Objective : To predict and validate key targets for cisplatin(DDP) resistance in colorectal cancer(CRC) to provide more options for precision medicine in clinical treatment. Methods: Differentially expressed genes(DEGs) between normal colonic mucosa and CRC were screened from the gene expression omnibus(GEO) database. Key genes were identified using the STRING database and Cytoscape software. DEGs were subjected to enrichment analysis using the gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) databases. Key targets were validated through RNA-seq, qRT-PCR, and Western blot. The versican(VCAN) gene overexpression vector was transfected into human ileocecal colorectal adenocarcinoma cell line HCT8, and cell viability was assessed using the CCK-8 assay. Flow cytometry was used to assess apoptosis and cell cycle distribution. qRT-PCR and Western blot were performed to detect mRNA and protein levels of the target genes. Results : In this study, 118 upregulated DEGs and 146 downregulated DEGs were identified from the GEO database. DEGs were mainly enriched in extracellular matrix degradation, extracellular matrix organization, and the phosphoinositide 3-kinase(PI3K)-protein kinase B(AKT) signaling pathway. Based on protein-protein interaction network analysis, 20 hub genes were identified. By comparing the transcriptome sequencing results of the HCT8 parental strain and DDP-resistant strain, the VCAN gene was further selected. In CRC tissues, the expression level of VCAN was higher than that in normal colonic mucosa, and patients with high VCAN expression had shorter overall survival(OS) and recurrence free survival(RFS) times. Overexpression of VCAN in CRC cells promoted cell proliferation(P<0.05), increased resistance to DDP, reduced DDP-induced apoptosis(P<0.05), and G0/G1phase arrest(P<0.05); upregulation of VCAN activated the protein kinase B(AKT)-mammalian target of rapamycin(mTOR) signaling pathway. Conclusion Bioinformatics and transcriptome sequencing identified VCAN as a key target gene for DDP resistance in CRC, potentially promoting CRC progression and DDP resistance by regulating the AKT-mTOR pathway.

Objective:To identify genetic etiology of ischemic stroke(IS)based on pleiotropy of obe-sity related genes.Methods:A discordant sib-pair study was designed based on the Fangshan family co-hort in Beijing.Body mass index(BMI)polygenic risk score(PRS)was first constructed under different P values.Using the polygenic transmission disequilibrium test(pTDT),we then compared the actual BMI genetic risk of siblings with IS to their expected risk,to analyze whether higher BMI was over-trans-mitted to siblings with IS.The single nucleotide polymorphism(SNP)that comprised the PRS over-trans-mitted with IS and that corresponded to the highest heritability of IS were identified as a pleiotropy SNPs set between BMI and IS.This set was then utilized as a candidate set to identify and verify risk SNPs as-so-ciated IS by transmission disequilibrium test.Finally,we identified independent genomic risk loci and mapped to genes,we then explored the biological function of the identified risk loci and genes by func-tional annotation and pathway enrichment.Results:A total of 541 participants were enrolled,with an average age of(58.4±8.1)years,including 326 discordant sib pairs of ischemic stroke.Compared with non-IS participants,IS participants with males,education level below junior high school,hypertension and hyperlipidemia accounted for a higher proportion(P＜0.05).For all the BMI PRS,we found that the actual genetic risk of BMI in siblings with IS was higher than their expectation,suggesting that genetic risk associated with high BMI was over-transmitted with IS.Compared with other SNP sets,the set(P＜5 × 10-4)corresponded to the best analytical statistics of pTDT and the highest heritability of IS and was identified as the pleiotropy SNP set between BMI and IS.Within this set,there were 45 SNPs having linkage and association with IS,which were located in 43 independent genomic risk loci and mapped to 40 genes.These genes were significantly enriched in the lipid metabolism pathway.The rs2232852 cor-rected by multiple tests was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway.Conclusion:Pleiotropy between BMI-related genes and IS was observed.Forty-five SNPs were found with linkage and association with IS in the pleiotropy gene set and mapped to 40 genes,which were functionally enriched in lipid metabolic pathways.The rs2232852 corrected by multiple tests during association analysis validation was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway,suggesting that lipid metabolism and ferroptosis played an important role in the development of IS.

