Kinetochore scaffold 1 downregulation suppressed the development of non-small cell lung cancer by inactivating the phosphatidylinositol 3 kinase/protein kinase B (AKT)/nuclear factor-kappa B pathway.

Kinetochore scaffold 1 (KNL1) is indispensable for generating motile micro-tubule attachments and isolating chromosomes. KNL1 is highly expressed in multiple middle-route tissues and promotes tumor development. However, how it functions in non-small cell lung cancer (NSCLC) is unclear. Real-time quantitative PCR (RT-qPCR) and Western blotting (WB) were used to determine KNL1 expression in NSCLC tissues and cells. The sh-KNL1 or oe-KNL1 was transfected into NSCLC cells. The colony formation assay, cell counting kit-8 (CCK-8) assay, and flow cytometry were used to evaluate cell proliferation and apoptosis. A transwell assay was used to monitor invasion and migration. The CCK-8 assay was used to measure NSCLC cell sensitivity to chemotherapy drugs. WB confirmed the protein levels of apoptosis-related proteins, cell cycle-associated proteins, and the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT)/nuclear factor kappaB (NF-κB) pathway. A PI3K/AKT/NF-κB pathway inhibitor was used to intervene in NSCLC cell transfection along with oe-KNL1, thus revealing the function of the pathway in carcinogenicity mediated by KNL1. In result KNL1 expression was substantially increased in NSCLC tissues and cells. High-level KNL1 expression is related to the poor prognosis of NSCLC patients. KNL1 silencing bolstered promoted NSCLC cell apoptosis and inhibited proliferation, cell cycle progression, invasion, and EMT, whereas KNL1 silencing had the opposite effect. KNL1 knockdown increased NSCLC cell sensitivity to chemical drugs. KNL1 promoted PI3K/AKT/NF-κB pathway activation, while PI3K/AKT/NF-κB pathway inhibition weakened the procancer effect mediated by KNL1 overexpression but had little influence on KNL1 levels. We conclude that KNL1 activates the PI3K/AKT/NF-κB pathway to increase NSCLC progression and attenuate NSCLC sensitivity to chemotherapy drugs.

Isolated non-immune mediated second-degree atrioventricular block in fetus: natural history and predictive factors for spontaneous recovery.

OBJECTIVES: To uncover the clinical course of fetal isolated non-immune mediated second-degree AVB and determine the factors associated with the spontaneous recovery for fetal non-immune second-degree atrioventricular block (AVB). METHODS: A total of 20 fetuses with isolated, non-immune mediated second-degree AVB were prospectively recruited between 2014 and 2022. These fetuses were divided into the spontaneous recovery group (n=12) and the non-spontaneous recovery group (n=8). Maternal and fetal basic characteristics, intrauterine and postnatal outcomes were compared between groups. RESULTS: Twelve fetuses restored 1:1 atrioventricular conduction in utero and did not recur during the postnatal follow-up period. The residual eight fetuses maintained as second-degree AVB and six of them were aborted due to parental request in utero. Of the two live children with second-degree AVB, one of them progressed to complete AVB at the latest follow up at the age of 34 months, but without any symptoms, heart enlargement or dysfunction. The residual one progressed to complete AVB and was finally diagnosed with type 2 long-QT syndrome. Fetuses in the spontaneous recovery group presented with earlier gestational age at diagnosis (20.0[17.0-26.0] vs. 24.5[18.0-35.0] weeks, p=0.004) and higher atrial rate (147[130-160] vs 138.00[125.00-149.00] bpm, p=0.006) in comparison with the non-spontaneous recovery group. A cut-off value of 22.5 weeks of gestational age and 144 bpm of atrial rate at diagnosis could predict the failure of spontaneous recovery, with sensitivities of 87.5%, 75%, and specificities of 92.0%, 87.5%, respectively. CONCLUSIONS: The outcome of fetal non-immune second-degree AVB was favorable. Earlier gestational age at diagnosis and higher atrial rate were related to spontaneous reversion for isolated non-immune-mediated second-degree AVB. However, prenatal gene test should be performed for those with persistent AVB to exclude the heritable disorders including LQTS. These findings may provide important references for clinical management and prenatal counseling. This article is protected by copyright. All rights reserved.

