OBJECTIVE To systematically evaluate the efficacy and safety of different chemotherapy combination regimens for first-line treatment of metastatic colorectal cancer （mCRC）. METHODS PubMed， Cochrane Library， Embase and Web of Science were electronically searched to collect randomized controlled clinical trial （RCT） on first-line treatment for mCRC from January 1， 2000 to February 16， 2025. Two reviewers independently screened literature， extracted data and assessed the risk of bias of the included studies. Network meta-analysis was performed by using R4.4.3 and Stata 17.0 software. RESULTS A total of 28 RCTs， involving 16 intervention measures， were included. In terms of prolonging progression-free survival （PFS） and overall survival （OS）， FOLFOX （5-fluorouracil+oxaliplatin+calcium folinate regimen）+cetuximab had the highest probability of ranking first. In terms of improving objective response rate （ORR）， FOLFOXIRI （5-fluorouracil+oxaliplatin+irinotecan+calcium folinate regimen）+ bevacizumab and FOLFOX+bevacizumab+nivolumab had the highest probability of ranking first； in terms of the incidence of grade 3 or higher adverse reactions， FOLFOXIRI+panitumumab had the highest probability of ranking first； in subgroup analysis of KRAS wild-type patients， FOLFIRI （5-fluorouracil+irinotecan+calcium folinate regimen）+panitumumab and FOLFIRI+bevacizumab had the highest probability of ranking first in terms of prolonging PFS and OS， respectively； in terms of ORR， FOLFOXIRI+ cetuximab had the highest probability of ranking first. CONCLUSIONS In first-line treatment for mCRC， FOLFOX combined with targeted therapy has advantages in terms of efficacy and safety. However， individualized treatment strategies should be formulated based on the KRAS gene status and tumor location of patients.

Objective To investigate the relationship between polymorphism of resistin(RETN)gene and metabolic associated fatty liver disease(MAFLD)in type 2 diabetes mellitus(T2DM)patients in middle and high altitude areas.Methods A total of 400 patients with T2DM in Qinghai area were recruited and divided into simple T2DM group(T2DM,n=200)and T2DM combined with MAFLD group(T2DM+ MAFLD,n=200)according to liver ultrasonography.Healthy individuals confirmed by physical examination were selected as the normal control group(NC,n=180).Plasma resistin levels were measured by ELISA.The polymorphism of RETN-420C/G and +299G/A genes were detected by PCR sequencing.Results By comparing the polymorphism of RETN-420C/G gene in each group,it was found that the frequencies of G/G genotype and G allele frequency in T2DM+MAFLD group were higher than those in NC group and T2DM group(P<0.05),while the frequencies of C/C genotype and C allele frequency were lower than those in NC group and T2DM group(P<0.05).The risk of MAFLD increased by 1.571,2.126 and 1.537 times respectively in T2DM patients with C/G,G/G genotype and G allele.Logistic regression analysis showed that G/G genotype was a risk factor for MAFLD in T2DM patients.By comparing the polymorphism of RETN+299G/A gene in each group,it was found that A allele frequency in T2DM+MAFLD group was higher than that in NC group and T2DM group,while G allele frequency was lower than that in NC group and T2DM group(P<0.05).The allele A increased the risk of MAFLD in T2DM patients by 1.432 times compared to allele G.Conclusion RETN gene-420C/G locus G/G genotype increases the risk of T2DM combined with MAFLD in middle and high altitudeareas.

Olfactory receptors(ORs)are transmembrane proteins mainly distributed in olfactory sensory neurons of the nasal epithelium,mediating the transmission of real-time sensory signals to the brain to produce smell.Recent studies have reported that ORs can also be expressed in tissues or organs outside the nasal cavity,and are closely related to a variety of biological processes,such as sperm chemotaxis,wound healing,glycolipid metabolism and intestinal secretion.In addition,ORs are closely related to a variety of malignant tumors such as prostate cancer,breast cancer and colorectal cancer,and may affect the occurrence and development of tumors by regulating cell proliferation,apoptosis,migration and invasion.This review provides an overview of the effects of ectopic ORs on the function of various human tissues and organs and assesses their potential value as drug targets for the treatment of human diseases.

