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Background: One of the features of tumor immunity is the immunosuppressive tumor microenvironment (TME). In this study, TME gene signatures were used to define the characteristics of Cervical squamous cell carcinoma (CESC) immune subtypes and construct a new prognostic model.Methods: Single sample gene set enrichment analysis (ssGSEA) was used to quantify pathway activity. RNA-seq of 291 CESC were obtained from the Cancer Genome Atlas (TCGA) database as a training set. Microarray-based data of 400 cases of CESC were obtained from the Gene Expression Compilation (GEO) database as an independent validation set. 29 TME related gene signatures were consulted from previous study. Consensus Cluster Plus was employed to identify molecular subtype. Univariate cox regression analysis and random survival forest (RSF) were used to establish the immune-related gene risk model based on the TCGA data set of CESC, and the accuracy of prognosis prediction was verified by GEO data set. ESTIMATE algorithm was used to perform immune and matrix scores on the data set.Results: three molecular subtypes (C1, C2, C3) were screened in TCGA-CESC on account of 29 TME gene signatures. Among, C3 with better survival outcome had higher immune related gene signatures, while C1 with worse prognosis time had enhanced matrix related features. Increased immune infiltration, inhibition of tumor related pathways, widespread genomic mutations and prone immunotherapy were observed in C3. Furthermore, a five immune genes signature was constructed and predicted overall survival for CESC, which successfully validated in GSE44001 dataset. A positive phenomenon was observed between five hub genes expressions and methylation. Similarly, high group enriched in matrix related features, while immune related gene signatures were enriched in low group. Immune cell, immune checkpoints genes expression levels were negatively, while most TME gene signatures were positively correlated with Risk Score. In addition, high group was more sensitive to drug resistance.Conclusion: This work identified three distinct immune subtypes and a five genes signature for predicting prognosis in CESC patients, which provided a promising treatment strategy for CESC.

BackgroundSmall cell carcinoma of ovary (SCCO) is a rare and aggressive cancer primarily reported in the form of case reports. Due to limited epidemiological and prognostic analyses based on large populations, SCCO has varied considerably without prognostic models and a recognized first-line treatment strategy. The study aimed to compare the clinical characteristics, treatment methods, and prognosis of SCCO and high-grade serous ovarian cancer (HGSOC), the most prevalent subtype of ovarian cancer, in a large sample and develop a predictive model for these two subtypes.MethodsData from the Surveillance, Epidemiology, and End Results program were analyzed for patients with SCCO or HGSOC from 2000 to 2017. Clinical, demographic, and treatment characteristics were compared between the two groups. Propensity-score matching, Cox risk regression analysis, and Kaplan-Meier survival curves were used to assess the data. Finally, a nomogram was developed to predict the patient survival time.ResultsA total of 32,185 women, including 31,979 (99.4%) diagnosed with HGSOC and 206 (0.6%) diagnosed with SCCO, were identified. Age ≤ 51 years, single, median house income less than $70,000, early stage, and unilateral disease were more common characteristics of patients with SCCO than those with HGSOC. Patients with SCCO were more likely to receive radiotherapy (6.8% vs. 0.8%, p

