ObjectiveTo investigate the trend and influencing factors of newly reported human immunodeficiency virus (HIV) positivity rate among men who had sex with men (MSM) in Shanghai from 2021 to 2024, and to provide evidence for formulating scientific prevention and control measures of AIDS. MethodsMultiple rounds of cross-sectional questionnaire surveys were conducted among MSM by Shanghai Qing’ai Health Promotion Center. Pearson and Cochran-Armitage trend χ² tests were used to analyze the differences and changes in population characteristics and newly reported HIV positivity rates. A logistic regression model was applied for multivariate analyses of factors associated with newly reported HIV positivity. ResultsA total of 1 653 MSM who had not been previously diagnosed with HIV infection were surveyed. The newly reported HIV positivity rates in 2021, 2023, and 2024 were 7.87%, 3.91%, and 3.06%, respectively, showing a decreasing trend (χ²_trend=13.460, P_trend<0.001). Multivariate analyses revealed that MSM aged 18‒<25 years, residing locally for <1 year, identifying as bisexual, lacking HIV knowledge, and having ≥10 same-sex partners in the past 6 months exhibited higher newly reported HIV positivity rates. Conversely, MSM knowledgeable about HIV prevention, residing locally for 1‒5 years, and engaging in oral sex with male partners in the past 6 months demonstrated lower HIV positivity rates. Annual analyses revealed that MSM with HIV knowledge had lower newly reported HIV positivity rates in 2023 and 2024 (aOR=0.300, 95%CI: 0.811‒0.111; aOR=0.202, 95%CI: 0.085‒0.483). ConclusionThe newly reported HIV positivity rate among MSM in Shanghai from 2021 to 2024 showed a decline. Future interventions should focus on young and mobile MSM, strengthen HIV knowledge education through platforms such as the internet, promote safe sexual behaviors and regular testing, and further expand the coverage of pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) to control HIV transmission within this population.

Ionizing radiation (IR) is a genotoxic agent that can play an important role in the occurrence and development of various diseases by inducing epigenetic changes. Studies have shown that the basic mechanisms of IR-induced epigenetic changes include abnormal DNA methylation, increased oxidative stress levels, changes in histone modifications, and regulation by microRNAs. These can lead to health hazards such as malignant tumors, genetic effects, nervous system damage, circulatory system diseases, and radiation-induced cataracts. This article collected relevant literatures regarding epigenetic changes induced by IR from 2005 to 2024, and reviewed the basic mechanisms of IR-induced epigenetic changes and the associated disease risks, providing the reference for radiation protection in occupational exposure and radiotherapy.

Background::Pancreatic ductal adenocarcinoma (PDAC) is one of the main types of malignant tumor of the digestive system, and patient prognosis is affected by difficulties in early diagnosis, poor treatment response, and a high postoperative recurrence rate. Carbohydrate antigen 19-9 (CA19-9) has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients. Nevertheless, the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated.Methods::We performed single-cell RNA sequencing on six samples pathologically diagnosed as PDAC (three CA19-9-positive and three CA19-9-negative PDAC samples) and two paracarcinoma samples. We also downloaded and integrated PDAC samples (each from three CA19-9-positive and CA19-9-negative patients) from an online database. The dynamics of the proportion and potential function of each cell type were verified through immunofluorescence. Moreover, we built an in vitro coculture cellular model to confirm the potential function of CA19-9. Results::Three subtypes of cancer cells with a high ability to produce CA19-9 were identified by the markers TOP2A, AQP5, and MUC5AC. CA19-9 production bypass was discovered on antigen-presenting cancer-associated fibroblasts (apCAFs). Importantly, the proportion of immature ficolin-1 positive (FCN1+) macrophages was high in the CA19-9-negative group, and the proportion of mature M2-like macrophages was high in the CA19-9-positive group. High proportions of these two macrophage subtypes were associated with an unfavourable clinical prognosis. Further experiments indicated that CA19-9 could facilitate the transformation of M0 macrophages into M2 macrophages in the tumor microenvironment. Conclusions::Our study described CA19-9 production at single-cell resolution and the dynamics of the immune atlas in CA19-9-positive and CA19-9-negative PDAC. CA19-9 could promote M2 polarization of macrophage in the pancreatic tumor microenvironment.