Objective To investigate the application value of spectral computed tomography venography(CTV)in the display and staging of deep venous thrombosis(DVT)in the lower extremity.Methods Eighty-two patients with CTV were selected and ran-domly divided into group A(42 patients)and group B(40 patients).Group A:tube voltage 120 kVp.Group B:gemstone spectral ima-ging(GSI)mode,reconstruction of 50 keV and iodine(water)maps.The CT and standard deviation(SD)values of the veins were measured,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were calculated in 120 kVp images of group A and in 50 keV images of group B.Two observers scored the image quality of the 2 groups subjectively,and Kappa test was used to examine the con-sistency.Based on the duration from the occurrence of clinical symptoms,the DVTs were classified.The CT values and iodine con-centration(IC)of DVT were measured in the 120 kVp images of group A and in the iodine(water)maps of group B,respectively.The receiver operating characteristic(ROC)curve was drawn to compare the effectiveness of CT values and IC in diagnosing DVT staging.Results CT values,SNR,and CNR of veins in group B were higher than those in group A(P<0.05).The subjective scores of the two groups were consistent(Kappa=0.926-0.955,P<0.05).The score for the display of veins and thrombus clarity in group B was 5(4,5),which was better than the score of 4(3,4)in group A(P<0.05).The efficiency of IC in diagnosing DVT staging[area under the curve(AUC)=0.973]was better than that of CT values(AUC=0.891).Conclusion The spectral CTV can improve the contrast of lower extremity deep veins and the clarity of thrombus,and can provide more objective indicators for the diagnosis of thrombus staging,which is conducive to accurate clinical diagnosis and treatment.

Objective To explore the influencing factors of visual acuity recovery in patients with high myopia after posterior chamber phakic intraocular lens(ICL)implantation.Methods A prospective study was conducted on 210 pa-tients(420 eyes)with high myopia who underwent ICL implantation at the Second Affiliated Hospital of Zhengzhou Univer-sity from May 2021 to March 2023.The patients were divided into a good recovery group[best corrected visual acuity(BC-VA)recovery ≥0.3 D]and a poor recovery group(BCVA recovery＜0.3 D)based on their visual acuity recovery status three months after surgery.The baseline data of patients in the two groups were compared,and the factors affecting visual acuity recovery were analyzed using Logistic regression.The receiver operating characteristic(ROC)curve was used to an-alyze the predictive value of the Logistic regression model for poor visual acuity recovery in patients with high myopia after ICL implantation.Results Three months after surgery,149 patients(298 eyes)were in the good recovery group,and 61 patients(122 eyes)were in the poor recovery group.There were no significant differences in gender,age,years of myopi-a,body mass index,and academic performance between the two groups(all P＞0.05).The proportions of patients with corneal astigmatism＜1.30 D(55.74％),corneal diopter＜45 D(59.02％),Pittsburgh Sleep Quality Index(PSQI)＜7 points(63.93％),and average central radius of curvature[(7.82±0.27)mm]in the poor recovery group were lower than those in the good recovery group[83.89％,81.88％,85.91％,and(7.90±0.24)mm,respectively].The central flat me-ridian curvature(k1)of the anterior corneal surface[(43.27±1.43)D],steep meridian curvature(k2)of the anterior corneal surface[(44.84±1.53)D],and arch height[(628.49±67.28)μm]in the poor recovery group were higher than those in the good recovery group[(42.73±1.42)D,(44.12±1.47)D],and[(417.56±80.14)pm],with significant differences(all P＜0.05).Logistic regression analysis showed that corneal astigmatism,corneal diopter,k1,k2,arch height,and PSQI score were independent influencing factors of poor visual acuity recovery after ICL implantation in pa-tients with high myopia(all P＜0.05).ROC curve analysis showed that the area under the ROC curve for predicting poor visual acuity recovery after ICL implantation in patients with high myopia by Logistic regression model was 0.938(95％CI:0.896-0.966),the sensitivity was 83.61％,and the specificity was 91.95％(P＜0.05).Conclusion The visual acuity recovery after ICL implantation in patients with high myopia is affected by corneal astigmatism,corneal diopter,k1,k2,arch height,and PSQI score.The Logistic regression model based on these factors has high predictive value for visual acui-ty recovery after ICL implantation.