BackgroundOver the last 2 decades, patients with low rectal cancer have had better outcomes from improvements in surgical techniques in sphincter preservation. We aimed to quantify the trends in sphincter-preserving surgeries for low rectal cancer over 20 years in a top tertiary hospital in China.MethodsBetween 1999 and 2021, a cohort of patients with primary malignant rectal tumor ≤5cm from the anal verge and who received elective surgeries at Changhai Hospital, Shanghai, China, was identified. Data were extracted from electronic medical records. A Joinpoint Regression Model was used to analyze trends in surgical procedures by average annual percentage change (AAPC). Adjusted Cox proportional hazards regression model was used to assess overall survival.ResultsAmong a total of 4,172 patients during the study period, 3,111 (74.6%) underwent a sphincter-preserving surgery and 1,061 (25.4%) received APR. Sphincter-preserving surgery increased 3.6% per year (95%CI, 2.3-4.9). Low anterior resection was the most performed procedure (86.3%) and maintained a steady trend, while intersphincteric resection increased 49.4% annually (95%CI, 19.5-86.7) after initiation. Laparoscopic techniques increased 15.1% per year (95%CI, 8.4-43.4) after initiation. Sphincter-preserving surgery increased annually for tumors ≤2cm, 2-≤3cm and 3-≤4cm from the anal verge (AAPC 7.1, 4.5-9.8; 4.7, 3.1-6.3; 2.7, 1.7-3.6, respectively). Furthermore, patients with sphincter-preserving surgery had a better overall survival than abdominoperineal resection (APR) patients (adjusted HR 0.78, 95% CI, 0.65-0.93, p=.01).ConclusionsUtilization of sphincter-preserving surgeries increased significantly over the last 20 years. Patients with low rectal cancer who underwent sphincter preservation had better survival than similar patients who underwent APR.

Background: Antidepressant (AD) algorithm is an important tool to support treatment decision-making and improve management of major depressive disorder (MDD). However, little is known about its concordance with real-world practice. This study aimed to assess the concordance between the longitudinal treatment patterns and AD algorithm recommended by a clinical practice guideline in China.Methods: Data were obtained from the electronic medical records of Shanghai Mental Health Center (SMHC), one of the largest mental health institutions in China. We examined the concordance between clinical practice and the Canadian Network for Mood and Anxiety Treatments (CANMAT) algorithm among a cohort composed of 19,955 MDD patients. The longitudinal characteristics of treatment regimen and duration were described to identify the specific inconsistencies. Demographics and health utilizations of the algorithm-concordant and -discordant subgroups with optimized treatment were measured separately.Results: The overall proportion of algorithm-concordant treatment significantly increased from 84.45% to 86.03% during the year of 2015–2017. Among the patients who received recommended first-line drugs with subsequent optimized treatment (n = 2977), the concordance proportion was 27.24%. Mirtazapine and trazodone were the most used drugs for adjunctive strategy. Inadequate or extended duration before optimized treatment are common inconsistency. The median length of follow-up for algorithm-concordant (n = 811) and algorithm-discordant patients (n = 2166) were 153 days (Q1-Q3 = 79–328) and 368 days (Q1-Q3 = 181–577) respectively, and the average number of clinical visits per person-year was 13.07 and 13.08 respectively.Conclusion: Gap existed between clinical practice and AD algorithm. Improved access to evidence-based treatment is required, especially for optimized strategies during outpatient follow-up.

ObjectivesAlanine aminotransferase (ALT) level is one of the crucial indexes to evaluate disease status for chronic hepatitis B (CHB) patients. However, whether the ALT level after nucleos(t)ide analog (NA) treatment is associated with hepatocellular carcinoma (HCC) development remains unclear.Materials and MethodsWe evaluated the association between ALT level and HCC occurrence in NA-treated patients and investigated the predictive value of ALT flare for HCC. The associations between ALT level and HCC were analyzed by logistic regression and Cox proportional hazards models.ResultsThere were 21,223 CHB patients at Ruijin Hospital of China and 16,737 CHB patients in the Optum electronic health records (EHR) in the United States (US) treated with NAs between 2010 and 2018. Among them, 8,152 and 4,893 patients who achieved a normal ALT value were included in the study cohorts, respectively. A significant positive dose-dependent correlation between the peak ALT level and HCC was identified in both cohorts. Within the China cohort, ALT flare was significantly associated with increased risks of HCC compared to normal ALT (HR 2.55, 95%CI 1.45–4.50). Stronger increased risks associated with ALT flare were observed in the US cohort (HR 7.62, 95%CI 4.85–11.98).ConclusionsALT flare is a strong predictor for HCC occurrence in the CHB patients treated with NAs. Elevation of ALT, especially ALT flare warrants close monitoring for early HCC detection.