[Respiratory virus infection and its influence on outcome in children with septic shock].

Objective: To investigate respiratory virus infection in children with septic shock in pediatric care units (PICU) in China and its influence on clinical outcomes. Methods: The clinical data of children with septic shock in children's PICU from January 2018 to December 2019 in 10 Chinese hospitals were retrospectively collected. They were divided into the pre-COVID-19 and post-COVID-19 groups according to the onset of disease, and the characteristics and composition of respiratory virus in the 2 groups were compared. Matching age, malignant underlying diseases, bacteria, fungi and other viruses, a new database was generated using 1∶1 propensity score matching method. The children were divided into the respiratory virus group and non-respiratory virus group according to the presence or absence of respiratory virus infection; their clinical characteristics, diagnosis, and treatment were compared by t-test, rank sum test and Chi-square test. The correlation between respiratory virus infection and the clinical outcomes was analyzed by logistic regression. Results: A total of 1 247 children with septic shock were included in the study, of them 748 were male; the age was 37 (11, 105) months. In the pre-and post-COVID-19 groups, there were 530 and 717 cases of septic shock, respectively; the positive rate of respiratory virus was 14.9% (79 cases) and 9.8% (70 cases); the seasonal distribution of septic shock was 28.9% (153/530) and 25.9% (185/717) in autumn, and 30.3% (161/530) and 28.3% (203/717) in winter, respectively, and the corresponding positive rates of respiratory viruses were 19.6% (30/153) and 15.7% (29/185) in autumn, and 21.1% (34/161) and 15.3% (31/203) in winter, respectively. The positive rates of influenza virus and adenovirus in the post-COVID-19 group were lower than those in the pre-COVID-19 group (2.1% (15/717) vs. 7.5% (40/530), and 0.7% (5/717) vs. 3.2% (17/530), χ2=21.51 and 11.08, respectively; all P<0.05). Rhinovirus virus were higher than those in the pre-Covid-19 group (1.7% (12/717) vs. 0.2% (1/530), χ2=6.51, P=0.011). After propensity score matching, there were 147 cases in both the respiratory virus group and the non-respiratory virus group. Rate of respiratory failure, acute respiratory distress, rate of disseminated coagulation dysfunction, and immunoglobulin usage of the respiratory virus group were higher than those of non-respiratory virus group (77.6% (114/147) vs. 59.2% (87/147), 17.7% (26/147) vs. 4.1% (6/147), 15.6% (25/147) vs. 4.1% (7/147), and 35.4% (52/147) vs. 21.4% (32/147); χ2=11.07, 14.02, 11.06 and 6.67, all P<0.05); and PICU hospitalization of the former was longer than that of the later (7 (3, 16) vs. 3 (1, 7)d, Z=5.01, P<0.001). Univariate logistic regression analysis showed that the presence of respiratory viral infection was associated with respiratory failure, disseminated coagulation dysfunction, the use of mechanical ventilation, and the use of immunoglobulin and anti-respiratory viral drugs (OR=2.42, 0.22, 0.25, 0.56 and 1.12, all P<0.05). Conclusions: The composition of respiratory virus infection in children with septic shock is different between pre and post-COVID-19. Respiratory viral infection is associated with organ dysfunction in children with septic shock. Decreasing respiratory viral infection through respiratory protection may improve the clinical outcome of these children.

[The application of full-length urethral preservation without anastomosis in single-port laparoscopic radical prostate cancer].