Objective To assess the efficacy of pirfenidone combined with PD-L1 inhibitor for treatment of bladder cancer in a mouse model and its effect on tumor immune microenvironment modulation.Methods Forty C57BL/6 mouse models bearing ectopic human bladder cancer xenografts were randomized into control group,PD-L1 inhibitor group,pirfenidone group and combined treatment group(n=10).After successful modeling,PD-L1 inhibitor treatment was administered via intraperitoneal injection at 12.5 mg/kg every 3 days,and oral pirfenidone(500 mg/kg)was given on a daily basis.The survival rate of the mice and tumor growth rate were compared among the 4 groups.The expressions of CD3,CD8,CD45,E-cadherin and N-cadherin in the tumor tissues were detected with immunohistochemistry after the 21-day treatment,and bone marrow-derived suppressor cells(MDSCs)were observed with immunofluorescence staining;serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),urea nitrogen(BUN),creatinine(CRE)and lactate dehydrogenase(LDH-L)were analyzed using an automated biochemical analyzer.Results Treatment with PD-L1 inhibitor and pirfenidone alone both significantly decreased tumor growth rate and tumor volume at 21 days(P<0.05),but the combined treatment produced an obviously stronger inhibitory effect(P<0.05).PD-L1 inhibitor and pirfenidone alone significantly increased E-cadherin expression and decreased N-cadherin expression in the tumor tissue(P<0.05).The two treatments both significantly increased the percentage of CD3+,CD8 and CD45+ T cells and decreased the percentage of Ly-6G+CD11b+MDSCs in the tumor tissue,and these changes were more obvious in the combined treatment group(P<0.05).No significant differences were found in serum ALT,AST,BUN,CRE or LDH-L levels among the 4 groups(P>0.05).Conclusion Combined treatment with pirfenidone and PD-L1 inhibitor significantly inhibits the progression of bladder cancer in mice possibly by regulating tumor immune microenvironment and inhibiting epithelial-mesenchymal transition of the tumor cells.

Objective To explore the regulatory effect of miR-204-5p on biological behaviors of bladder cancer cells and its molecular mechanism.Methods Survival analysis and correlation analysis were performed using TCGA database to explore the association of miR-204-5p expression with survival outcomes and clinicopathological parameters of bladder cancer patients.The expression level of miR-204-5p was detected in bladder cancer and adjacent tissues and in normal uroepithelial cells and bladder cancer cells.In cultured bladder cancer cells,the effects of miR-204-5p overexpression and knockdown on cell proliferation,migration,invasion,and apoptosis were analyzed.Transcriptome sequencing,bioinformatics analysis and dual-luciferase assay were carried out to confirm targeted inhibition of RAB22A by miR-204-5p to promote malignant biological behaviors of bladder cancer cells.Results Patients with high miR-204-5p expressions had lowered median survival time and poor prognosis(P<0.05).The expression of miR-204-5p was significantly up-regulated in bladder cancer tissues and cells(P<0.05).In bladder cancer cells,miR-204-5p overexpression significantly promoted cell proliferation,migration and invasion and reduced cell apoptosis.Transcriptome sequencing,bioinformatics analysis and dual-luciferase assay all suggested that RAB22A was a key downstream factor of miR-204-5p.Overexpression of miR-204-5p significantly inhibited RAB22A expression in bladder cancer cells,and overexpression of RAB22A partially reversed miR-204-5p overexpression-induced enhancement of bladder cancer cell proliferation.Conclusion High expression of miR-204-5p promotes proliferation,migration and invasion and reduces apoptosis of bladder cancer cells by negatively regulating RAB22A expression.