Objective To evaluate the accuracy of 6 commercial antibiotic susceptibility testing methods in detecting the sensitivity of carbapenems-resistant Klebsiella pneumoniae(CRKP)to tigecycline,and to provide an evidence for clinical laboratory to select the appropriate tigecyline susceptibility tests.Methods Non-duplicate CRKP clinically isolated from Aerospace Center Hospital from June 2023 to February 2024 were collected.60 cases of tigecycline intermediated CRKP[minimal inhibitery concentration(MIC)=4μg/ml]and 60 cases of drug-resistant CRKP(MIC≥8μg/ml)were screened by Vitek-2.The sensitivity of CRKP to tigecycline was detected by different methods.With the MIC test strip(MTS)as the reference method,the methodological evaluation of Vitek-2,commercial broth dilution method,E-test,Kirby-Bauer disk diffusion(KB)and disk combined with resensitization bufferwas carried out under the interpretation standards of the U S Food and Drug Administration(FDA)and the European Commission for Drug Susceptibility Testing(EUCAST),respectively.Results For the intermediate strains,under the FDA criteria,both the commercial broth dilution method and the disk combinedwith resensitization buffer method showed high consistency with the MTS method and were acceptable,whereas under the EUCAST criteria,all five methods were unacceptable.For the resistant strains,no matter what standard was,CA of all five methods were less than 90%,which were unacceptable.For all strains as a whole,the results were consistent with those of the resistant ones.Conclusion Under the current sample size,none of the five methods met the acceptable standards,especially not suitable for the recheck of strains with higher MICs.Commercial broth dilution method have the highest consistency with MTS,and it is worth expanding the sample size for further study.

Objective To systematically investigate biomechanical characteristics of one-finger Zen push method applied at the Fengchi acupoint under different force conditions,in order to provide precise quantitative data and enhance the treatment efficacy.Methods Ten senior Tuina practitioners were recruited.The German Novel Pliance-X 32 Expert dynamic pressure distribution system was used to record the mechanical parameters during the application of one-finger Zen push at the Fengchi acupoint under three force intensities:light,medium,and heavy,for 3 minutes.Data from the stable 1-minute segment of the mechanical output was selected for data analysis,and key biomechanical parameters such as the maximum force,average force,peak pressure,mean pressure,force-time integral(FTI),pressure-time integral(PTI),and operational frequency were evaluated.Results Under light,medium,and heavy force conditions,the mean maximum force applied by senior Tuina practitioners at the Fengchi acupoint were 6.31,9.45,and 18.27 N,respectively,while the mean force were 3.31,5.64,and 9.05 N,respectively.The mean peak pressures were 26.10,34.80,and 70.00 kPa,while the mean pressures were 11.95,21.00,and 26.15 kPa,respectively.The mean FTIs were 55.65,182.10,and 225.21 N·s,and the mean PTIs were 167.10,489.59,and 795.83 kPa·s,respectively.The mean operational frequencies were 156.00,150.60,and 154.80 times/min,respectively.Conclusions Ten senior Tuina practitioners showed a high degree of consistency between their subjective definitions of light,medium,and heavy force and the objectively measured mechanical parameters.This reflected their precise control over the applied force under different force conditions,verifying the practicality and reproducibility of the one-finger Zen push method in clinical applications.This study provides a reliable basis for quantitative research and development of standardized clinical operation guidelines.

Objective To evaluate the accuracy of 6 commercial antibiotic susceptibility testing methods in detecting the sensitivity of carbapenems-resistant Klebsiella pneumoniae(CRKP)to tigecycline,and to provide an evidence for clinical laboratory to select the appropriate tigecyline susceptibility tests.Methods Non-duplicate CRKP clinically isolated from Aerospace Center Hospital from June 2023 to February 2024 were collected.60 cases of tigecycline intermediated CRKP[minimal inhibitery concentration(MIC)=4μg/ml]and 60 cases of drug-resistant CRKP(MIC≥8μg/ml)were screened by Vitek-2.The sensitivity of CRKP to tigecycline was detected by different methods.With the MIC test strip(MTS)as the reference method,the methodological evaluation of Vitek-2,commercial broth dilution method,E-test,Kirby-Bauer disk diffusion(KB)and disk combined with resensitization bufferwas carried out under the interpretation standards of the U S Food and Drug Administration(FDA)and the European Commission for Drug Susceptibility Testing(EUCAST),respectively.Results For the intermediate strains,under the FDA criteria,both the commercial broth dilution method and the disk combinedwith resensitization buffer method showed high consistency with the MTS method and were acceptable,whereas under the EUCAST criteria,all five methods were unacceptable.For the resistant strains,no matter what standard was,CA of all five methods were less than 90%,which were unacceptable.For all strains as a whole,the results were consistent with those of the resistant ones.Conclusion Under the current sample size,none of the five methods met the acceptable standards,especially not suitable for the recheck of strains with higher MICs.Commercial broth dilution method have the highest consistency with MTS,and it is worth expanding the sample size for further study.

