ObjectiveTo explore the effects of genetic variation of obesity-related biological pathways and gene-obesity interactions on the incidence of gastric cancer, so as to better understand the pathogenesis of gastric cancer and help identify high-risk populations for individualized prevention of gastric cancer. MethodsA case-control study based on the Shanghai Suburban Adult Cohort and Biobank study (SSACB) was conducted on the cases with gastric cancer. A total of 267 cases with gastric cancer and 267 healthy controls matched 1∶1 by age and gender using propensity score were included in the study. After genome-wide genotyping, quality control and imputation, 19 250 single nucleotide polymorphism (SNP) sites from 115 genes in 4 obesity-related biological pathways were extracted. Univariate and multivariate logistic regression analyses were used to evaluate the association between these SNP sites and the risk of gastric cancer, and false positive report probability (FPRP) was used for multiple test correction.Data from Biobank Japan (BBJ) and FinnGen public accessible databases were used to validate significant SNP sites. For validated sites, expression quantitative trait loci (eQTL) analysis and differentially expressed genes analysis were further performed. Additive and multiplicative interactions were used to evaluate the gene-obesity interactions on the incidence of gastric cancer. Additive interaction evaluation indicators included relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (SI), while multiplicative interaction evaluation indicators include OR_GxE and P_inter. ResultsA total of 41 SNP sites were significantly associated with the onset of gastric cancer (P_adj<0.05, FPRP_0.1<0.1), among which 7 groups of haplotype blocks were formed. ACACB/ rs2268401 [SSACB: P=0.005, BBJ: P=0.049], HRAS/ rs12785860 (SSACB: P<0.001, FinnGen: P=0.045), and PTPN1/ rs6095985 (SSACB: P<0.001, FinnGen: P=0.023) were significantly associated with the risk of gastric cancer after validation in different populations. Among which, the G allele of HRAS/ rs12785860 was correlated with the downregulation of HRAS mRNA expression (P<0.001), and the expression level of HRAS in gastric cancer tissues was higher than that in adjacent normal tissues (P<0.001). Additionaly, JAK1/rs11208559 showed a positive additive interaction with waist circumstance (WC) on the risk of gastric cancer [RERI=2.29(0.06~4.53), AP=0.57(0.23~0.90), SI=4.03(2.20~5.87)]. ConclusionObesity-related biological pathway SNP sites and their haplotypes are associated with the risk of gastric cancer, suggesting that genetic variations in obesity pathways may affect gastric cancer. The HRAS/ rs12785860 is significantly associated with downregulation of HRAS gene expression, which may serve as a potential genetic marker for gastric cancer. JAK1/rs11208559 interacts with obesity additively on the risk of gastric cancer. Individuals with GC+CC genotypes and pre-central or central obesity have an increased risk of gastric cancer, providing clues and evidences for individualized prevention of gastric cancer.

Objective:To evaluate the endometrial implantation window in patients with recurrent implantation failure using endometrial receptive array(ERA)sequencing or endometrial histological detection methods,and to explore the effectiveness and cost-effectiveness analysis of two technologies for improving clinical outcomes in such patients.Methods:A retrospective cohort study was conducted on clinical data of 125 patients diagnosed with repeated implantation failure in Gansu Maternal and Child Health Hospital from January 2018 to December 2022.According to whether endometrial receptivity testing was accepted and different detection techniques were used,they were divided into a control group(n=36),a genomic group(n=35),and a histological group(n=54).The clinical data and pregnancy outcomes of the three groups were compared.Results:①The results of one-way ANOVA showed that the embryo implantation rate in the genomic group and histological group was significantly higher than that in the control group,and the difference was statistically significant(P＜0.05).There was no sta-tistically significant difference in embryo implantation rate between genomic and histological groups(P=0.48).②There was no statistically significant difference in clinical pregnancy rate and live birth rate among the three groups(P＞0.05).③Log rank test showed:The time for 50％of patients to reach live labor was significantly shorter than that of the control group,and the difference was statistically significant(P＜0.05);There was no sta-tistically significant difference in the time to live birth in 50％of patients between the genomic and histological groups of 50％of patients(P＞0.05).④The average number of embryos transferred in the control group was significantly higher than that in the genomic and histological groups,with statistical significance(P＜0.05).The cost of genomic patients was significantly higher than that of histology group,and the difference was statistically significant(P＜0.05).Conclusions:①Endometrial implantation window detection is feasible for patients with re-peated implantation failure,which can effectively shorten the time to live birth and reduce the number of transplan-ted embryos;②Both ERA sequencing and endometrial histology detection have limitations as methods to evaluate endometrial implantation window,and it is not clear which detection method has more advantages in accuracy and practicability.