Objective: To preliminarily examine the feasibility and outcome of single-port laparoscopic radical prostatectomy with full-length urethral preservation (FLUP-SPRP). Method: This study was a prospective case series study. A total of 25 patients with prostate cancer who met the enrollment criteria and agreed to this surgical procedure from March 2022 to December 2022 were collected at the Department of Urology, the Second Affiliated Hospital of Nanjing Medical University. The age of the patients was (67.2±7.6) years (range: 61 to 76 years). This novel procedure was performed by an experienced surgeon who performed single hole radical prostatectomy skillfully. Patient urinary control, tumor control, and related surgical complications after surgery were regularly monitored. Postoperative urinary control was evaluated using the daily amount of urine pad, 0 to 1 piece of urine pad was to restore urinary control, and 0 to 1 piece of pad within 24 hours after catheter removal was immediate urinary control. Result: All prodecures were successfully completed without transit to open surgery. The surgical time was (128.4±22.4) minutes (range: 100 to 145 minutes), the intraoperative blood loss was (68.2±13.7) ml (range: 50 to 120 ml). The urethral injury occurred in 4 cases during surgery and was repaired by sutures. The urinary control recovery rates within 24 hours, 1 week, 4 weeks, and 7 weeks after surgery were 80.0%, 84.0%, 92.0% and 100%, respectively. Postoperative large section pathology revealed 1 case with a positive basal margin of the prostate and negative margins of all prostate glands around the urethra. Postoperative complications included urinary tract infection in 3 cases, urodynia in 2 cases, and acute urinary retention in 1 case. MRI follow-up 3 months after surgery showed normal anatomy of the bladder and urethra. The follow-up values of prostate specific antigen at 3 and 6 months after surgery were less than 0.1 µg/L. Conclusions: The preliminary results of this study indicate that the FLUP-SPRP procedure is safe and feasible. The early results of postoperative urinary control and oncology are as expected.

[HVPG minimally invasive era: exploration based on forearm venous approach].

Objective: The transjugular or transfemoral approach is used as a common method for hepatic venous pressure gradient (HVPG) measurement in current practice. This study aims to confirm the safety and effectiveness of measuring HVPG via the forearm venous approach. Methods: Prospective recruitment was conducted for patients with cirrhosis who underwent HVPG measurement via the forearm venous approach at six hospitals in China and Japan from September 2020 to December 2020. Patients' clinical baseline information and HVPG measurement data were collected. The right median cubital vein or basilic vein approach for all enrolled patients was selected. The HVPG standard process was used to measure pressure. Research data were analyzed using SPSS 22.0 statistical software. Quantitative data were used to represent medians (interquartile ranges), while qualitative data were used to represent frequency and rates. The correlation between two sets of data was analyzed using Pearson correlation analysis. Results: A total of 43 cases were enrolled in this study. Of these, 41 (95.3%) successfully underwent HVPG measurement via the forearm venous approach. None of the patients had any serious complications. The median operation time for HVPG detection via forearm vein was 18.0 minutes (12.3~38.8 minutes). This study confirmed that HVPG was positively closely related to Child-Pugh score (r = 0.47, P = 0.002), albumin-bilirubin score (r = 0.37, P = 0.001), Lok index (r = 0.36, P = 0.02), liver stiffness (r = 0.58, P = 0.01), and spleen stiffness (r = 0.77, P = 0.01), while negatively correlated with albumin (r = -0.42, P = 0.006). Conclusion: The results of this multi-centre retrospective study suggest that HVPG measurement via the forearm venous approach is safe and feasible.

[Research on quantitative evaluation of revise requirements of Specifications of Air Sampling for Hazardous Substances Monitoring in the Workplace (GBZ 159-2004)].

Objective: To conduct quantitative evaluation on the revise requirements of Specifications of Air Sampling for Hazardous Substances Monitoring in the Workplace (GBZ 159-2004) , clarify the problems and suggestions during its implementation for improvement, and provide a basis for the revision of the standard. Methods: From April to September 2021, stratified convenient sampling method was adopted and semi-open questionnaire was used to investigate the occupational health personnel in CDC, occupational prevention and control institutes, employers, third-party technical service institutions and universitie. The entropy weight of each index and the score based on entropy weight of GBZ 159 were calculated. Spearman rank correlation analysis was used to describe the correlation between the two indexes and radar chart was drawn for comprehensive evaluation. Results: A total of 151 questionnaires were received from the respondents, of which 147 were valid, with an effective recovery rate of 97.35%, involving 29 provinces, autonomous regions and municipalities. The median G scores of the necessity and urgency of GBZ 159 revision based on entropy weight were 2.84 and 3.17, respectively, and the difference was statistically significant (M=-25.50, P<0.001) . The trend of the score G of necessity and urgency based on entropy weight was basically the same for all secondary items (r(s)=0.9998, P<0.001) , and the score G of urgency based on entropy weight was higher than that of necessity. The highest score G of necessity and urgency based on entropy weight was "3.13 long time sampling", which were 7.56 and 8.23 respectively. This was followed by "3.12 short time sampling", which were 7.19 and 7.13 respectively. Conclusion: GBZ 159 has encountered some new problems and challenges in the implementation process, and some of its technical indicators have been out of line with the actual practice of occupational health at present. These are the two items that urgently needs to be revised and improved, such as "3.13 long time sampling" and "3.12 short time sampling" and other items need to be revised and improved.

