mL·min-1.The optimum column temperature was set at 35℃,the detection wavelength was 265 nm,and the injection volume was 10 μL.The HPLC fingerprints of 15 batches of herb pair from different origins were established.Then,similarity evaluation,cluster analysis,and orthogonal partial least squares discriminant analysis were carried out.The chemical structures of the constituents of the herb pair were identified based on the high-resolution mass spectrometry utilizing the UPLC-Q-Exactive Orbitrap MS in positive and negative-ion modes.RESULTS As a result,the similarity of the 15 bat-ches of samples varied from 0.865 to 0.992.A total of 16 common peaks were identified in the fingerprints,and 7 of them were identi-fied by comparision with the reference substances.Furthermore,55 chemical compounds were detected,and 7 of them were accurately identified based on the reference substances,and the chemical structures of the rest 48 components were temporarily speculated.CON-CLUSION The fingerprint method established in this study is simple,reliable,and reproducible,and can be further used for the quality control of Fructus Ligustri Lucidi-Ecliptae Herba herb pair.The developed UPLC-Q-Exactive Orbitrap MS method can be applied to identify the structures of chemical constituents in this herb pair and lay a foundation for further research.

A young female patient with acne and elevated testosterone level underwent plasma steroid hormones testing and found a significant increase in aldosterone. We excluded testing interference and verified the absence of hypertension, hypokalemia, and adrenal occupancy, as well as primary and secondary hyperaldosteronism. During follow-up, a temporal correlation was found between aldosterone levels and the use of drospirenone and ethinylestradiol tablets. It was observed that the combination of drospirenone and ethinylestradiol could lead to the increase of aldosterone level and the concentration ratio of aldosterone to direct renin through different mechanisms. Drospirenone exerts an antagonistic effect on mineralocorticoid receptor to prevent the development of hypertension or hypokalemia. In clinical practice, it is necessary to pay attention to the effect of this drug on screening markers for primary aldosteronism. In the laboratory examination, when female patients with no symptoms of hypertension and hypokalemia but with elevated aldosterone levels are encountered, it can be verified whether they have a history of use of compound estrogen-progestin such as drospirenone and ethinylestradiol tablets, and appropriate tips are provided in the report.

Objective To evaluate the perioperative safety and feasibility of day-case transurethral holmium laser enucleation of prostate(HoLEP)under over-night mode.Method From January 2021 to March 2023,83 patients of benign prostatic hyperplasia(BPH)were elected and treated with HoLEP by the one surgeon.According to different management methods,these patients were divided into the over-night day-case HoLEP group and the ordinary HoLEP group.Again,these patients were divided into large volume(≥50 mL)group and small volume(<50 mL)group according to the prostate volume.Record the age and perioperative data of all patients[total prostate volume,prostate resection weight,proportion of prostate resection,operating time,changes in peripheral venous blood hemoglobin(Hb),bladder flushing duration,catheter insertion duration,and success rate of first tube removal],the parameters of each group were compared.Result All of the 83 patients undergoing HoLEP surgery in this study,and there were no cases of HoLEP related reoperation or readmission.Among them,there were 43 cases in the over-night HoLEP group,aged 57～90 with an average of(70.1±7.3)years old,and the prostate volume was 29～161 mL with an average of(63.0±28.8)mL,All of them were discharged within 24 h,and there were no cases transferred to the ordinary HoLEP group,the success rate of first tube removal was 88.4%(38/43),and with average catheterization duration was(17.8±3.6)h;The other 40 cases were included into the ordinary HoLEP group,aged 55～87 with an average of(70.4±8.2)years old,the volume of the prostate was 22～118 mL with an average of(59.4±29.0)mL,the success rate of first tube removal was 90.0%(36/40),and with average catheterization duration was(77.5±25.1)h;There was no statistically significant difference in the perioperative parameters(total prostate volume,prostate resection weight,proportion of prostate resection,operating time,changes in peripheral venous blood Hb,and bladder flushing time)between the two groups(P>0.05),while the difference in catheter duration was statistically significant(P<0.01).Conclusion Regardless of the size of the prostate volume,day-case HoLEP is safe and feasible.Day-case HoLEP under the over-night mode is suitable for widespread and routine implementation in China,especially in medical centers with rich experience of HoLEP.