Purpose The study aimed to analyze the relationship between MET gene variants and clinicopathologi-cal features in patients with non-small cell lung cancer(NSCLC).Methods Next-generation sequencing technology was used to detect MET gene variants in NSCLC specimens.The association between MET gene variant status and clini-copathological features was then analyzed.Results Among 1 633 cases of NSCLC,the overall MET mutation rate was 4.53％(74/1 633).Variants were mainly observed in male patients,never-smokers,those older than 60 years,ade-nocarcinoma histology,and patients with TNM stage Ⅲ+Ⅳ disease(P＜0.05).MET gene variant status showed no significant assocication with patient age,sex,smoking history,or pathological subtype(P＞0.05),but was statistical-ly correlated with clinical stage and presence of distant metastasis(P＜0.05).The two major variant types were MET exon 14 skipping and MET amplification,which together accounted for 71.62％of all variants.In addition,MET am-plification was positively correlated with EGFR(P=0.003,rs=0.340)and TP53 mutations(P=0.002,rs=0.362),but showed no correlation with KRAS or ALK gene mutations.In contrast,MET exon 14 skipping was nega-tively correlated with EGFR gene mutations(P＜0.001,rs=-0.409),and showed no significant correlation with KRAS,ALK,or TP53 mutations.Conclusion Different types of MET gene variants(amplification,exon 14 skip-ping,fusion,and others)are significantly associated with clinical advanced clinical stage and distant metastasis in NSCLC,but are independent of patient age,sex,smoking history,and pathological subtype.MET amplification fre-quently co-occur with EGFR and TP53 co-mutations.

AIM To optimize the extraction process for total polyphenols from Conioselinum vaginatu(Spreng.)Thell.,make component analysis,and evaluate their anti-oxidant,hypoglycemic activities.METHODS The effects of ultrasound,enzymatic hydrolysis,acid hydrolysis,alcohol extraction and hydrolysis processes on the extraction quantity of total polyphenols were investigated,respectively.With extraction temperature,extraction time,ethanol concetration and liquid-solid ratio as influencing factors,extraction quantity of total polyphenols as an evaluation index,the extraction process was optimized by response surface method.HPLC was adopted in the identification of polyphenolic composition and determination of their contents.Subsequently,total polyphenols' scavenging capacities on DPPH,ABTS,OH free radicals,total reducing power and inhibitory capacity on α-glucosidase were determined.RESULTS The highest extraction quantity of total polyphenols was observable when extraction process was employed.The optimal conditions were determined to be 62 ℃ for extraction temperature,54 min for extraction time,69％for ethanol concentration,and 50∶1 for liquid-solid ratio,the extraction quantity of total polyphenols was(9.51±0.2)mg GAE/g.Seven constituents existed in C.vaginatu,among which ferulic acid demonstrated the highest content,followed by that of myricetin,while D-tryptophan content was the lowest.At the concentration of 7.61 mg/L,total polyphenols displayed the scavenging rates on DPPH,ABTS,OH free radicals of 80.70％,85.97％,28.60％,total reducing power of 0.22,and inhibition rate on α-glucosidase of 77.23％,respectively.CONCLUSION This stable and reliable method can be used for the extraction of total polyphenols from C.vaginatum with strong anti-oxidant,hypoglycemic activities.

Objective To investigate the relationship between deep medullary vein(DMV)score and enlarged perivascular space(EPVS)score with cranial MRI to explore the mechanisms of EPVS occurrence and development.Methods Totally 118 patients with cerebral small vessel disease in some hospital had their clinical and imaging data analyzed retrospectively.On T2-weighted images,EPVS scores ranging from 0 to 4 were assigned to the basal ganglia and centrum semiovale regions based on the number of EPVS.For DMV scoring on magnetic susceptibility weighted images,the brain lobes were divided into six regions,including bilateral frontal,parietal and occipital lobes,and scored according to the significance and continuity of the DMV signals(0 to 3 points),and the scores of the regions were summed up as the total DMV score(0 to 18 points).Spearman correlation analysis was employed to investigate the correlation between DMV and EPVS scores.Kruskal-Wallis test was used to analyze the differences among groups with different EPVS scores.Additionally,multinomial ordinal regression analysis was conducted to explore the factors influencing EPVS.Results No significant correlation was found between EPVS scores in centrum semiovale and DMV scores(r2=0.015,P=0.191),while DMV scores and EPVS scores in basal ganglia showed a significant positive correlation(r2=0.558,P<0.000 1).Univariate analysis revealed statisti-cally significant differences in age,hypertension and DMV scores when different scoring groups of EPVS in the basal ganglia region were compared(P<0.05);multinomial ordinal regression analysis showed that age,hypertension and DMV scores were independently correlated with EPVS scores in the basal ganglia region.Conclusion There is a positive correlation between DMV scores and EPVS scores in the basal ganglia.Age,hypertension,and DMV score are independent influe-ncing factors for EPVS in the basal ganglia region.[Chinese Medical Equipment Journal,2025,46(4):52-56]