[Comparison and analysis research on occupational exposure limits of coal dust between China and foreign countries].

Objective: To study and compare the occupational exposure limits (OELs) of coal dust between China and foreign countries, understand the OEL of coal dust in China, and provide data and basis for revising the OEL of coal dust in China. Methods: In August 2023, by searching the official websites of limits setting institutions in relevant countries and regions at home and abroad, collecting and sorting out the OELs of coal dust issued by 10 limit setting institutions in 6 countries and the background information of the formulation, and conducting specific analysis on the classification, limit level and formulation principles of coal dust OEL in each country/institution. Results: In China and Japan, the total dust and respirable dust of coal dust OEL were established respectively, while in other countries, only the time-weighted average concentration (TWA) of respirable coal dust exposure was established. The TWA prescribed by China's Notional Health Commission, the United States Occupational Safety and Health Administration (OSHA) , the United States Mining Safety and Health Administration (MSHA) and the Australian Safety Work Bureau when the SiO(2) content was less than 5% were 5, 2.4, 2 and 3 mg/m(3) respectively. China GBZ 2.1-2019 sets the limit of 2.5 mg/m(3) for respirable coal dust with SiO(2) content less than 10%. The TWA set by the American Conference of Government Industrial Hygienists (ACGIH) and the South African Department of Mines and Energy (DME) for anthracite coal were 0.4 and 0.8 mg/m(3), respectively, and bituminous coal or lignite were 0.9 and 1.8 mg/m(3), respectively. The respirable coal dust TWA set by the National Institute for Occupational Safety and Health (NIOSH) in the United States was 1 mg/m(3), and the TWA set by the New Zealand Work Safety Authority was 3 mg/m(3). Conclusion: At present, the OEL of coal dust in China is at a relatively loose level, and it is suggested to further explore the possibility of revising coal dust OEL.

[Study on the implementation effect evaluation of Specifications of Air Sampling for Hazardous Substances Monitoring in the Workplace (GBZ 159-2004)].

Systematically evaluate the implementation of Specifications of Air Sampling for Hazardous Substances Monitoring (GBZ 159-2004) , so as to provide technical basis for the future standard revision. The semi-structured interview method was used to interview the industry experts from centers for disease control and prevention, occupational disease prevention and control hospitals/institutes, employers, third-party technical service institutions and universities, and the induction method was used to refine the topics and relevant suggestions. Some technical indicators of GBZ 159 are not suitable for the current actual work of occupational health, and need to be revised and improved urgently. The revised GBZ 159 should comply with the current situation of China's industrial development and the development of occupational health testing equipment in the new era, and improve the relevant technical requirements of sampling quality control.

[Introduction to carcinogenesis of nickel compounds in ILO criteria for Diagnosis and Exposure Standard for Occupational Diseases].

International Agency for Research on Cancer (IARC) classifies nickel compounds as Class Ⅰ carcinogens. International Labour Organization (ILO) also lists nickel compounds as carcinogenic factors of occupational cancer. At present, China is revising the Classification and Catalogue of Occupational Diseases, and cancer caused by nickel compounds may also be included in the statutory occupational diseases. The Diagnostic and Exposure Standards for Occupational Diseases published by ILO in 2022 discussed the pathogenic characteristics, occupational exposure, main health effects, diagnostic criteria and key preventive measures of nickel compounds in detail. This article mainly introduces its contents, in order to provid a basis for the formulation of relevant standards in China.

