Cholesterol,as an important component of cell membranes,plays a multifaceted role in mediating tumor immunomodulation and drug intervention.In case of cholesterol metabolic imbalance,the accumulation of cholesterol metabolic intermediates,the changes in concentrations,and the regulation of related signaling pathways can affect tumor immunity by promoting inflammation and inhibiting immune cell function.Preclinical and clinical studies have shown that controlling cholesterol metabolism can inhibit tumor growth,re-shape body immune regulation,and enhance antitumor immunity.A deep understanding of the association between immune cells and cholesterol metabolic pathways in the tumor microenvironment can help to develop novel drugs targeting cholesterol metabolism.This article reviews the multifaceted role of cholesterol and its derived metabolites in the tumor microenvironment by regulating various types of immune cells such as myeloid-derived suppressor cells,tumor-associated macrophages,dendritic cells,and T-lymphocytes,as well as the characteristics of tumor immunomodulation mediated by cholesterol metabolism and the advances in pharmaceutical re-search on improving the immune function of the body by intervening against cholesterol,in order to further provide new ideas and a thera-peutic basis for cholesterol modulation and intervention in tumor im-munotherapy.

Objective:To describe demographic,clinical and physiological characteristics,treatment between first-episode major depressive disorder(MDD)and relapse MDD,and to explore characteristics of relapse MDD.Methods:Totally 858 patients who met the diagnostic criteria for depression of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5),were included by using the Mini International Neuropsychiatric Interview(MINI),Clinician-Rated Dimensions of Psychosis Symptom Severity,and Hamilton Depression Scale etc.Among them,529(58.6％)were first-episode depression and 329(36.0％)were relapsed.The differences of demographic characteristics,clinical and physiological characteristics,treatment were compared byx2test and Kruskal-Wallis rank sum test.Multivariate logistic regression was used to explore the characteristics of MDD recur-rence.Results:Compared to first-episode MDD,relapse MDD had more comorbidity(OR=2.11,95％CI:1.00-4.44),more days out of role(OR=1.26,95％CI:1.01-1.56),more history of using psychiatric drug more than one month(OR=1.41,95％CI:1.02-1.97)and electroconvulsive therapy(OR=3.23,95％CI:1.42-7.36),and higher waist-hip ratio(OR=33.88,95％CI:2.88-399.32).Conclusion:Relapse MDD has positive as-sociation with comorbidity of mental disorders,out of role,and higher waist-hip ratio.

Objective:To investigate the safety, feasibility and accuracy of esophageal sponge cytology in esophageal carcinoma screening in high-incidence districts.Methods:Opportunistic screening for esophageal carcinoma was conducted on individuals aged 40-75 years with high-risk factors for esophageal carcinoma and visited out-patient clinic in Lianshui People's Hospital from May 2021 to June 2022. A new esophageal cell collector independently developed in China was used for esophageal sponge cytology sampling followed by cytopathological analysis. Atypical squamous cells or more severe lesions were defined as positive esophageal sponge cytology. Then gastroscopy was performed, and all suspicious areas under the endoscopy were biopsied for histopathological examination. Gastroscopy, biopsy histopathology and esophageal sponge cytology were conducted blindly in pairs. Outcome measures included adverse reactions during sampling, subject tolerability (using a visual simulation score), sampling quality, and diagnostic efficacy of esophageal sponge cytology using gastroscopy plus biopsy histopathology as the gold standard.Results:A total of 1 590 patients completed the screening program. During esophageal sponge cytology sampling, no serious adverse events were observed, and the adverse reactions were mainly manifested as vomiting during sampling [0.31% (5/1 590)] and sore throat after sampling [2.45% (39/1 590)], all of which resolved spontaneously without further medical intervention. The majority of subjects [98.62% (1 568/1 590)] reported good tolerance during the procedure. After sampling, 1 526 (95.97%) subjects had completely expanded sponge material, meeting the standard of good sampling quality. The scanning analysis of the digital pathology system showed that the number of sampled cells in 1 590 subjects ranged (2.01-4.00)×10 6, with a median of 3.48×10 6 cells, which could meet the requirements for interpreting cytological results. Using the positive esophageal sponge cytology for the diagnosis of esophageal carcinoma including high-grade intraepithelial neoplasia, esophageal squamous cell carcinoma and adenocarcinoma of esophagogastric junction, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 98.57% (69/70), 91.51% (1 391/1 520), 34.85% (69/198), 99.93% (1 391/1 392), and 91.82% (1 460/1 590), respectively. Conclusion:Esophageal sponge cytology presents promising diagnostic efficacy for esophageal carcinoma screening, offering a simple, safe, convenient, and effective approach in high-incidence esophageal carcinoma regions.