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

In recent years,increasingly diverse methods have been employed to prevent and treat radiation enteritis(RE).Improvements in radiotherapy techniques,optimization of radiation dose fractionation,and development and use of radioprotective agents have reduced the incidence of RE,and new treatment modalities,including hormones,mucosal protectants,endoscopic treatments,and surgical interventions,together with emerging therapies,including microbiome-based treatments,stem cell transplantation,and hyperbaric oxygen therapy,have made significant progress.These new technologies and treatments exhibit potential efficacy at alleviating symptoms,protecting the intestin-al barrier,promoting tissue repair,and restoring intestinal microbiota balance.Here,we review the latest research investigating treatment and prevention of RE,exploring the optimization of radiation therapy techniques,and developing strategies for prevention and treatment,with the aim of providing a theoretical basis for more precise,comprehensive,and effective treatment options for RE.

Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38％)and primary myocardial cells(the inhibition rate was 49.7％,with P＜0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P＜0.01),decreasing the hy-drated particle size(P＜0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.

Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38％)and primary myocardial cells(the inhibition rate was 49.7％,with P＜0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P＜0.01),decreasing the hy-drated particle size(P＜0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.

This article discusses the structure, function, signaling pathways, and disease associations of the serine protease inhibitors(SERPINS)family. The SERPINS family antagonizes the activity of serine proteases and plays critical roles in various biological processes, including coagulation, fibrinolysis, inflammatory responses, and immune modulation. SERPINS possess a conserved secondary structure and function through an irreversible suicide inhibition mechanism. Their dysfunction is associated with a multitude of clinical diseases, such as deep vein thrombosis, emphysema, dementia, and neurodegenerative disorders. Reviewing several key members of the SERPINS family, such as SERPINA1,SERPINA5,SERPINB2,SERPINC1 and SERPINE1, their physiological roles and functions, and their roles in related diseases, is of significant importance for further research into these conditions.

Objective To investigate the relationship between deep medullary vein(DMV)score and enlarged perivascular space(EPVS)score with cranial MRI to explore the mechanisms of EPVS occurrence and development.Methods Totally 118 patients with cerebral small vessel disease in some hospital had their clinical and imaging data analyzed retrospectively.On T2-weighted images,EPVS scores ranging from 0 to 4 were assigned to the basal ganglia and centrum semiovale regions based on the number of EPVS.For DMV scoring on magnetic susceptibility weighted images,the brain lobes were divided into six regions,including bilateral frontal,parietal and occipital lobes,and scored according to the significance and continuity of the DMV signals(0 to 3 points),and the scores of the regions were summed up as the total DMV score(0 to 18 points).Spearman correlation analysis was employed to investigate the correlation between DMV and EPVS scores.Kruskal-Wallis test was used to analyze the differences among groups with different EPVS scores.Additionally,multinomial ordinal regression analysis was conducted to explore the factors influencing EPVS.Results No significant correlation was found between EPVS scores in centrum semiovale and DMV scores(r2=0.015,P=0.191),while DMV scores and EPVS scores in basal ganglia showed a significant positive correlation(r2=0.558,P<0.000 1).Univariate analysis revealed statisti-cally significant differences in age,hypertension and DMV scores when different scoring groups of EPVS in the basal ganglia region were compared(P<0.05);multinomial ordinal regression analysis showed that age,hypertension and DMV scores were independently correlated with EPVS scores in the basal ganglia region.Conclusion There is a positive correlation between DMV scores and EPVS scores in the basal ganglia.Age,hypertension,and DMV score are independent influe-ncing factors for EPVS in the basal ganglia region.[Chinese Medical Equipment Journal,2025,46(4):52-56]

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.