Rosacea is a common chronic inflammatory skin disease whose exact pathogenesis has not been fully elucidated. Metabolomics has been widely used in the field of life science to provide strong evidence for exploring the pathogenesis and biomarkers of diseases. In recent years, researchers have applied metabolomics to rosacea-related fields using sebum, tear, saliva, and serum samples. This review summarizes research progress on current metabolomics methods and the application of metabolomics in rosacea.

Rosacea is a chronic recurrent inflammatory skin disease, and correct assessment of clinical symptoms and severity may facilitate treatment options. This review summarizes a range of subjective, semi-subjective and objective methods currently used in the assessment of rosacea severity, in order to provide useful tools for clinical assessment of rosacea severity and give guidance on treatment modification according to the therapeutic effect.

Background and purpose:With the aging population,the number of elderly patients with colorectal cancer(CRC)is increasing.To date,elderly patients with stage Ⅱ CRC often receive a weakened chemotherapy regimen or even no chemotherapy after radical surgery,and It is still unclear whether this will lead to adverse oncological outcomes.This study aimed to explore the prognostic impact of advanced age on stage Ⅱ CRC patients after removing bias through a multivariate COX regression approach.Methods:We retrospectively collected data of 3314 colorectal cancer patients with postoperative pathology of stage Ⅱ,no history of previous tumors,no secondary primary tumors within 5 years after surgery and no preoperative neoadjuvant therapy.This study was reviewed by the medical ethics committee of Fudan University Shanghai Cancer Center(ethics number:050432-4-2108*).The optimal threshold for calculating age relative to survival using survminer package of R software(version 3.0)(surv_cutpoint algorithm)was 73 years.We compared the clinical and pathological characteristics,overall survival(OS)and disease-free survival(DFS)between the older group(age＞73 years)and the younger group(age≤73 years).The alignment diagram prediction model was drawn using the survival package and RMS package.Results:The elderly and non-elderly groups were evenly comparable in terms of gender,tumor location,differentiation,vascular invasion,perineural invasion and pT stage.Multivariate COX regression showed that advanced age was an independent prognostic risk factor for OS[hazard ratio(HR)=3.725(3.051-4.549),P＜0.001]and DFS[HR=2.431(2.029-2.912),P＜0.001].The nomogram(alignment diagram)prediction model constructed based on multivariate COX regression could effectively evaluate the prognosis of stage Ⅱ CRC patients and provide guidance for practical clinical work.Conclusion:In stage Ⅱ CRC patients,older age is associated with shorter OS and DFS.Adequate intensity of adjuvant chemotherapy may be necessary.Treatment decisions can be adjusted based on the predicted model scores of the patient's alignment diagram.

Background and purpose:According to current consensus,adverse high-risk pathological features are only associated with adjuvant therapy for stage Ⅱ colorectal cancer(CRC).As important prognostic factors,we further explored the possibility of identifying patients with potential recurrence and poor prognosis based on these incorporating high-risk pathological features.Methods:This is a cohort study.A retrospective analysis was conducted on clinical data of CRC patients who underwent surgical treatment at the Second Department of Colorectal Surgery,Fudan University Affiliated Shanghai Cancer Center from 2008 to 2018.This study was approved by the Ethics Committee of the Fudan University Shanghai Cancer Center(approval No.:050432-4-2108*),and the study complies with the Declaration of Helsinki.A total of 9875 patients were enrolled,including 5859 males and 4016 females,aged[M(IQR)]60(16)years(range:16 to 94).Median follow-up time was 1779.0 days[95%CI:1750.1-1807.9].We used the Kaplan-Meier method to plot survival curves for different groups.Cox multivariate analysis was used to identify independent risk factors for 5-year overall survival(OS),disease-free survival(DFS)and recurrence-free survival(RFS).Finally,a column chart model was constructed to evaluate and stratify patient prognosis.The Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)checklist was followed for this cohort study.Results:According to the number of incorporating high-risk pathological features,patients were divided into five groups:Hr_0 group(0 incorporating high-risk pathological feature),Hr_1 group(1 incorporating high-risk pathological feature),Hr_2 group(2 incorporating high-risk pathological features),Hr_3 group(3 incorporating high-risk pathological features),and Hr_4 group(4 or more incorporating high-risk pathological features).The Kaplan-Meier survival curve results indicated significant differences in OS,DFS and RFS among different groups(all P<0.001).Subgroup analysis was conducted on stage Ⅱ colorectal cancer,and the survival curves of OS,DFS and RFS in different Hr groups overlapped with each other.Compared to the overall population,the survival differences in different groups were significantly reduced,indicating that stage Ⅱ colon cancer patients with incorporating high-risk pathological features may benefit from adjuvant chemotherapy.The independent prognostic factors for RFS included age,pT stage,pN stage and Hr group.The survival curves of OS,DFS and RFS indicated that the prognosis of Hr_4 group was significantly worse than that of stage Ⅲc patients;5.2%and 14.1%of stage Ⅰ and Ⅱ patients had two or more incorporating high-risk pathological features(Hr group≥2),respectively.Finally,a column chart model was constructed by incorporating the independent prognostic risk factors for CRC mentioned above.The calibration curve showed a good consistency between the actual observations and the predictions made by the nomogram,and the decision curve analysis(DCA)indicated that the model constructed in this study had good efficacy in stratifying recurrence.Conclusion:The number of incorporating high-risk pathological features is an independent prognostic factor for RFS in patients with stage Ⅰ-ⅢCRC.Combining it as a multiclass variable with age,pT and pN stage has good prognostic stratification and recurrence stratification efficacy,which is expected to guide clinical treatment.

