Objective To systematically identify the key genes regulating the exit from na?ve pluripotency in embryonic stem cells(ESCs)in order to provide novel targets and theoretical insights into the mechanisms for pluripotency transition and early cell fate determination.Methods Nanog-green fluorescent protein(Nanog-GFP)reporter-labeled ESCs were infected with a genome-wide Brie knockout library,and further cultured under leukemia inhibitory factor/serum(LIF/S)conditions for 14 d.Flow cytometry was used to sort Nanog-GFP?(na?ve-state)and Nanog-GFP-(primed state)cell populations,followed by genomic DNA extraction and high-throughput sequencing.Model-based Analysis of Genome-wide CRISPR/Cas9 Knockout(MAGeCK)was applied to identify differential genes between GFP?/Input,GFP?/Input,and GFP?/GFP? groups.Metascape and Gene Set Enrichment Analysis(GSEA)were conducted for functional enrichment analysis.Then the obtained candidate genes were employed to construct knockout models,and their roles were assessed through cell morphology observation,Nanog-positive rate detection,colony formation assays,and pluripotency gene expression analysis.Results The GFP?/Input screening revealed 2 921 negatively regulated genes(mainly enriched in basic life processes,such as RNA metabolism and cell cycle)and 1 393 positively regulated genes(enriched in the processes of nervous system development,carbohydrate metabolism,and vascular system development).In the GFP?/Input screening,2 765 negatively regulated genes(enriched in RNA metabolism,cell cycle,and other fundamental processes)and 1 303 positively regulated genes(enriched in neural development,cell survival,and endothelial migration)were identified.The GFP?/GFP? comparison identified 1 001 negatively regulated genes[involved in stress response and inhibition of mitogen-activated protein kinase(MAPK)signaling]and 983 positively regulated genes[related to fibroblast growth factor/extracellular signal-regulated kinase(FGF/ERK)signaling pathway and glucose metabolism).These genes,were not only known pluripotency regulators(e.g.,Nanog,Nr5a2,Klf2,Klf4)and exit-associated genes(e.g.,Gata6,Grb2,Zeb1,Fgfr1),but also some novel candidates(e.g.,Dmrt1,Rxra,Zbtb14 and Tmem41b).Functional validation showed that transient knockout of Dmrt1,Tmem41b,and Hic2 significantly increased the proportion of Nanog? cells(P<0.01),suggesting their role in suppressing ground-state exit.ESCs with stable Dmrt1 knockout exhibited a more na?ve-state phenotype,presenting compact,dome-shaped colonies,with increased ratio of undifferentiated colonies(P<0.01),up-regulation of ground-state markers(Nanog,Nr5a2,Dppa3,P<0.01),and down-regulation of primed-state markers(Fgf5,Lefty1,Dnmt3b,P<0.01).Rescue experiments for Dmrt1 expression reversed these above phenotypes.Conclusion A candidate gene set regulating exit from na?ve pluripotency in ESC is screened out and identified with genome-wide CRISPR.Our findings implicate Dmrt1 plays a critical role in promoting the exit.

Objective To investigate the diagnostic value of serum silent information regulator factor 2-re-lated enzyme 1(SIRT1)and histone deacetylase 4(HDAC4)levels in sepsis complicated with acute kidney in-jury(AKI).Methods From January 2019 to December 2023,120 patients with sepsis complicated with AKI(AKI group)and 60 patients with simple sepsis(non-AKI group)were selected as the study objects.Clinical data of the two groups were collected,and serum SIRT1 and HDAC4 levels were detected by enzyme-linked immunosorbent assay.With sepsis complicated with AKI as the dependent variable,multivariate Logistic re-gression was used to analyze the influencing factors,and receiver operating characteristic(ROC)curve was drawn to evaluate the diagnostic efficacy of serum SIRT1 and HDAC4 levels in sepsis complicated with AKI.Results Compared with non-AKI group,serum SIRT1 level was decreased and HDAC4 level was increased in AKI group,the differences were statistically significant(P＜0.05).Compared with non-AKI group,the pro-portion of septic shock,kidney replacement therapy,sequential organ failure assessment(SOFA)score and se-rum creatinine level in AKI group were higher,and the differences were statistically significant(P＜0.05).Multivariate Logistic regression analysis showed that the independent risk factors of sepsis complicated with AKI were septic shock,increased SOFA score,increased serum creatinine and increased HDAC4(P＜0.05),and the independent protective factor was increased SIRT1(P＜0.05).ROC curve analysis results showed that the area under the curve(AUC)of serum SIRT1 and HDAC4 combined diagnosis of sepsis complicated with AKI was 0.891,which was larger than the AUC of serum SIRT1 and HDAC4 alone diagnosis(Z=3.681,3.081,P＜0.001,P=0.002).Conclusion The decrease of serum SIRT1 level and the increase of HDAC4 level are related to sepsis complicated with AKI,and the combination of serum SIRT1 and HDAC4 level has high diagnostic value.

