Neoadjuvant therapy has become the standard treatment for locally advanced resectable esophageal cancer, significantly improving long-term survival compared to surgery alone. Neoadjuvant therapy has evolved to include various strategies, such as concurrent chemoradiotherapy, chemotherapy, immunotherapy, or targeted combination therapy. This enriches clinical treatment options and provides a more personalized and scientific treatment approach for patients. This article aims to comprehensively summarize current academic research hot topics, review the rationale and evaluation measures of neoadjuvant therapy, discuss challenges in restaging methods after neoadjuvant therapy, and identify the advantages and disadvantages of various neoadjuvant therapeutic strategies.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Objective:To investigate the current application of blood purification in the treatment of acute poisoning within Jiangsu Province and to evaluate the impact of extracorporeal blood purification on the clinical outcomes of critically poisoned patients.Methods:This multicenter, cross-sectional real-world observational study followed patients presenting with poisoning to the emergency departments of nine hospitals in Jiangsu Province between June 2015 and May 2019. Data were collected on demographic characteristics, vital signs within the first hour of emergency presentation, treatment modalities, length of hospital stay, and survival outcomes. Clinical data from patients who underwent extracorporeal blood purification were compared with those who did not, using the Wilcoxon rank-sum test and Chi-square test.Results:A total of 4 178 poisoning cases were included between June 2015 and May 2019. Among them, 21.7% (908/4 178) received blood purification therapy, while 78.3% (3 270/4 178) did not. Hemoperfusion (90.4%) was the most frequently employed method, followed by continuous renal replacement therapy (CRRT) (4.4%). In combined blood purification modalities, 4.8% underwent hemoperfusion combined with CRRT, 0.1% received hemoperfusion with plasma exchange, and another 0.1% underwent hemoperfusion combined with both CRRT and plasma exchange. Among patients who underwent blood purification, pesticide poisoning was the most prevalent (76.3%), with the most common toxic agents being paraquat (23.7%), dichlorvos (8.7%), methamidophos (5.2%), omethoate (4.0%), and glyphosate (3.7%). Compared to the non-blood purification group, patients in the blood purification group were more likely to present within the first hour with a low Glasgow Coma Scale (GCS) score (3-8) (22.6% vs. 9.7%, P <0.05), low mean arterial pressure (8.0% vs. 3.2%, P <0.05), longer hospital stays [5(3,9) days vs. 2(1,4) days, P <0.05] and a higher in-hospital mortality rate (21.1% vs. 5.3%, P <0.05). Follow-up via telephone 28 days after discharge revealed a survival rate of 78.9%, with a mortality rate of 21.1% in the blood purification group. Conclusions:Hemoperfusion is the most commonly utilized blood purification technique for treating poisoning in Jiangsu Province, with pesticides being the primary toxic agents treated. Although the mortality rate is higher in the blood purification group, the intervention may still contribute to improved patient outcomes.

Objective:To investigate the genetic subtypes and drug resistance monitoring of newly reported human immunodeficiency virus (HIV) infection/AIDS virus in Anhui Province from 2020 to 2023.Methods:An observational design study was used to collect blood samples from patients diagnosed with HIV/AIDS in the AIDS Prevention and Control Department of Anhui Provincial Center for Disease Control and Prevention from January 2020 to December 2023.The HIV-1 pol gene was amplified by reverse transcription-nested PCR, and the genetic subtypes were identified by phylogenetic tree analysis using MEGA 7.0 software. The mutation sites of drug resistance were analyzed by the online software tool of Stanford University′s HIV Drug resistance database. The influencing factors of drug resistance before treatment were analyzed by multivariate logistic analysis.Results:A total of 335 plasma samples were collected, and 332 HIV-1 pol gene sequences were obtained successfully. The main gene subtypes were CRF01-AE, accounting for 35.55% (118/332), followed by CRF07-BC, B and B+C types [29.22% (97/332), 11.74% (39/332), 9.93% (33/332)]. The total drug resistance rate before treatment was 30.12%(32/100), and the drug resistance rate of protease inhibitor (PIs) in HIV-1 was 6.33% (21/332). The drug resistance rate of nucleoside reverse transcriptase inhibitors (NRTI) before treatment was 6.33% (21/332). The drug resistance rate of non-nucleoside reverse transcriptase inhibitors (NNRTI) before treatment was 17.47% (58/332).The comparison of drug resistance rate of different drug types showed statistical significance ( χ2=30.435, P<0.05).Among the 100 cases of drug resistance, the main mutation point of HIV-1 protease inhibitor was Q58E (21.00%), and the main mutation point of nucleoside reverse transcriptase inhibitor was M184V/I (6.00%). Non-nucleoside reverse transcriptase inhibitor resistance mutation points mainly K103N (22.00%).There were statistically significant differences in the starting time of antiviral therapy, the number of CD4 +T cells at baseline and the drug resistance rate of gene subtypes (the chi-square values are respectively 24.152, 32.516, 11.652, P<0.05).Multivariate logistic analysis showed that the baseline CD4 +T cell count was <200/μl, subtype B, subtype B+C, CRF01-AE subtype, CRF55-01B subtype and 01-BC subtype was the influential factor of drug resistance before treatment (the chi-square values are respectively 4.577, 8.202, 4.416, 5.206, 7.603 and 4.804, P<0.05). Conclusion:The newly reported HIV/AIDS population in Anhui Province from 2020 to 2023 has a variety of viral gene subtypes, and NNRTIs are the main types of drug resistance gene mutations before treatment. Attention should be paid to the number of baseline CD4 +T cells, the duration of antiviral treatment, and the distribution of gene subtypes to reduce the drug resistance of HIV/AIDS patients before treatment.