Background and purpose:Currently,for patients with mid-to-low locally advanced rectal cancer and potentially resectable T4bM0 colon cancer,guidelines recommend neoadjuvant therapy strategies to enhance the response rate and increase the likelihood of conversion surgery.Among these patients,ypⅢ stage colorectal cancer(CRC)is assessed using the Union for International Cancer Control(UICC)/American Joint Committee on Cancer(AJCC)TNM staging system for postoperative pathological features.However,neoadjuvant therapy can lead to lymph node regression in the surgical area,resulting in an insufficient number of detected lymph nodes(less than 12),preventing classification according to conventional TNM staging.Thus,TNM staging often fails to predict the prognosis of ypⅢ patients who have undergone neoadjuvant therapy.This study aimed to evaluate the prognostic value of the positive lymph node ratio(LNR)in ypⅢ stage CRC patients treated with neoadjuvant therapy.Methods:Retrospective data was collected from ypⅢ stage CRC patients who received neoadjuvant therapy and underwent radical surgery at Fudan University Shanghai Cancer Center between 2008 and 2018.Collect clinical pathological characteristics such as age,gender,primary tumor location,tumor differentiation grade,pathological staging,and whether the patient has relapsed or died during follow-up at the time of surgery.Inclusion criteria:CRC patients who have received neoadjuvant therapy and surgery and have been confirmed to be stage Ⅲ by postoperative pathological examination.Exclusion criteria:① Preoperative imaging examination or intraoperative exploration reveals distant organ metastasis;② History of malignant tumors in the past;③ Multiple primary CRC.This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(ethics number:050432-4-2108*).The R software survminer package(surv_cutpoint algorithm)was used to calculate the optimal cutoff value for LNR relative to disease-free survival(DFS),and patients were divided into low and high LNR groups accordingly.Clinical pathological characteristics and DFS were compared between the two groups.COX proportional hazards regression models were employed to identify adverse pathological features,and survival plots along with prediction models for DFS were generated using the survival and rms packages.Results:A total of 489 patients were included,comprising 289 males and 200 females,with a median age of 56 years(23-80 years)and a median follow-up time of 1 062 d.During the follow-up period,164 patients(33.5%)died.In the entire cohort,204(41.7%)patients had fewer than 12 lymph nodes detected.The optimal cutoff value for LNR was 0.29,classifying 317 patients into the low LNR group(LNR≤0.29)and 172 patients into the high LNR group(LNR＞0.29).The high LNR group exhibited shorter DFS compared to the low LNR group[hazard ratio(HR)=2.103,95%CI:1.582-2.796,P＜0.000 1].Multivariate COX regression indicated that LNR was an independent prognostic factor for DFS(HR=1.825,95%CI:1.391-2.394,P＜0.001).The inclusion of LNR in a multicategory DFS nomogram prediction model effectively assessed DFS in stage Ⅲ CRC patients who had undergone neoadjuvant therapy.Conclusion:LNR is an independent prognostic factor for ypⅢ stage CRC patients,showing good predictive power for DFS when combined with other adverse pathological features.Therefore,incorporating LNR as a supplement to TNM staging can improve the accuracy of CRC prognosis assessment.