Objective:To explore the feasibility and effect of remote medical education model using online film reading training to improve the ability of ophthalmologists in the Xinjiang Uygur Autonomous Region (hereinafter referred to as "Xinjiang Region" ) in diagnosing fundus diseases.Methods:The three-level film reading training system of Xinjiang Production and Construction Corps system division hospital-Corps Hospital-Peking Union Medical College Hospital was established. From June 2022 to January 2023, 4 159 posterior color fundus images were continuously collected from Department of Ophthalmology of Xinjiang Corps Hospital and 4 divisional hospitals in the Corps medical system. Among them, hypertensive retinopathy, diabetic retinopathy, exudative age-related macular degeneration (AMD), atrophic AMD and retinal vein occlusion were 3 073, 651, 43, 186 and 206 cases, respectively. The images were divided into 3 rounds (first, second and last) according to the proportion of diseases. The doctors who participated in the training (hereinafter referred to as the "training") were 15 ophthalmologists from the Corps Hospital of Xinjiang Region and the division hospital of the Corps system. There were 7 male and 8 female. Age was (38.1±4.0) years. The titles of senior, deputy senior, intermediate and junior are 1, 6, 5 and 3 respectively; Bachelor's degree and master's degree are 13 and 2 respectively. The working time of fundus disease specialty was (9.6±3.3) years. The film reading system training was conducted before the first round of labeling, and after each round of film reading, the doctors of Peking Union Medical College Hospital gave feedback and explanation on the film reading results. The diagnostic consistency, sensitivity and specificity were compared by paired sample t test. Spearman or Pearson correlation analysis was conducted between the improvement of diagnostic level and professional title, education, age and working hours of ocular fundus disease. Results:All the participating doctors completed the first, second and last reading. After each round of film reading, the film reading summary was carried out for 2 hours. The average diagnostic agreement rates of participating physicians were 53.0%, 67.0% and 75.0%, respectively. The sensitivity and specificity were 0.38, 0.69, 054 and 0.66, 0.85, 0.96, respectively. There was significant difference between the first and last examination ( P<0.001). The sensitivity of the second reading was significantly higher than that of the first reading, and the sensitivity of the last reading was significantly lower than that of the second reading, with statistical significance ( P<0.05). The specificity of the second reading was significantly higher than that of the first reading, and the last reading was significantly higher than that of the second reading, with statistical significance ( P<0.05). There was no significant correlation ( P>0.05) between the improvement of diagnostic level of participating physicians and educational background ( Rho=0.07), professional title ( Rho=0.13), age ( r=0.20), and working time of ophthalmofundus disease specialty ( r=0.26). Conclusions:Relying on the three-level online telemedicine training, it can improve the ability of ophthalmologists in Xinjiang region to diagnose fundus diseases. The preliminary telemedicine education model has demonstrated potential for feasibility and effectiveness in remote areas with inadequate medical resources.