Inflammatory bowel disease (IBD) is an autoimmune disorder involving complex immune regulation, where balancing localized and systemic immunosuppression is a key challenge. This study aimed to enhance the therapeutic efficacy by engineering the probiotic Escherichia coli Nissle 1917 (EcN). We removed endogenous plasmids pMUT1 and pMUT2 from wild-type EcN and expressed the mPD-L1 (19‒238 aa)-mFc fusion protein on the bacterial surface using a cytolysin A (ClyA) fragment. This modification stabilized mPD-L1 (19‒238 aa) protein expression and promoted its recruitment to outer membrane vesicles (OMVs). The engineered strain, EcNΔ_pMUT1/2-ClyA-mPD-L1-mFc (EcN-ePD-L1-mFc), features conditional ePD-L1-mFc expression under the araBAD promoter, enhancing gut-targeted release and reducing systemic side effects. This strain improved treatment targeting and efficiency by enabling direct ePD-L1-mFc interaction with immune cells at inflammation sites. OMVs from this strain induced Treg proliferation, inhibited effector T cell proliferation in vitro, and significantly improved intestinal inflammation and colonic epithelial barrier repair in vivo. Additionally, the bacterium restored intestinal microbiota balance, increasing Lactobacillaceae and reducing Bacteroides. This study highlights the engineered bacterium's potential for targeted intestinal immune modulation and offers a novel local IBD treatment approach with promising clinical prospects.

We retrospectively analyzed 8 patients who had been on hemodialysis for over 30 years from two dialysis centers in Dalian, China. A literature review was conducted by searching PubMed, CNKI, Wanfang databases,and Chinese Medical Journal Network for cases of patients on hemodialysis for over 30 years. The 8 patients had good baseline health, with chronic glomerulonephritis as the primary renal disease and no comorbidities before initiating dialysis. They started hemodialysis between 21 and 38 years of age, predominantly using arteriovenous fistulas for vascular access. Dialysis was regular and adequate (KT/V 1.23-1.88). Key laboratory parameters, including hemoglobin (88-118 g/L), albumin (27.7-39.7 g/L), calcium (1.88-2.55 mmol/L), and phosphate (0.76-1.99 mmol/L), were generally within target ranges. Body mass index ranged from 15.20 to 22.96 kg/m2. This literature review of the study included 12 case reports and 4 orginal articles. Factors influencing long-term survival included baseline health status, primary renal disease, absence of comorbidities before dialysis initiation, age at dialysis initiation, type of vascular access, dialysis adequacy, complication management, and medical support. Standardized management and timely correction of complications can significantly improve prognosis and enhance long-term survival in hemodialysis patients.

Objective:To analyze the correlation between mental health status and metabolic syndrome (MetS) in health checkup people.Methods:It was a cross-sectional study, 2 920 participants who received health checkup in the Health Examination Center of Peking University Third Hospital from January 2019 to December 2023 were selected using cluster sampling method. Their general information, physical examination, biochemical indicators, body composition, and self-evaluation scores on the Symptom Checklist-90 (SCL-90) were collected. According to the inclusion and exclusion criteria, a total of 2 813 study subjects were included, and divided into the MetS group and the non-MetS group based on whether they had MetS. The differences in general demographic information, body composition, blood biochemistry, and SCL-90 scores between the two groups were compared. Binary Logistic regression analysis was used to explore the correlation between mental health status and MetS.Results:Of the 2 813 subjects included, 1 576 were males (56.0%) and 1 237 were females (44.0%), with an average age of (41.7±11.0) years, the MetS group had 586 cases (20.8%) and the non-MetS group had 2 227 cases (79.2%). The MetS group had higher levels of age, body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, total cholesterol, triglycerides, low density lipoprotein cholesterol (LDL-C), fasting blood glucose, glycosylated hemoglobin (HbA 1c), free thyroxine(FT4), total triiodothyronine (TT3), free triiodothyronine (FT3), waist-to-hip ratio, visceral fat area, body fat percentage, uric acid/creatinine, homocysteine (Hcy), aspartate aminotransferases (AST), and alanine transaminase (ALT) levels, as well as higher scores for somatization, hostility, paranoia, and other factor compared to the non-MetS group (all P<0.05), while high density lipoprotein cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR) levels were lower than those in the non-MetS group (all P<0.05). The proportion of male, and the positive rates of SCL-90, somatization, interpersonal sensitivity, hostility, paranoia and other factor in the MetS group were higher than those in the non-MetS group (all P<0.05). Multifactorial analysis showed that individuals with a positive SCL-90 assessment had a 1.34 times higher risk of MetS than those with a negative assessment ( OR=1.34, 95% CI: 1.06-1.68; P=0.014). Among them, individuals with positive somatization ( OR=2.02, 95% CI: 1.25-3.28; P=0.004) and hostility ( OR=1.61, 95% CI: 1.02-2.56; P=0.042) had increased risk of MetS. Conclusion:Poor mental health status increases the risk of MetS.