Evaluation of factors associated with high advanced HIV disease and mortality in Southwestern China: a retrospective cohort study, 2005-2020.

OBJECTIVES: To assess the prevalence, all-cause mortality and determinants of advanced HIV disease (AHD) or severe immunosuppression (SIS) in the rural-urban communities of Southwestern China. STUDY DESIGN: Retrospective cohort study. METHOD: Data on HIV/AIDS cases reported in 2005-20 were collected from Case Report System. A binary logistic regression model assessed the risk factors of AHD/SIS prevalence. Survival curves across rural-urban regions were compared using Kaplan-Meier estimates and log-rank tests. Determinants of all-cause mortality were identified using the Cox proportional hazard model. RESULTS: Among 14,533 newly diagnosed HIV/AIDS patients, 7497 (51.6%) presented with AHD and 2564 (17.6%) with SIS. Compared with urban patients, rural patients had a higher prevalence of AHD (56.7% vs 40.7%) and SIS (20.1% vs 12.4%), all-cause mortality (AHD 12.3 vs 5.6, SIS 16.3 vs 5.5, per 100 person-years). Their 5-year survival probability (AHD 59.5% vs 77.1%; SIS 54.4% vs 76.3%) and mean survival time (AHD 106.5 vs 140.6 months, SIS 95.3 vs 144.2 months, p < 0.0001) were lower. Rural patients had an increased risk of SIS prevalence (adjusted odds ratios 1.45, 95% confidence interval [CI] 1.28-1.64; p < 0.0001) and mortality of the total cohort (adjusted hazard ratios 1.41, 95% CI 1.29-1.55; p < 0.0001), AHD cohort (1.38, 1.24-1.54; p < 0.0001), and SIS cohort (1.49, 1.23-1.81; p < 0.0001). CONCLUSIONS: A high prevalence of AHD/SIS was a severe phenomenon that caused high mortality in rural areas. A regional point-of-care strategy targeting AHD/SIS detection and management is essential for reducing the mortality risk.

[Overexpression of LncRNA MEG3 promotes ferroptosis and enhances chemotherapy sensitivity of hepatocellular carcinoma cells to cisplatin].

OBJECTIVE: To investigate the effect of overexpression of LncRNA MEG3 on proliferation, migration and cisplatin sensitivity of hepatoma cells HepG2 and LM3 and explore the underlying and mechanism. METHODS: The expression of MEG3 in healthy individuals and patients with hepatocellular carcinoma (HCC) was analyzed by online bioinformatics analysis, and Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect MEG3 expression in different HCC cell lines. A MEG3-overexpresing plasmid was transfected in HepG2 and LM3 cells, and the changes in cell proliferation and migration were examined using CCK8 assay and scratch assay. CCK8 assay was used to determine the inhibitory rate of cisplatin on the transfected cells. A reactive oxygen species (ROS) fluorescence probe (DCFH-DA) and malondialdehyde (MDA) kit were used to assess the changes in ROS production and MDA level in the cells. Western blotting was performed to detect the expression levels of ferroptosis-related proteins glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1). RESULTS: The expression of MEG3 was significantly lower in HCC cells than in LO2 cells, which was consistent with the results of bioinformatic analysis (P < 0.05). Overexpression of MEG3 in the HCC cell lines significantly suppressed cell proliferation and migration (P < 0.05), increased the cell inhibition rate of cisplatin (P < 0.05), enhanced cellular ROS production and increased MDA levels in the cells (P < 0.05). MEG3 overexpression significantly decreased the expressions of GPX4 and FTH1 in the HCC cell lines. CONCLUSION: The expression of MEG3 is decreased in HCC cells, and its overexpression inhibits proliferation and migration and enhances cisplatin sensitivity of HCC cells by promoting ferroptosis of the cells.

[Clinical analysis of lung adenocarcinoma with epidermal growth factor receptor mutation transformed into sarcoma].