Objective:To explore the feasibility and effect of remote medical education model using online film reading training to improve the ability of ophthalmologists in the Xinjiang Uygur Autonomous Region (hereinafter referred to as "Xinjiang Region" ) in diagnosing fundus diseases.Methods:The three-level film reading training system of Xinjiang Production and Construction Corps system division hospital-Corps Hospital-Peking Union Medical College Hospital was established. From June 2022 to January 2023, 4 159 posterior color fundus images were continuously collected from Department of Ophthalmology of Xinjiang Corps Hospital and 4 divisional hospitals in the Corps medical system. Among them, hypertensive retinopathy, diabetic retinopathy, exudative age-related macular degeneration (AMD), atrophic AMD and retinal vein occlusion were 3 073, 651, 43, 186 and 206 cases, respectively. The images were divided into 3 rounds (first, second and last) according to the proportion of diseases. The doctors who participated in the training (hereinafter referred to as the "training") were 15 ophthalmologists from the Corps Hospital of Xinjiang Region and the division hospital of the Corps system. There were 7 male and 8 female. Age was (38.1±4.0) years. The titles of senior, deputy senior, intermediate and junior are 1, 6, 5 and 3 respectively; Bachelor's degree and master's degree are 13 and 2 respectively. The working time of fundus disease specialty was (9.6±3.3) years. The film reading system training was conducted before the first round of labeling, and after each round of film reading, the doctors of Peking Union Medical College Hospital gave feedback and explanation on the film reading results. The diagnostic consistency, sensitivity and specificity were compared by paired sample t test. Spearman or Pearson correlation analysis was conducted between the improvement of diagnostic level and professional title, education, age and working hours of ocular fundus disease. Results:All the participating doctors completed the first, second and last reading. After each round of film reading, the film reading summary was carried out for 2 hours. The average diagnostic agreement rates of participating physicians were 53.0%, 67.0% and 75.0%, respectively. The sensitivity and specificity were 0.38, 0.69, 054 and 0.66, 0.85, 0.96, respectively. There was significant difference between the first and last examination ( P<0.001). The sensitivity of the second reading was significantly higher than that of the first reading, and the sensitivity of the last reading was significantly lower than that of the second reading, with statistical significance ( P<0.05). The specificity of the second reading was significantly higher than that of the first reading, and the last reading was significantly higher than that of the second reading, with statistical significance ( P<0.05). There was no significant correlation ( P>0.05) between the improvement of diagnostic level of participating physicians and educational background ( Rho=0.07), professional title ( Rho=0.13), age ( r=0.20), and working time of ophthalmofundus disease specialty ( r=0.26). Conclusions:Relying on the three-level online telemedicine training, it can improve the ability of ophthalmologists in Xinjiang region to diagnose fundus diseases. The preliminary telemedicine education model has demonstrated potential for feasibility and effectiveness in remote areas with inadequate medical resources.

Objective:To explore the clinical risk factors of post-transplantation diabetes mellitus (PTDM) and establish a risk prediction model in kidney recipients.Methods:The clinical data and postoperative bedside measurements of blood glucose (BG) were retrospectively reviewed for 305 renal transplant recipients at First Affiliated Hospital of Zhejiang University School of Medicine from October 2018 to August 2019.According to whether or not PTDM occurred, they were assigned into two groups of PTDM (n=34) and non-PTDM (n=271). Risk factors were screened through single/multi-factor Logistic regression and PTDM prediction model was established.Results:The incidence rate of PTDM was 11.15%(34/305). Logistic regression analysis indicated that deceased donor, age ≥40 years, female, pre-hemoglobin A1c (Pre-HbA1c) and postoperative bedside BG value ≥11.1 mmol/L were the correlated factors for the occurrence of PTDM.Among them, female ( OR=3.13, 95% CI: 1.28-7.61), Pre-HbA1c ( OR=2.05, 95% CI: 1.12-3.74) and BG ≥11.1 mmol/L at 4pm Day 2/3 post-operation ( OR=19.08, 95% CI: 4.34-83.87) were risk factors for the occurrence of PTDM, The area under the model curve was 0.86 (95% CI: 0.79-0.93) with a Jordan index of 0.65, a sensitivity of 82.8% and a specificity of 82.3%. Conclusions:Female, Pre-HbA1c and fasting BG at 4 pm Day 2/3 post-operation ≥ 11.1 mmol/L are risk factors for the occurrence of PTDM.The prediction model has a decent predictive value.It is conducive to early clinical interventions and lowering the incidence rate of PTDM.