Objective:To evaluate the endometrial implantation window in patients with recurrent implantation failure using endometrial receptive array(ERA)sequencing or endometrial histological detection methods,and to explore the effectiveness and cost-effectiveness analysis of two technologies for improving clinical outcomes in such patients.Methods:A retrospective cohort study was conducted on clinical data of 125 patients diagnosed with repeated implantation failure in Gansu Maternal and Child Health Hospital from January 2018 to December 2022.According to whether endometrial receptivity testing was accepted and different detection techniques were used,they were divided into a control group(n=36),a genomic group(n=35),and a histological group(n=54).The clinical data and pregnancy outcomes of the three groups were compared.Results:①The results of one-way ANOVA showed that the embryo implantation rate in the genomic group and histological group was significantly higher than that in the control group,and the difference was statistically significant(P＜0.05).There was no sta-tistically significant difference in embryo implantation rate between genomic and histological groups(P=0.48).②There was no statistically significant difference in clinical pregnancy rate and live birth rate among the three groups(P＞0.05).③Log rank test showed:The time for 50％of patients to reach live labor was significantly shorter than that of the control group,and the difference was statistically significant(P＜0.05);There was no sta-tistically significant difference in the time to live birth in 50％of patients between the genomic and histological groups of 50％of patients(P＞0.05).④The average number of embryos transferred in the control group was significantly higher than that in the genomic and histological groups,with statistical significance(P＜0.05).The cost of genomic patients was significantly higher than that of histology group,and the difference was statistically significant(P＜0.05).Conclusions:①Endometrial implantation window detection is feasible for patients with re-peated implantation failure,which can effectively shorten the time to live birth and reduce the number of transplan-ted embryos;②Both ERA sequencing and endometrial histology detection have limitations as methods to evaluate endometrial implantation window,and it is not clear which detection method has more advantages in accuracy and practicability.

Objective:To evaluate the endometrial implantation window in patients with recurrent implantation failure using endometrial receptive array(ERA)sequencing or endometrial histological detection methods,and to explore the effectiveness and cost-effectiveness analysis of two technologies for improving clinical outcomes in such patients.Methods:A retrospective cohort study was conducted on clinical data of 125 patients diagnosed with repeated implantation failure in Gansu Maternal and Child Health Hospital from January 2018 to December 2022.According to whether endometrial receptivity testing was accepted and different detection techniques were used,they were divided into a control group(n=36),a genomic group(n=35),and a histological group(n=54).The clinical data and pregnancy outcomes of the three groups were compared.Results:①The results of one-way ANOVA showed that the embryo implantation rate in the genomic group and histological group was significantly higher than that in the control group,and the difference was statistically significant(P＜0.05).There was no sta-tistically significant difference in embryo implantation rate between genomic and histological groups(P=0.48).②There was no statistically significant difference in clinical pregnancy rate and live birth rate among the three groups(P＞0.05).③Log rank test showed:The time for 50％of patients to reach live labor was significantly shorter than that of the control group,and the difference was statistically significant(P＜0.05);There was no sta-tistically significant difference in the time to live birth in 50％of patients between the genomic and histological groups of 50％of patients(P＞0.05).④The average number of embryos transferred in the control group was significantly higher than that in the genomic and histological groups,with statistical significance(P＜0.05).The cost of genomic patients was significantly higher than that of histology group,and the difference was statistically significant(P＜0.05).Conclusions:①Endometrial implantation window detection is feasible for patients with re-peated implantation failure,which can effectively shorten the time to live birth and reduce the number of transplan-ted embryos;②Both ERA sequencing and endometrial histology detection have limitations as methods to evaluate endometrial implantation window,and it is not clear which detection method has more advantages in accuracy and practicability.

Objective:To evaluate the endometrial implantation window in patients with recurrent implantation failure using endometrial receptive array(ERA)sequencing or endometrial histological detection methods,and to explore the effectiveness and cost-effectiveness analysis of two technologies for improving clinical outcomes in such patients.Methods:A retrospective cohort study was conducted on clinical data of 125 patients diagnosed with repeated implantation failure in Gansu Maternal and Child Health Hospital from January 2018 to December 2022.According to whether endometrial receptivity testing was accepted and different detection techniques were used,they were divided into a control group(n=36),a genomic group(n=35),and a histological group(n=54).The clinical data and pregnancy outcomes of the three groups were compared.Results:①The results of one-way ANOVA showed that the embryo implantation rate in the genomic group and histological group was significantly higher than that in the control group,and the difference was statistically significant(P＜0.05).There was no sta-tistically significant difference in embryo implantation rate between genomic and histological groups(P=0.48).②There was no statistically significant difference in clinical pregnancy rate and live birth rate among the three groups(P＞0.05).③Log rank test showed:The time for 50％of patients to reach live labor was significantly shorter than that of the control group,and the difference was statistically significant(P＜0.05);There was no sta-tistically significant difference in the time to live birth in 50％of patients between the genomic and histological groups of 50％of patients(P＞0.05).④The average number of embryos transferred in the control group was significantly higher than that in the genomic and histological groups,with statistical significance(P＜0.05).The cost of genomic patients was significantly higher than that of histology group,and the difference was statistically significant(P＜0.05).Conclusions:①Endometrial implantation window detection is feasible for patients with re-peated implantation failure,which can effectively shorten the time to live birth and reduce the number of transplan-ted embryos;②Both ERA sequencing and endometrial histology detection have limitations as methods to evaluate endometrial implantation window,and it is not clear which detection method has more advantages in accuracy and practicability.