Objective This study aimed to explore the differences in global and local brain network topological properties between deficient pattern(DP)and excess pattern(EP)of mild vascular cognitive impairment caused by subcortical small vessel disease based on graph theory network.Methods Patients were recruited prospectively and were classified with DP and EP subtype.The global small-world topological attributes and local nodes were calculated for the comparison of DP,EP,and healthy controls(CN)using the GRETNA platform.Results The three groups all had small-world attributes,but only the patients in EP had a significantly lower small world attribute δ in the range of 0.05-0.26 than the control group(P<0.05).The node efficiency and node strength indicators of multiple brain region were able to significantly distinguish the DP group from the EP group.However,there was no positive brain region in the node efficiency of the DP patients(P>0.05),and only a few brain regions showed increased node strength efficiency(P<0.05).Conclusion The results indicate that the syndrome of DP and EP have significantly different neuroimaging phenotypes,providing a basis for further research of biological classification based on Chinese Medicine syndromes.

Objective:To explore the diagnostic value of serum cystatin C (CysC) and C1q tumor necrosis factor-related protein 9 (CTRP9) levels for diabetic retinopathy (DR) and diabetic macular edema (DME) in patients with type 2 diabetes.Methods:A cross-sectional study was conducted.A total of 135 patients with type 2 diabetes, aged 45-75 years, who were treated in Gansu Provincial Hospital from April 2021 to April 2022 were included.According to DR grading standard, patients were divided into non-DR (NDR) group, non-proliferative DR (NPDR) group and proliferative DR (PDR) group, with 45 patients in each group.The DR patients were subdivided into DME group (51 cases) and non-DME group (39 cases).A total of 45 healthy subjects were selected as the normal control group.Fasting peripheral venous blood was collected to detect serum glycosylated hemoglobin, fasting blood glucose, triacylglycerol, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, CysC and CTRP9 levels.The expression of CysC and CTRP9 levels among different groups were compared.The independent influencing factors of DR and DME were evaluated by multivariate logistic regression analysis model.The diagnostic value of serum CysC and CTRP9 in DR and DME were evaluated by receiver operating characteristic (ROC) curve.This study adhered to the Declaration of Helsinki and the study protocol was approved by the Ethics Committee of Gansu Provincial Hospital (No.2021-301).All patients were informed about the purpose and methods of the study and signed an informed consent form.Results:Serum CysC levels in normal control group, NDR group, NPDR group and PDR group were 0.74(0.67, 0.83), 1.03(0.85, 1.22), 1.40(0.98, 1.63) and 1.66(1.31, 1.85)mg/L, respectively, showing a gradually increasing trend, and the serum CTRP9 levels were (136.90±14.95), (120.23±16.31), (109.50±14.71) and (90.99±13.88)pg/ml, respectively, showing a gradually decreasing trend, with statistically significant overall comparison differences among groups ( Z=89.430, P<0.001; F=74.242, P<0.001), the comparison within groups was statistically significant (all at P<0.05).Compared with non-DME group, the serum CysC level was significantly increased and serum CTRP9 level was significantly decreased in DME group (both P<0.05).Multivariate logistic regression analysis showed that serum CysC (odds ratio [ OR]=19.742, 95% confidence interval [ CI]: 4.515-86.316, P<0.001) was the independent risk influencing factors for the occurrence of DR, and CTRP9 ( OR=0.937, 95% CI: 0.908-0.966, P<0.001) was a protective factor for the occurrence of DR.Serum CTRP9 level ( OR=0.838, 95% CI: 0.778-0.903, P<0.001) was a protective factor for DME.The ROC curve showed that the area under ROC curve (AUC) for serum CysC and CTRP9 levels alone and in combination for the diagnosis of DR in patients with type 2 diabetes mellitus complicated by DR were 0.798, 0.802 and 0.870, respectively.The cutoff values of serum CysC and CTRP9 levels to obtain the best diagnostic efficacy were 1.34 mg/L and 110.12 pg/ml, respectively.The AUC for serum CysC and CTRP9 level alone and in combination for the diagnosis of DME in DR patients were 0.682, 0.923 and 0.923, respectively.The cutoff value of serum CTRP9 level to obtain optimal diagnostic efficacy was 104.68 pg/ml. Conclusions:The enhanced expression of serum CysC level and reduced expression of serum CTRP9 level are the risk factors for the development of DR in type 2 diabetes patients.The decrease of serum CTRP9 level is one of the risk factors for the development of DME in DR patients.