Objective:To assess the impact of induction chemotherapy sensitivity on the prognosis and larynx preservation rates in patients with locally advanced hypopharyngeal cancer and to identify risk factors influencing induction chemotherapy sensitivity.Methods:This study included patients with locally advanced (stage III-IV) hypopharyngeal cancer who received induction chemotherapy as initial treatment at the Eye & ENT Hospital of Fudan University between August 2017 and September 2022. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, enrolled patients were classified into the sensitive group and the resistant group according to their response to induction chemotherapy. Chi-square tests and Log-rank tests were used to compare the objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and laryngeal preservation rate (LPR) between groups. Propensity score matching (PSM) was employed to accurately evaluate the impact of induction chemotherapy sensitivity on prognosis in real-world settings. Univariate and multivariate logistic regression analyses were performed to identify risk factors for induction chemotherapy resistance in locally advanced hypopharyngeal cancer.Results:A total of 197 patients with locally advanced hypopharyngeal cancer who received induction chemotherapy as initial treatment were included in, comprising 195 males and 2 females, with ages ranging from 36 to 74 years. Among them, 155 patients (78.68%) were classified into the sensitive group and 42 patients (21.32%) into the resistant group. The overall response rate (ORR) of induction chemotherapy in this cohort was 78.68%, with a five-year OS rate of 63.7%. The sensitive group had significantly better OS (mOS 6.32 vs. 5.05 year), PFS (mPFS 5.71 vs. 3.09 year) and a significantly higher LPR (91.6% vs. 69.0%) ( P<0.05). After propensity score matching, all covariates were balanced between the two groups, and the sensitive group showed significant improvement in OS ( P<0.05), while, no significant difference was observed in PFS and LPR between the two groups. Logistic regression analysis revealed that risk factors for induction chemotherapy failure in locally advanced hypopharyngeal cancer included: smoking status ( OR [95% CI]=4.751 [1.887-11.961]), tumor location in the posterior pharyngeal wall ( OR [95% CI]=2.988 [1.264-7.063]), and cN2-3 stage ( OR [95% CI]=3.641 [1.109-11.954]) ( P<0.05). Conclusions:Induction chemotherapy sensitivity significantly affects the prognosis of locally advanced hypopharyngeal cancer, which is influenced by various risk factors, including smoking status, tumor sublocation, and clinical N stage.

We retrospectively analyzed 8 patients who had been on hemodialysis for over 30 years from two dialysis centers in Dalian, China. A literature review was conducted by searching PubMed, CNKI, Wanfang databases,and Chinese Medical Journal Network for cases of patients on hemodialysis for over 30 years. The 8 patients had good baseline health, with chronic glomerulonephritis as the primary renal disease and no comorbidities before initiating dialysis. They started hemodialysis between 21 and 38 years of age, predominantly using arteriovenous fistulas for vascular access. Dialysis was regular and adequate (KT/V 1.23-1.88). Key laboratory parameters, including hemoglobin (88-118 g/L), albumin (27.7-39.7 g/L), calcium (1.88-2.55 mmol/L), and phosphate (0.76-1.99 mmol/L), were generally within target ranges. Body mass index ranged from 15.20 to 22.96 kg/m2. This literature review of the study included 12 case reports and 4 orginal articles. Factors influencing long-term survival included baseline health status, primary renal disease, absence of comorbidities before dialysis initiation, age at dialysis initiation, type of vascular access, dialysis adequacy, complication management, and medical support. Standardized management and timely correction of complications can significantly improve prognosis and enhance long-term survival in hemodialysis patients.