Objective To assess the efficacy of pirfenidone combined with PD-L1 inhibitor for treatment of bladder cancer in a mouse model and its effect on tumor immune microenvironment modulation.Methods Forty C57BL/6 mouse models bearing ectopic human bladder cancer xenografts were randomized into control group,PD-L1 inhibitor group,pirfenidone group and combined treatment group(n=10).After successful modeling,PD-L1 inhibitor treatment was administered via intraperitoneal injection at 12.5 mg/kg every 3 days,and oral pirfenidone(500 mg/kg)was given on a daily basis.The survival rate of the mice and tumor growth rate were compared among the 4 groups.The expressions of CD3,CD8,CD45,E-cadherin and N-cadherin in the tumor tissues were detected with immunohistochemistry after the 21-day treatment,and bone marrow-derived suppressor cells(MDSCs)were observed with immunofluorescence staining;serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),urea nitrogen(BUN),creatinine(CRE)and lactate dehydrogenase(LDH-L)were analyzed using an automated biochemical analyzer.Results Treatment with PD-L1 inhibitor and pirfenidone alone both significantly decreased tumor growth rate and tumor volume at 21 days(P<0.05),but the combined treatment produced an obviously stronger inhibitory effect(P<0.05).PD-L1 inhibitor and pirfenidone alone significantly increased E-cadherin expression and decreased N-cadherin expression in the tumor tissue(P<0.05).The two treatments both significantly increased the percentage of CD3+,CD8 and CD45+ T cells and decreased the percentage of Ly-6G+CD11b+MDSCs in the tumor tissue,and these changes were more obvious in the combined treatment group(P<0.05).No significant differences were found in serum ALT,AST,BUN,CRE or LDH-L levels among the 4 groups(P>0.05).Conclusion Combined treatment with pirfenidone and PD-L1 inhibitor significantly inhibits the progression of bladder cancer in mice possibly by regulating tumor immune microenvironment and inhibiting epithelial-mesenchymal transition of the tumor cells.

Objective To explore the regulatory effect of miR-204-5p on biological behaviors of bladder cancer cells and its molecular mechanism.Methods Survival analysis and correlation analysis were performed using TCGA database to explore the association of miR-204-5p expression with survival outcomes and clinicopathological parameters of bladder cancer patients.The expression level of miR-204-5p was detected in bladder cancer and adjacent tissues and in normal uroepithelial cells and bladder cancer cells.In cultured bladder cancer cells,the effects of miR-204-5p overexpression and knockdown on cell proliferation,migration,invasion,and apoptosis were analyzed.Transcriptome sequencing,bioinformatics analysis and dual-luciferase assay were carried out to confirm targeted inhibition of RAB22A by miR-204-5p to promote malignant biological behaviors of bladder cancer cells.Results Patients with high miR-204-5p expressions had lowered median survival time and poor prognosis(P<0.05).The expression of miR-204-5p was significantly up-regulated in bladder cancer tissues and cells(P<0.05).In bladder cancer cells,miR-204-5p overexpression significantly promoted cell proliferation,migration and invasion and reduced cell apoptosis.Transcriptome sequencing,bioinformatics analysis and dual-luciferase assay all suggested that RAB22A was a key downstream factor of miR-204-5p.Overexpression of miR-204-5p significantly inhibited RAB22A expression in bladder cancer cells,and overexpression of RAB22A partially reversed miR-204-5p overexpression-induced enhancement of bladder cancer cell proliferation.Conclusion High expression of miR-204-5p promotes proliferation,migration and invasion and reduces apoptosis of bladder cancer cells by negatively regulating RAB22A expression.

Objective:To observe the characteristics and differences of gut microbiota in asthma patients with different inflammatory types through metagenomic analysis.Methods:Adults aged ≥18 years who visited the Respiratory Clinic of Peking University Third Hospital from August 1, 2021 to August 31, 2022 and were primarily diagnosed with asthma were selected as the study subjects. Finally, 29 patients with stable asthma were included. Fresh fecal samples were collected and the fecal DNA was extracted for high-throughput 16sRNA sequencing of gut microbiota. The diversity and community structure of gut microbiota in different groups of asthma patients were compared, and the species differences were analyzed through random forest and LEfSe analysis.Results:There were sex-based differences in asthma patients with different types of inflammation, and the proportion of female patients was higher in neutrophilic asthma patients ( χ2=4.14, P=0.042). There was no significant intergroup difference in the alpha diversity of gut microbiota among asthma patients with different inflammatory types, but there were significant differences in the microbiome. Patients with neutrophilic asthma had higher relative abundance of Bacillales ( P=0.029) and Oscillospiraceae ( P=0.015). In species LEfSe analysis, patients with eosinophilic asthma had a higher relative abundance of fungi. Conclusion:There are intergroup differences in the gut microbiota of asthma patients with different inflammation types, and fungi are biomarkers that distinguish the differences in gut microbiota between patients with eosinophilic asthma and neutrophilic asthma.