Objective To systematically investigate biomechanical characteristics of one-finger Zen push method applied at the Fengchi acupoint under different force conditions,in order to provide precise quantitative data and enhance the treatment efficacy.Methods Ten senior Tuina practitioners were recruited.The German Novel Pliance-X 32 Expert dynamic pressure distribution system was used to record the mechanical parameters during the application of one-finger Zen push at the Fengchi acupoint under three force intensities:light,medium,and heavy,for 3 minutes.Data from the stable 1-minute segment of the mechanical output was selected for data analysis,and key biomechanical parameters such as the maximum force,average force,peak pressure,mean pressure,force-time integral(FTI),pressure-time integral(PTI),and operational frequency were evaluated.Results Under light,medium,and heavy force conditions,the mean maximum force applied by senior Tuina practitioners at the Fengchi acupoint were 6.31,9.45,and 18.27 N,respectively,while the mean force were 3.31,5.64,and 9.05 N,respectively.The mean peak pressures were 26.10,34.80,and 70.00 kPa,while the mean pressures were 11.95,21.00,and 26.15 kPa,respectively.The mean FTIs were 55.65,182.10,and 225.21 N·s,and the mean PTIs were 167.10,489.59,and 795.83 kPa·s,respectively.The mean operational frequencies were 156.00,150.60,and 154.80 times/min,respectively.Conclusions Ten senior Tuina practitioners showed a high degree of consistency between their subjective definitions of light,medium,and heavy force and the objectively measured mechanical parameters.This reflected their precise control over the applied force under different force conditions,verifying the practicality and reproducibility of the one-finger Zen push method in clinical applications.This study provides a reliable basis for quantitative research and development of standardized clinical operation guidelines.

Objective:To identify genetic etiology of ischemic stroke(IS)based on pleiotropy of obe-sity related genes.Methods:A discordant sib-pair study was designed based on the Fangshan family co-hort in Beijing.Body mass index(BMI)polygenic risk score(PRS)was first constructed under different P values.Using the polygenic transmission disequilibrium test(pTDT),we then compared the actual BMI genetic risk of siblings with IS to their expected risk,to analyze whether higher BMI was over-trans-mitted to siblings with IS.The single nucleotide polymorphism(SNP)that comprised the PRS over-trans-mitted with IS and that corresponded to the highest heritability of IS were identified as a pleiotropy SNPs set between BMI and IS.This set was then utilized as a candidate set to identify and verify risk SNPs as-so-ciated IS by transmission disequilibrium test.Finally,we identified independent genomic risk loci and mapped to genes,we then explored the biological function of the identified risk loci and genes by func-tional annotation and pathway enrichment.Results:A total of 541 participants were enrolled,with an average age of(58.4±8.1)years,including 326 discordant sib pairs of ischemic stroke.Compared with non-IS participants,IS participants with males,education level below junior high school,hypertension and hyperlipidemia accounted for a higher proportion(P＜0.05).For all the BMI PRS,we found that the actual genetic risk of BMI in siblings with IS was higher than their expectation,suggesting that genetic risk associated with high BMI was over-transmitted with IS.Compared with other SNP sets,the set(P＜5 × 10-4)corresponded to the best analytical statistics of pTDT and the highest heritability of IS and was identified as the pleiotropy SNP set between BMI and IS.Within this set,there were 45 SNPs having linkage and association with IS,which were located in 43 independent genomic risk loci and mapped to 40 genes.These genes were significantly enriched in the lipid metabolism pathway.The rs2232852 cor-rected by multiple tests was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway.Conclusion:Pleiotropy between BMI-related genes and IS was observed.Forty-five SNPs were found with linkage and association with IS in the pleiotropy gene set and mapped to 40 genes,which were functionally enriched in lipid metabolic pathways.The rs2232852 corrected by multiple tests during association analysis validation was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway,suggesting that lipid metabolism and ferroptosis played an important role in the development of IS.