Objective: To analyze the clinical data of a case of lung adenocarcinoma with Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) resistance transforming into sarcoma, and to conduct a literature review to improve the understanding of the resistance mechanism. Histological transformation is a unique form of acquired resistance of EGFR-TKIs in non-small cell lung cancer (NSCLC). Thereinto, the transformation of small cell carcinoma is more common, and the transformation of sarcoma is rarely reported. Methods: Clinicopathological data on the treatment process, pathological features, and clinical outcome of the patient with EGFR-TKIs-resistance lung adenocarcinoma transforming into sarcoma were collected. The literature was reviewed to analyze the pathogenetic mechanism for sarcomatoid carcinoma or sarcoma transformation after drug resistance of adenocarcinoma, as well as the clinical characteristics of the patients and the corresponding therapeutic schemes. Results: We reported a patient with lung adenocarcinoma who developed EGFR-T790M mutation after first-line treatment with icotinib and sarcoma transformation after second-line treatment with almonertinib. Chemotherapy, radioactive particle implantation, antiangiogenic therapy and immunotherapy were followed, but the results were unsatisfactory. There was no report of EGFR-TKIs-resistant lung adenocarcinoma transforming into sarcoma. Among the 14 reports of adenocarcinoma transforming into sarcomatoid carcinoma, 8 cases had EGFR mutation, 3 cases had ALK mutation, 2 cases had ROS1 mutation, and 1 case had no asscoiated sensitive mutation. The median survival of 14 patients with adenocarcinoma transforming to sarcomatoid carcinoma was only 3 months. Conclusions: Sarcoma transformation can be one of the forms of drug resistance in patients with lung adenocarcinoma with EGFR-TKIs. The prognosis of patients with adenocarcinoma after transformation into sarcoma is poor.

Clinically Oriented CBCT Periapical Lesion Evaluation via 3D CNN Algorithm.

Apical periodontitis (AP) is one of the most prevalent disorders in dentistry. However, it can be underdiagnosed in asymptomatic patients. In addition, the perioperative evaluation of 3-dimensional (3D) lesion volume is of great clinical relevance, but the required slice-by-slice manual delineation method is time- and labor-intensive. Here, for quickly and accurately detecting and segmenting periapical lesions (PALs) associated with AP on cone beam computed tomography (CBCT) images, we proposed and geographically validated a novel 3D deep convolutional neural network algorithm, named PAL-Net. On the internal 5-fold cross-validation set, our PAL-Net achieved an area under the receiver operating characteristic curve (AUC) of 0.98. The algorithm also improved the diagnostic performance of dentists with varying levels of experience, as evidenced by their enhanced average AUC values (junior dentists: 0.89-0.94; senior dentists: 0.91-0.93), and significantly reduced the diagnostic time (junior dentists: 69.3 min faster; senior dentists: 32.4 min faster). Moreover, our PAL-Net achieved an average Dice similarity coefficient over 0.87 (0.85-0.88), which is superior or comparable to that of other existing state-of-the-art PAL segmentation algorithms. Furthermore, we validated the generalizability of the PAL-Net system using multiple external data sets from Central, East, and North China, showing that our PAL-Net has strong robustness. Our PAL-Net can help improve the diagnostic performance and speed of dentists working from CBCT images, provide clinically relevant volume information to dentists, and can potentially be applied in dental clinics, especially without expert-level dentists or radiologists.

[Association between hair trace element and all-cause death in elderly people in Hainan].

Objective: To explore the association between hair trace element and all-cause death in the elderly in Hainan Province. Methods: The subjects of the study were elderly people from China Hainan Centenarian Cohort Study, a total of 163 elderly were included. The association between hair trace element level and all-cause death was analyzed by using Cox proportional risk regression model. Results: After fully adjusting the covariates, the multiple Cox proportional hazards regression analyses showed that selenium (Se), manganese (Mn), strontium (Sr) concentrations in hair were significantly associated with all-cause mortality, the hazard ratio (HR) were 0.72 (95%CI: 0.54-0.98, P=0.035), 1.50 (95%CI: 1.07-2.11, P=0.020) and 0.54 (95%CI: 0.37-0.79, P=0.001), respectively. Subgroup and cross analysis showed that hair copper (Cu) were significant association with death in the people with anemia, the HR were 1.81 (95%CI: 1.13-2.88, P=0.013). And, hair Mn interacted with anemia, the HR was 0.46 (95%CI: 0.22-0.94, P=0.033). Conclusions: Se, Mn and Sr concentrations in hair were associated with the elevated risk for all-cause death in the elderly in Hainan. Se, Mn and Sr concentrations in hair can be used as a reference index for the prediction of the death risk of long-lived elderly in community, suggesting that the daily diet of elderly people are rich and diverse, in order to maintain normal and balanced trace element content in the body.