Objective:An ICP-MS method was established for the determination of arsenic(As),cadmium(Cd),mercury(Hg),lead(Pb),cobalt(Co),nickel(Ni),vanadium(V),lithium(Li),antimony(Sb),copper(Cu)and other 10 elements in pharmaceutical excipients sucrose to assess their risks.Methods:The pharmaceuti-cal excipient sucrose was dissolved in 0.1％HN03 solution directly,and the contents of 75 As,111Cd,202Hg,208Pb,59 Co,60 Ni,51V,7 Li,121 Sb,and 63 Cu in sucrose were determined by the ICP-MS method with the optimized instru-mental parameters in the STD mode.Results:The results showed that the linearity of the method was great in the range of 0-100 ng·mL-1 for As,Cd,Pd,Co,Ni,V,Li,Sb and Cu(the correlation coefficient r was not less than 0.99),and the linearity of the method was good in the range of 0-2 ng·mL-1 for Hg(r=0.999 1).The average recoveries for the 10 elements were in the range of 99.8％-100.0％,and the RSDs were less than 5％(n=6).Conclusion:The method is easy to operate and has high accuracy.It can be used for the determination of 10 elemental impurities in pharmaceutical excipient sucrose.It can be seen that the content of the above ten elements in sucrose is much lower than the specified value in ICH Q3D,and the risk is small.The heavy metal item can no longer be considered separately when revising the standard.

The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.

Objective:To explore and analyze the clinical features and prognostic factors of secondary intestinal diffuse large B-cell lymphoma(SI-DLBCL),in order to provide reference for the basic research and clinical diagnosis and treatment of secondary lymphoma of rare sites in the field of hematology.Methods:The clinical data of 138 patients with SI-DLBCL admitted to Fujian Medical University Union Hospital from June 2011 to June 2022 were collected and sorted,the clinical and pathological features,diagnosis,treatment and prognosis were analyzed.Cox regression risk model was used to conduct univariate and multivariate analysis on the prognostic risk factors.Results:Among the 138 patients with SI-DLBCL included in this study,85(61.59％)were male,53(38.41％)were female,the median age of onset was 59.5(16-84)years,the clinical manifestations lacked specificity,the first-line treatment regimen was mainly chemotherapy(67.39％),94 cases(68.12％)received chemotherapy alone,40 cases(28.98％)were treated with chemotherapy combined with surgery,and 4 cases(2.90％)were treated with surgery alone.The median follow-up time was 72(1-148)months.Among the 138 patients with SI-DLBCL,79(57.25％)survived,34(24.64％)died,25 cases(18.12％)lost to follow-up,the PFS rates of 1-year,3-year and 5-year were 57.97％,49.28％and 32.61％,and the OS rates of 1-year,3-year and 5-year were 60.14％,54.35％and 34.06％,respectively.The results of univariate Cox regression analysis showed that age,Lugano stage and IPI score were the influencing factors of OS in SI-DLBCL patients,and age,Lugano stage and IPI score were the influencing factors of PFS in SI-DLBCL patients.The results of multivariate Cox analysis showed that Lugano stage was an independent prognostic factor affecting OS and PFS in SI-DLBCL patients.Conclusion:Patients with SI-DLBCL are more common in middle-aged and elderly men,and the early clinical manifestations lack specificity,and the first-line treatment regimen is mainly R-CHOP chemotherapy,and Lugano stage is an independent prognostic factor affecting OS and PFS in SI-DLBCL patients.

Objective:To evaluate the values of 18F-PI-2620 PET/CT brain imaging with SUV ratio (SUVR) in the assessment of tau protein deposition in the brain of patients with different cognitive disorders and its correlation with cognition. Methods:This was a cross-sectional study. From December 2019 to November 2022, a total of 67 subjects including 54 patients with Alzheimer′s disease (AD; 21 males, 33 females, age (68.6±7.8) years), 7 patients with mild cognitive impairment (MCI; 1 male, 6 females, age (63.1±11.2) years) and 6 healthy controls (HC; 4 males, 2 females, age (69.0±5.8) years) were enrolled retrospectively in Renji Hospital. All participants were examined by 18F-PI-2620 PET/CT. SUVRs of brain regions were obtained, including frontal lobe, temporal lobe, occipital lobe, parietal lobe, insular lobe, whole brain, as well as 10 independent brain ROIs (amygdala, orbitofrontal cortex, cingulate gyrus, superior occipital gyrus, superior parietal gyrus, inferior angular gyrus, precuneus, inferior temporal gyrus, entorhinal cortex and parahippocampal gyrus), with inferior cerebellum cortex as the reference region. All participants were estimated by cognitive scales(mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA)). One-way analysis of variance and the least significant difference t test were used to compare the differences of SUVR in each brain region among HC, MCI and AD groups. ROC curve analysis was used to determine the optimal cut-off values of SUVR in each brain region for the differential diagnosis of AD-MCI and AD-HC. Pearson correlation analysis was employed to examine the correlations of SUVR with cognitive scale scores. Results:The SUVR of whole brain was 1.40±0.31 in AD group, 1.08±0.19 in MCI group, and 1.01±0.12 in HC group. SUVR analysis in the whole brain and each brain region could distinguish AD from HC, AD from MCI ( F values: 1.76-10.09, t values: 2.98-7.47, all P<0.05), but could not distinguish HC from MCI ( t values: 0.17-1.53, all P>0.05). ROC curve analysis showed that the best cut-off value of SUVR was 1.18 for whole brain (AUC=0.89), 1.13 for amygdala (AUC=0.94) and 1.26 for parahippocampal gyrus (AUC=0.94) for differential diagnosis of AD and HC, which was 1.06 for whole brain (AUC=0.82), 1.18 for amygdala (AUC=0.88) and 1.28 (AUC=0.88) for infratemporal gyrus to differential diagnosis of AD and MCI. SUVRs of the whole brain, frontal, occipital, parietal, temporal and insula were significantly negatively correlated with MMSE and MoCA cognitive scale scores ( r values: from -0.64 to -0.40, all P<0.05). Conclusions:SUVR quantitative analysis in 18F-PI-2620 PET imaging can assist the differential diagnosis of AD and HC, AD and MCI. The SUVRs of whole brain and five lobes show negative correlations with MMSE and MoCA scores.