Objective:To investigatethe heterogeneity of career growth recognition amongphysicians at the stage of standardized training and the growth characteristics of clinical physicians in the early stage, and to provide a reference for improving the quality of standardized training.Methods:The trainees who received standardized residency trainingwere randomly selected from three grade A tertiary hospitals in Chongqing, China. Mplus7.4 was used for latent profile analysis to explain the relationship between explicit continuous indicators, and the subtypes of career growth recognition were analyzed.Results:Career growth recognition at the stage of standardized training was classifiedinto three subtypes of all-round growth recognition, high resource and expectation recognition, and unclassified growth recognition, among which the subtype of unclassified growth recognition accounted for the highest percentage of 40.27% (207 trainees).Conclusions:Physicians at the stage of standardized training show obvious uncertainty aboutcareer growth recognition, and it is necessary to strengthen the education on career growth recognition during standardized training and design a development pathway based on the characteristics of career growth recognition.

Objective:To analyze immune reconstitution and influencing factors in HIV infected men who have sex with men (MSM) with access to antiviral therapy (ART) in Guangxi Zhuang Autonomous Region (Guangxi) during 2005-2021.Methods:The data were collected from Chinese Disease Prevention and Control Information System. The study subjects were HIV infected MSM with access to the initial ART for ≥24 weeks in Guangxi from 2005 to 2021 and HIV RNA lower than the detection limit within 24 months. The proportion of infected MSM who had immune reconstitution after ART was calculated. Cox proportional hazard regression model was used to analyze the influencing factors of immune reconstitution. Software SPSS 24.0 was used for statistical analysis.Results:A total of 3 200 HIV infected MSM were enrolled, in whom 15.56 % (498/3 200) had no immune reconstitution, 14.78% (473/3 200) had moderate immune reconstitution, and the rate of complete immune reconstitution was 69.66% (2 229/3 200). The M ( Q1, Q3) of ART time for immune reconstitution was 12 (5, 27) months. Multivariate Cox proportional risk regression model analysis results showed that compared with those with initial ART at age ≥30 years, WHO clinical stage Ⅲ/Ⅳ illness, baseline BMI <18.50 kg/m 2 and baseline CD4 +T lymphocyte (CD4) counts <200 cells/μl, HIV infected MSM with initial ART at age <30 years, WHO clinical stageⅠ/Ⅱ illness, baseline BMI≥24.00 kg/m 2 and baseline CD4 counts ≥200 cells/μl were more likely to have complete immune reconstitution. Conclusions:In the HIV infected MSM in Guangxi, failures to achieve moderate and complete immune reconstitution were observed. Surveillance and ART regimen should be improved for key populations, such as those with older age and low baseline CD4 counts.