Objective To evaluate the efficacy of Huachansu tablets combined with transarterial chemoembolization(TACE)for treatment of primary hepatocellular carcinoma(HCC)and prognostic influence factors.Methods One hundred and eight patients with HCC were recruited according to the inclusion and exclusion criteria.Patients were randomly divided into treatment group and control group.The treatment group was treated with Huachansu tablets combined with TACE,and the control group was treated with TACE alone,with overall survival time(OS)and progression-free survival time(PFS)as the evaluation indexes.The COX regression analysis was used to evaluate the survival and prognostic effects and their influence factors in both groups.Results A total of 108 HCC patients were enrolled.The OS was 13.5 months in treatment group and 9.2 months in control group;the PFS was 6.8 months in treatment group and 5.3 months in control group,and the differences were significant statistically(all P<0.05).Multivariate COX regression analysis showed that Child-Pugh grade and cirrhosis were the independent risk factors for PFS in HCC patients.Child-Pugh grade were the independent risk factors for OS in HCC patients.ALBI is a protective factor for OS in HCC patients.Conclusions The treatment of HCC by Huachansu tablets combined with TACE can delay the progression of HCC and prolong PFS and OS of the patients with HCC.Child-Pugh grade,cirrhosis status,and ALBI were important factors affecting the prognosis of the patients with HCC.

Background The Qingcaosha Reservoir is facing issues of algal blooms and eutrophication, and the resulting increase in the level of chlorination disinfection by-products in the water has been a major concern. Objective To evaluate the impact of "Algae Monitoring and Control Program in Qingcaosha Reservoir" (hereinafter referred to as the program) on the control of trihalomethanes (THMs) in conventional finished water. Methods From 2011 to 2019, water samples were collected from the Lujiazui Water Plant once per season, one sample each time, and the concentrations of four THMs (trichloromethane, dichlorobromomethane, monochlorodibromomethane, and tribromomethane) were measured in the samples. Using 2014 when the program was implemented as a cut-off point, the entire study period was divided into two phases: pre-implementation (2011–2013) and post-implementation(2014–2019). Segmented linear regression with interrupted time series analysis was applied to assess the concentrations and trends of THMs in the finished water before and after the program launch. Results The concentration of total THMs in finished water increased by 1.561 µg·L⁻¹ (P=0.010) for each season of time extension before launching the program. The change in the concentration of total THMs in finished water was not statistically significant after the program launch, but the THMs concentration showed a decreasing trend as the slope was −0.626 (P=0.001). From 2017 until the end of 2019, the average concentration of THMs in finished water of Lujiazui Water Plant dropped to 10 μg·L⁻¹ or less. Conclusions The algae and eutrophication control measures in Qingcaosha Reservoir have achieved good results, controlling THMs in finished water at a low level, and the trend of THMs has changed from a yearly increase pattern before the program to a yearly decrease pattern after the program.

Objective To explore the effect of Traditional Chinese Medicine's five-element music therapy com-bined with individualized emotional counseling intervention in patients with autoimmune liver disease of liver de-pression and spleen deficiency type.Methods 74 patients with autoimmune liver disease of liver depression and spleen deficiency type who were admitted to the hepatology department of a tertiary hospital from January 2021 to February 2022 were selected as research subjects,and they were divided into an experimental group and a control group by a random number table with 37 cases in each group.The control group was given routine treatment and nursing care,as well as Traditional Chinese Medicine's emotional nursing.The experimental group received Tradi-tional Chinese Medicine's five-element music therapy combined with individualized emotional counseling intervention on the basis of routine treatment and nursing care,with an intervention period of 4 weeks.The Generalized Anxiety Disorder Scale(GAD-7),Patient Health Questionnaire Depression Scale(PHQ-9)and Pittsburgh Sleep Quality Index(PSQI)were used to evaluate patients within 24 hours after admission and after 4 weeks of intervention.Results A total of 72 patients completed the study,with 36 in the experimental group and 36 in the control group.Before and after intervention,the scores of GAD-7,PHQ-9,and PSQI in the experimental group were compared,and the dif-ferences were statistically significant(P＜0.001).After the intervention,the GAD-7 score in the experimental group was(7.89±3.15),which was lower than(10.14±4.41)in the control group.The PHQ-9 score was(12.33±4.08)in the ex-perimental group,which was lower than(14.64±5.34)in the control group.The PSQI score was(12.39±3.06)points,which was lower than(14.22±3.37)in the control group,and the differences were statistically significant(P＜0.05).Conclusion The application of Traditional Chinese Medicine's five-element music therapy combined with individual-ized emotional guidance intervention can effectively improve the sleep quality and help alleviate negative emotions in patients with liver depression and spleen deficiency type of autoimmune liver disease.