Objective:To analyze the correlation between mental health status and metabolic syndrome (MetS) in health checkup people.Methods:It was a cross-sectional study, 2 920 participants who received health checkup in the Health Examination Center of Peking University Third Hospital from January 2019 to December 2023 were selected using cluster sampling method. Their general information, physical examination, biochemical indicators, body composition, and self-evaluation scores on the Symptom Checklist-90 (SCL-90) were collected. According to the inclusion and exclusion criteria, a total of 2 813 study subjects were included, and divided into the MetS group and the non-MetS group based on whether they had MetS. The differences in general demographic information, body composition, blood biochemistry, and SCL-90 scores between the two groups were compared. Binary Logistic regression analysis was used to explore the correlation between mental health status and MetS.Results:Of the 2 813 subjects included, 1 576 were males (56.0%) and 1 237 were females (44.0%), with an average age of (41.7±11.0) years, the MetS group had 586 cases (20.8%) and the non-MetS group had 2 227 cases (79.2%). The MetS group had higher levels of age, body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, total cholesterol, triglycerides, low density lipoprotein cholesterol (LDL-C), fasting blood glucose, glycosylated hemoglobin (HbA 1c), free thyroxine(FT4), total triiodothyronine (TT3), free triiodothyronine (FT3), waist-to-hip ratio, visceral fat area, body fat percentage, uric acid/creatinine, homocysteine (Hcy), aspartate aminotransferases (AST), and alanine transaminase (ALT) levels, as well as higher scores for somatization, hostility, paranoia, and other factor compared to the non-MetS group (all P<0.05), while high density lipoprotein cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR) levels were lower than those in the non-MetS group (all P<0.05). The proportion of male, and the positive rates of SCL-90, somatization, interpersonal sensitivity, hostility, paranoia and other factor in the MetS group were higher than those in the non-MetS group (all P<0.05). Multifactorial analysis showed that individuals with a positive SCL-90 assessment had a 1.34 times higher risk of MetS than those with a negative assessment ( OR=1.34, 95% CI: 1.06-1.68; P=0.014). Among them, individuals with positive somatization ( OR=2.02, 95% CI: 1.25-3.28; P=0.004) and hostility ( OR=1.61, 95% CI: 1.02-2.56; P=0.042) had increased risk of MetS. Conclusion:Poor mental health status increases the risk of MetS.

Objective To establish a model that integrates ultrasound features and immunological characteristics for predicting the efficacy of neoadjuvant chemotherapy(NAC)in breast cancer patients.Methods A total of 203 breast cancer patients undergoing preoperative NAC at the Fifth Medical Center of the PLA General Hospital between July 2021 and July 2024 were screened.In line with the inclusion/exclusion criteria,177 patients were included.Data on ultrasound and immunohistochemistry was collected.These patients were divided into pathological complete response(pCR)and non-pathological complete response(non-pCR)groups based on postoperative pathology.Factors with P＜0.0 1 in univariate analysis were evaluated using multivariate Logistic regression.Independent predictive factors were used to construct and validate the ultrasound-immunohistochemical model via Bootstrap.Results The reduction rateof the maximum diameter of lesions,posterior echo attenuation,PR status and HER-2 status were identified as independent predictors of pCR(all P＜0.05).The model proved to be highly accurate and stable.Conclusion The model that combines ultrasound and immunohistochemical features can effectively evaluatep CR after NAC in breast cancer patients.

Objective:To assess the impact of induction chemotherapy sensitivity on the prognosis and larynx preservation rates in patients with locally advanced hypopharyngeal cancer and to identify risk factors influencing induction chemotherapy sensitivity.Methods:This study included patients with locally advanced (stage III-IV) hypopharyngeal cancer who received induction chemotherapy as initial treatment at the Eye & ENT Hospital of Fudan University between August 2017 and September 2022. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, enrolled patients were classified into the sensitive group and the resistant group according to their response to induction chemotherapy. Chi-square tests and Log-rank tests were used to compare the objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and laryngeal preservation rate (LPR) between groups. Propensity score matching (PSM) was employed to accurately evaluate the impact of induction chemotherapy sensitivity on prognosis in real-world settings. Univariate and multivariate logistic regression analyses were performed to identify risk factors for induction chemotherapy resistance in locally advanced hypopharyngeal cancer.Results:A total of 197 patients with locally advanced hypopharyngeal cancer who received induction chemotherapy as initial treatment were included in, comprising 195 males and 2 females, with ages ranging from 36 to 74 years. Among them, 155 patients (78.68%) were classified into the sensitive group and 42 patients (21.32%) into the resistant group. The overall response rate (ORR) of induction chemotherapy in this cohort was 78.68%, with a five-year OS rate of 63.7%. The sensitive group had significantly better OS (mOS 6.32 vs. 5.05 year), PFS (mPFS 5.71 vs. 3.09 year) and a significantly higher LPR (91.6% vs. 69.0%) ( P<0.05). After propensity score matching, all covariates were balanced between the two groups, and the sensitive group showed significant improvement in OS ( P<0.05), while, no significant difference was observed in PFS and LPR between the two groups. Logistic regression analysis revealed that risk factors for induction chemotherapy failure in locally advanced hypopharyngeal cancer included: smoking status ( OR [95% CI]=4.751 [1.887-11.961]), tumor location in the posterior pharyngeal wall ( OR [95% CI]=2.988 [1.264-7.063]), and cN2-3 stage ( OR [95% CI]=3.641 [1.109-11.954]) ( P<0.05). Conclusions:Induction chemotherapy sensitivity significantly affects the prognosis of locally advanced hypopharyngeal cancer, which is influenced by various risk factors, including smoking status, tumor sublocation, and clinical N stage.