Objective:To investigate the genetic subtypes and drug resistance monitoring of newly reported human immunodeficiency virus (HIV) infection/AIDS virus in Anhui Province from 2020 to 2023.Methods:An observational design study was used to collect blood samples from patients diagnosed with HIV/AIDS in the AIDS Prevention and Control Department of Anhui Provincial Center for Disease Control and Prevention from January 2020 to December 2023.The HIV-1 pol gene was amplified by reverse transcription-nested PCR, and the genetic subtypes were identified by phylogenetic tree analysis using MEGA 7.0 software. The mutation sites of drug resistance were analyzed by the online software tool of Stanford University′s HIV Drug resistance database. The influencing factors of drug resistance before treatment were analyzed by multivariate logistic analysis.Results:A total of 335 plasma samples were collected, and 332 HIV-1 pol gene sequences were obtained successfully. The main gene subtypes were CRF01-AE, accounting for 35.55% (118/332), followed by CRF07-BC, B and B+C types [29.22% (97/332), 11.74% (39/332), 9.93% (33/332)]. The total drug resistance rate before treatment was 30.12%(32/100), and the drug resistance rate of protease inhibitor (PIs) in HIV-1 was 6.33% (21/332). The drug resistance rate of nucleoside reverse transcriptase inhibitors (NRTI) before treatment was 6.33% (21/332). The drug resistance rate of non-nucleoside reverse transcriptase inhibitors (NNRTI) before treatment was 17.47% (58/332).The comparison of drug resistance rate of different drug types showed statistical significance ( χ2=30.435, P<0.05).Among the 100 cases of drug resistance, the main mutation point of HIV-1 protease inhibitor was Q58E (21.00%), and the main mutation point of nucleoside reverse transcriptase inhibitor was M184V/I (6.00%). Non-nucleoside reverse transcriptase inhibitor resistance mutation points mainly K103N (22.00%).There were statistically significant differences in the starting time of antiviral therapy, the number of CD4 +T cells at baseline and the drug resistance rate of gene subtypes (the chi-square values are respectively 24.152, 32.516, 11.652, P<0.05).Multivariate logistic analysis showed that the baseline CD4 +T cell count was <200/μl, subtype B, subtype B+C, CRF01-AE subtype, CRF55-01B subtype and 01-BC subtype was the influential factor of drug resistance before treatment (the chi-square values are respectively 4.577, 8.202, 4.416, 5.206, 7.603 and 4.804, P<0.05). Conclusion:The newly reported HIV/AIDS population in Anhui Province from 2020 to 2023 has a variety of viral gene subtypes, and NNRTIs are the main types of drug resistance gene mutations before treatment. Attention should be paid to the number of baseline CD4 +T cells, the duration of antiviral treatment, and the distribution of gene subtypes to reduce the drug resistance of HIV/AIDS patients before treatment.

Background::We previously reported that activation of the cell cycle in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) enhances their remuscularization capacity after human cardiac muscle patch transplantation in infarcted mouse hearts. Herein, we sought to identify the effect of magnesium lithospermate B (MLB) on hiPSC-CMs during myocardial repair using a myocardial infarction (MI) mouse model.Methods::In C57BL/6 mice, MI was surgically induced by ligating the left anterior descending coronary artery. The mice were randomly divided into five groups ( n = 10 per group); a MI group (treated with phosphate-buffered saline only), a hiPSC-CMs group, a MLB group, a hiPSC-CMs + MLB group, and a Sham operation group. Cardiac function and MLB therapeutic efficacy were evaluated by echocardiography and histochemical staining 4 weeks after surgery. To identify the associated mechanism, nuclear factor (NF)-κB p65 and intercellular cell adhesion molecule-1 (ICAM1) signals, cell adhesion ability, generation of reactive oxygen species, and rates of apoptosis were detected in human umbilical vein endothelial cells (HUVECs) and hiPSC-CMs. Results::After 4 weeks of transplantation, the number of cells that engrafted in the hiPSC-CMs + MLB group was about five times higher than those in the hiPSC-CMs group. Additionally, MLB treatment significantly reduced tohoku hospital pediatrics-1 (THP-1) cell adhesion, ICAM1 expression, NF-κB nuclear translocation, reactive oxygen species production, NF-κB p65 phosphorylation, and cell apoptosis in HUVECs cultured under hypoxia. Similarly, treatment with MLB significantly inhibited the apoptosis of hiPSC-CMs via enhancing signal transducer and activator of transcription 3 (STAT3) phosphorylation and B-cell lymphoma-2 (BCL2) expression, promoting STAT3 nuclear translocation, and downregulating BCL2-Associated X, dual specificity phosphatase 2 (DUSP2), and cleaved-caspase-3 expression under hypoxia. Furthermore, MLB significantly suppressed the production of malondialdehyde and lactate dehydrogenase and the reduction in glutathione content induced by hypoxia in both HUVECs and hiPSC-CMs in vitro. Conclusions::MLB significantly enhanced the potential of hiPSC-CMs in repairing injured myocardium by improving endothelial cell function via the NF-κB/ICAM1 pathway and inhibiting hiPSC-CMs apoptosis via the DUSP2/STAT3 pathway.