Objective:To assess the diagnostic efficiency of 18F-FDG PET for Alzheimer′s disease (AD) in patients with memory impairment. Methods:A retrospective analysis was conducted on 96 patients (40 males, 56 females, age: 69.0(62.8, 74.0) years) initially diagnosed with memory impairment in Renji Hospital, School of Medicine, Shanghai Jiao Tong University between August 2019 and September 2023. The amyloid-tau-neurodegeneration (ATN) criteria, based on 18F-AV45+ 18F-PI-2620 PET/CT+ MRI imaging results, were used as the diagnostic standard for AD. Visual analysis (temporoparietal or posterior cingulate cortex (PCC) hypometabolism) and semi-quantitative analysis methods (PET-SCORE and NeuroQ software analysis (SUV ratio, SUVR)) were applied to evaluate the diagnostic efficiency of 18F-FDG PET imaging for AD. Diagnostic efficiencies of visual assessment and semi-quantitative parameters were compared by χ2 test. Additionally, Pearson correlation analysis was performed to examine the relationship between results of PET-SCORE and cognitive scales. Results:Of the 96 patients initially diagnosed with memory impairment, 61 were clinically diagnosed with AD, while 35 were non-AD patients. Visual assessment of temporoparietal hypometabolism showed the highest sensitivity (91.80%, 56/61), which was significantly different from the sensitivities of PET-SCORE (40.98%(25/61); χ2=29.03, P<0.001) and visual assessment of PCC hypometabolism (77.05%(47/61); χ2=5.82, P=0.016). While semi-quantitative assessment using PET-SCORE demonstrated the highest specificity (100%, 35/35), which was significantly different from the specificities of visual assessment methods (temporoparietal hypometabolism: 17.14%(6/35), χ2=27.03, P<0.001; PCC hypometabolism: 54.29%(19/35), χ2=14.06, P<0.001). PET-SCORE exhibited statistically significant correlations with Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Activities of Daily Living (ADL) scores ( r values: -0.38, -0.36, 0.31, all P<0.01). Conclusions:Among patients initially diagnosed with memory impairment, visual assessment in 18F-FDG PET imaging analysis demonstrates higher sensitivity, while semi-quantitative analysis using PET-SCORE exhibits higher specificity. PET-SCORE shows statistically significant correlation with the severity of cognitive decline.