[HIF-1α activation induces cholesterol homeostasis dysfunction to accelerate progression of diabetic nephropathy in rats].

OBJECTIVE: To investigate the effect of hypoxia inducible factor-1α (HIF-1α) activation on cholesterol homeostasis dysfunction in diabetic nephropathy (DN). METHODS: Rat models of type 1 diabetes established by intraperitoneal STZ injection were treated with intraperitoneal injection of Lificiguat (YC-1, a HIF-1α inhibitor). Human proximal tubular cell line HK-2 was incubated with cobalt chloride (CoCl2, 100 µmol/L) in the presence or absence of 30 mmol/L glucose for 24 h. Renal injury of the rats was assessed by measuring 24-h urinary total protein level and PAS staining of the renal tubules. Cholesterol deposition in rat kidneys and HK-2 cells were observed using a quantitative assay of total cholesterol and Filipin staining, and HIF-1α protein expression was detected using Western blotting, immunohistochemistry or immunofluorescence assay; the expressions of cholesterol metabolism-related proteins HMGCR, LDLr, CXCL16 and profibrogenic factors including TGF-ß1 and CTGF were also analyzed. RESULTS: The diabetic rats showed significantly increased 24-h urinary protein level (P<0.001), obvious renal tubular injury, and increased renal cholesterol content (P<0.05) with significantly increased HIF-1α expression in the renal tubular (P<0.01). YC-1 treatment significantly ameliorated tubulointerstitial injury in the diabetic rats as shown by decreased 24-h urinary total protein (P<0.05) and reduced damage area of the tubules, and effectively decreased renal cholesterol levels and renal expression of HIF-1α (P<0.05). In HK-2 cells, CoCl2 stimulation in the presence of high glucose effectively activated HIF-1α expression (P<0.0001), aggravated cholesterol accumulation (P<0.05), and increased the expressions of HMGCR, LDLr, CXCL16, TGF-ß1, and CTGF (P<0.05 or 0.01). Consistent with the in vitro study, YC-1 treatment also significantly decreased the expressions of cholesterol metabolism-related proteins and the profibrogenic factors in the renal tubules of the diabetic rats. CONCLUSION: HIF-1α activation induces cholesterol homeostasis dysregulation possibly by upregulating the de novo synthesis and uptake of cholesterol, thereby aggravating tubulointerstitial injury in DN.

[Analysis of late-diagnosis and associated factors in newly reported HIV infections among men who have sex with men in Guangxi Zhuang Autonomous Region, 2005-2021].

Objective: To analyze the trend of late-diagnosis of HIV-infected men who have sex with men (MSM) before and after the AIDS Conquering Project in Guangxi Zhuang Autonomous Region (Guangxi) and its influencing factors, in order to find out the population groups that need priority intervention at the present stage. Methods: The HIV-infected MSM in Guangxi from 2005-2021 were selected from the National Integrated HIV/AIDS Control and Prevention Data System. The Joinpoint 4.9.1.0 software was used to test the time trend of late-diagnosis and non-late-diagnosis cases, and logistic regression was applied to analyze the factors influencing the proportion of late-diagnosis at each stage. Results: From 2005 to 2021, 5 764 HIV-infected MSM were reported in Guangxi from 2005 to 2021, with an overall late-diagnosis of 28.45% (1 640 cases). Under the 2015 baseline data as the boundary, the proportion of late-diagnosis cases showed a trend of sharp decline followed by stabilization from 2005 to 2015, average annual percent change= -6.90% (P<0.001). The effect of factors such as resident population, occupation as a farmer or worker, and sample originating from medical consultation on late-diagnosis changed considerably before and after the implementation of the project, and the factors influencing late-diagnosis at this stage were age, resident population, occupation as a farmer, worker or student. The factors influencing late-diagnosis at this stage are age, resident population, and occupation as a farmer, worker and a student. Conclusions: The proportion of late diagnosis cases of HIV-infected MSM in Guangxi decreased significantly before and after the project. However, late-diagnosis should not be neglected and precise prevention and control should be carried out for the resident population, farmers, workers or students.