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

Objective To detect the change of exoression level of plasma microRNA‐21(miR‐21) and TGF‐β1 in cardiac remode‐lin affer acute myocardial infarction(AMI) of the pateins .Methods 200 pateints with AMI and 100 normal controls(age ,sex matched) were enrolled .Blood samples were obtained from the normal controls and patients with AMI on the 3 days ,7 days and 14 days .Real‐time PCR was developed to detect the expression of miR‐21 and TGF‐β1 in plasma .Results The expression of miR‐21 was significantly up‐regulation in the 3 days ,7 days and 14 days in MI group than that cntrol group ,0 .74 ± 0 .21 vs .2 .62 ± 0 .23 , vs .3 .67 ± 0 .25 ,vs .4 .13 ± 0 .27 up‐regulation in the 3 days ,7 days and 14 days in MI group than that cntrol group ,0 .98 ± 0 .18 vs .2 .35 ± 0 .24 ,vs .3 .67 ± 0 .25 ,vs .4 .13 ± 0 .27 ,P<0 .05 ,respectively .The expression of miR‐21 and TGF‐β1 were up‐regulation with the change of cardiac function .Positive relationship between miRNA‐21 expression and LVDd (r=0 .757 ,P<0 .05);Positive relationship between TGF‐β1 mRNA expression and LVDd(r=0 .701 ,P<0 .05) .Conclusion The expression of miR‐21 and TGF‐β1 were up‐regulation in cardiac remodelin affer AMI of the pateins ,which involved in regulation in cardiac remodelin affer AMI .

BACKGROUND:Because macrophages play an important role in the body’s inflammatory response, the detection of the impact of biological materials on the behavior of macrophages can assess the immunogenicity of materials. OBJECTIVE: To analyze the activation effect of decelularized extracelular matrix materials on macrophages. METHODS: The peritoneal macrophages of BALB/c mouse were obtained and cultured by dividing into five groups. Control group was simple cel culture group, experimental group 1 was acelular matrix membrane material directly contacting with macrophage for culture, experimental group 2 was fresh pericardial material directly contacting with the macrophage for culture, experimental group 3 was acelular matrix membrane material indirectly contacting with macrophages for culture, experimental group 4 was fresh pericardium material indirectly contacting with macrophages for culture. After 24 hours of culture, the secretion of nitric oxide and cytokines in cel culture supernatant was determined. After 48 hours of culture, the absorbance value was determined by MTT method and the toxicity grading was determined. RESULTS AND CONCLUSION: The toxicity grading in experimental groups 1-4 was respectively grades 2, 4, 0, 2. The nitric oxide level in experimental groups 1 and 2 was higher than that in the control group (P < 0.05), and the nitric oxide level in the experimental group 2 was higher than that in the experimental group 1 (P < 0.05). There were no significant differences in interleukin-2, interleukin-4,interferon γ, interleukin-17A and interleukin-10 levels between these five groups. The interleukin-6 level in the experimental group 2 was higher than that in the control group (P < 0.05); The expression levels of tumor necrosis factors in experimental group 1, 2 and 4 were higher than those in the control group (P < 0.05), and experimental group 2 higher than the experimental group 1 (P < 0.05), experimental group 1 higher than the experimental group 4 (P < 0.05). These results show that acelular matrix material can activate macrophages in direct contact.

Objective To explore the value of 64-row helical CT multi-phase enhancement scan combined with angiography (CTA)in the diagnosis of pulmonary mass.Methods Two hundred and sixty-five patients with pulmonary mass confirmed by pa-thology were checked,analyzed the CT sign of multi-phase enhancement scan and the blood supply of pulmonary mass displayed by CTA.Results Lung cancer was mainly supplied by bronchial arteries,some by body arteries,the feeding arteries display rate of lung cancer group was significantly higher than that of benign disease group(P <0.05).CT enhancement peak value of lung cancer group was significantly higher than that of tuberculoma group,inflammatory pseudotumor group and hamartoma group(P <0.05), but no significant difference between hemanginoma group(P >0.05).Enhancement dynamic curves of lung cancer group was differ-ent from benign lesion groups:Lung cancer without obvious enhancement in pulmonary artery phase,CT value increased rapidly in aorta phase,120 s reached peak,and declined slowly in delay phase;CT value of tuberculoma was increased slowly without obvious peak;CT value of inflammatory increased gradually in pulmonary artery phase,90 s reached the peak;hamartoma was no obvious enhancement;Hemangioma enhanced rapidly after strengthening in the pulmonary artery phase,reached the peak at about 15 s,and then decreased slowly.Conclusion 64-row helical CT multi-phase enhancement scan combined with angiography have important clinical value,which can differentiate malignant mass from benign ones.