Objective:To explore the short-term clinical efficacy, safety and patients' prognostic influencing factors of CyberKnife for the treatment of brain metastases in non-small cell lung cancer (NSCLC).Methods:A retrospective case series study was conducted. The clinical data of 58 NSCLC patients who received CyberKnife treatment for brain metastases at Jilin Cancer Hospital from July 2020 to January 2022 were retrospectively analyzed. At 3 months after CyberKnife treatment for brain metastases, and the efficacy of radiotherapy was evaluated on the basis of changes of brain metastases detected by contrast-enhanced magnetic resonance imaging (MRI) of the head. Overall survival (OS) and local recurrence-free survival (LRRFS) were analyzed in 58 patients by using the Kaplan-Meier method; the efficacy of cumulative brain metastasis volume for determining the survival of CyberKnife-treated NSCLC patients with brain metastases was analyzed by using the receiver operating characteristic (ROC) curve with the survival status of patients during the follow-up period as the gold standard, and the optimal cut-off value of cumulative brain metastasis volume was obtained; the clinical factors affecting OS and LRRFS of CyberKnife-treated NSCLC patients with brain metastases were analyzed by univariate and multivariate Cox proportional hazards models, and the adverse reactions associated with CyberKnife treatment were evaluated.Results:Among the 58 patients, 26 (44.8%) were male and 32 (55.2%) were female, with a median age [ M ( Q1, Q3)] of 64 years old (56 years old, 70 years old); there were 1-7 brain metastatic lesions in each patient, and there were 98 brain metastatic lesions in the 58 patients. There were 2 deaths (3.4%) within 3 months after CyberKnife treatment. At 3 months after treatment, there were 3 cases (5.4%) in complete remission, 36 cases (64.3%) in partial remission, 13 cases (23.2%) in stable disease, and 4 cases (7.1%) in disease progression in the remaining 56 patients. ROC curve analysis showed that the area under the curve for determining the survival of CyberKnife-treated NSCLC patients with brain metastases based on the cumulative brain metastasis volume was 0.593 (95% CI: 0.423-0.763), and the optimal cut-off value of cumulative brain metastasis volume was 15 cm 3. Median follow-up time was 12.6 months (7.5 months, 17.9 months). The 6- and 12-month OS rates were 91.3% and 79.5%, respectively, and the 6- and 12-month LRRFS rates were 93.0% and 89.2%, respectively. Multivariate Cox regression analysis showed that the Karnofsky functional status score (>70 points vs. ≤70 points, HR= 0.103, 95% CI: 0.019-0.545, P = 0.007), control of extracranial tumor (controlled vs. uncontrolled, HR = 0.145, 95% CI: 0.049-0.429, P < 0.001), cumulative brain metastasis volume (≤15 cm 3vs. >15 cm 3, HR = 0.105, 95% CI: 0.028-0.399, P = 0.001) were independent influencing factors for poor OS, and the control of extracranial tumor (controlled vs. uncontrolled, HR = 0.062, 95% CI: 0.006-0.616, P = 0.018), cumulative brain metastasis volume (≤15 cm 3vs. >15 cm 3, HR = 0.440, 95% CI: 0.007-0.292, P = 0.001), and target area total bioequivalent dose (BED) (≤60 Gy vs. >60 Gy, HR = 5.299, 95% CI: 1.020-27.530, P = 0.047) were independent influencing factors for poor LRRFS. Only grade 1-2 headache [53.5% (31/58)], nausea and vomiting [36.2% (21/58)] and other adverse reactions occurred after treatment, and no ≥grade 3 adverse reactions occurred. Conclusions:CyberKnife treatment for NSCLC brain metastases has high local control rate and short-term survival rate with mild adverse effects. Karnofsky functional status score, control of extracranial tumor and cumulative brain metastasis volume may affect OS of CyberKnife-treated NSCLC patients with brain metastases, and the control of extracranial tumor, cumulative brain metastasis volume and total BED may affect local recurrence.

Objective To investigate the relationship between the expression of Klotho,apoptosis-related factors and oxidative stress injury of the trabecular meshwork in patients with glaucoma.Methods Totally 86 patients(86 eyes)with glaucoma admitted to our hospital from October 2021 to October 2023 were selected as the study group.Tissue sam-ples of trabecular meshwork were obtained during the operation.Trabecular meshwork donor tissues(45 cases)from pa-tients with non-eye diseases were taken as the control group.Hematoxylin-Eosin(HE)staining was used to examine the histopathological characteristics,and the expression levels of Klotho,apoptosis-associated speck-like protein containing a CARD(ASC),cysteine-aspartic proteases-1(Caspase-1),superoxide dismutase(SOD)and peroxidase(POD)in trabecu-lar meshwork tissues were detected.The expression levels of Klotho,ASC,Caspase-1,SOD and POD of patients in the two groups and those expression levels in glaucoma patients with different average visual field defects were compared.The cor-relation between expression levels of Klotho,apoptosis-related proteins and oxidative stress injury of the trabecular mesh-work in glaucoma patients was analyzed by the Pearson method.Results HE staining results showed that the trabecular meshwork structure of patients in the study group was disorganized,with interlaced layers,thickened trabecular bundles and cell nucleus shrinkage,while the lamellas of trabecular meshwork tissues and trabecular cell bundles in the control group were orderly arranged,with normal forms of trabecular cells.In the study group,the expression level of Klotho in trabecular meshwork tissues was lower and the expression levels of ASC and Caspase-1 were higher than those of the con-trol group(all P＜0.05).There were statistically significant differences in the expression levels of Klotho,ASC,Caspase-1,SOD and POD in patients with different average visual field defects(all P＜0.05).With the increase in disease severity,the expressions of Klotho and SOD showed a significant decrease,while the expressions of ASC,Caspase-1 and POD showed a significant increase(all P＜0.05).Pearson correlation analysis showed that Klotho in the trabecular mesh work was negatively correlated with POD and positively correlated with SOD,while ASC and Caspase-1 were positively correlated with POD and negatively correlated with SOD(all P＜0.05).Conclusion The expression of Klotho is low in the trabec-ular meshwork tissues of patients with glaucoma,while the expressions of ASC and Caspase-1 are high.These expressions are correlated with the average visual field defect,reflecting the stress injury degree of trabecular meshwork tissues.