[The application of ultrasound in the diagnosis of small bowel volvulus in adults].

Objective: To analyze the ultrasound characteristics of small bowel volvulus among adults and to investigate the value of ultrasound in the diagnosis of small bowel volvulus. Methods: Totally 34 adults with small bowel volvulus confirmed by clinical diagnosis or surgery and who underwent ultrasound examination at Peking Union Medical College Hospital from August 2017 to October 2022 were enrolled, including 19 males and 15 females, aged (55.0±21.8) years (range: 19 to 94 years). The clinical characteristics, CT images and ultrasound images of the patients were retrospectively reviewed, and the ultra, sound features of small bowel volvulus and its diagnostic efficacy were analyzed. Results: Abdominal pain was the typical clinical symptom of all patients. Other symptoms included 21 cases of abdominal distension, 19 cases of nausea and vomiting, and 13 cases of cessation of passage of stool or flatus. Eight patients had signs of peritonitis and 22 patients had abnormal bowel sounds. Twenty patients had a history of abdominal surgery. Twenty-seven patients underwent surgery for intestinal obstruction, and the remaining 7 patients improved after conservative treatment. All cases were evaluated by ultrasound, 11 cases showed a "whirl sign" and were diagnosed as small bowel volvulus, the diagnostic accuracy rate was 32.4% (11/34), ultrasound simultaneously diagnosed intestinal obstruction in 21 cases, 17 cases of abdominal effusion, 4 cases of intestinal wall thickening, 2 cases of abdominal mass, 1 case of intussusception, 1 case of right sided inguinal hernia. CT and ultrasound had a consistent positive discovery in 88.2% (30/34) of all the patients. Conclusion: Ultrasound is valuable in the diagnosis of small bowel volvulus and the evaluation of complications.

[Association analysis between sex hormone levels and all-cause mortality in Hainan female centenarians].

Objective: To investigate the distribution characteristics of sex hormones and their relationship with all-cause mortality in Hainan female centenarians. Methods: All the subjects were from China Hainan Centenarian Cohort Study. A total of 717 female centenarians were included in the final analysis. Kaplan-Meier method was used to draw the survival curve, and Cox proportional hazard regression was used to analyze the relationship between sex hormones and survival time. Results: The M(Q1, Q3) of estradiol and progesterone among female centenarians was 32.60 (18.40, 58.70) pmol/L and 0.62 (0.32, 1.01) nmol/L. The estradiol (pmol/L) and progesterone (nmol/L) in the survival and death groups were 26.65 vs.37.80, 0.54 vs.0.69, respectively, with statistical differences (P<0.05). Cox multivariate analysis showed that estradiol and progesterone were significantly associated with death (P<0.05), the hazard ratio (HR) of estradiol Q4 was 1.58 (95%CI: 1.17-2.15), and the HR of progesterone Q3 was 1.53 (95%CI: 1.10-2.12), HR for Q4 was 1.63 (95%CI: 1.15-2.32). Subgroup and cross-analysis showed that estradiol was statistically significant with hypertension, diabetes, and low high-density lipoprotein cholesterol (P<0.05), and progesterone interacted with diabetes (P=0.016), while testosterone interacted with low high-density lipoprotein cholesterol (P=0.034). Conclusion: It is suggested that the estrogen levels of female centenarians in Hainan were associated with a higher mortality risk and an increased risk of cardiovascular metabolic disease (such as diabetes, hypertension, and abnormal lipid metabolism).