Analysis of gut microecological characteristics and differences between children with biliary atresia and non-biliary atresia in infantile cholestasis.

Introduction: In infants with cholestasis, variations in the enterohepatic circulation of bile acids and the gut microbiota (GM) characteristics differ between those with biliary atresia (BA) and non-BA, prompting a differential analysis of their respective GM profiles. Methods: Using 16S rDNA gene sequencing to analyse the variance in GM composition among three groups: infants with BA (BA group, n=26), non-BA cholestasis (IC group, n=37), and healthy infants (control group, n=50). Additionally, correlation analysis was conducted between GM and liver function-related indicators. Results: Principal component analysis using Bray-Curtis distance measurement revealed a significant distinction between microbial samples in the IC group compared to the two other groups. IC-accumulated co-abundance groups exhibited positive correlations with aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, and total bile acid serum levels. These correlations were notably reinforced upon the exclusion of microbial samples from children with BA. Conclusion: The varying "enterohepatic circulation" status of bile acids in children with BA and non-BA cholestasis contributes to distinct GM structures and functions. This divergence underscores the potential for targeted GM interventions tailored to the specific aetiologies of cholestasis.

Selective Oxidation of Vitamin D3 Enhanced by Long-Range Effects of a Substrate Channel Mutation in Cytochrome P450BM3 (CYP102A1).

Vitamin D deficiency affects nearly half the population, with many requiring or opting for supplements with vitamin D3(VD3), the precursor of vitamin D (1α,25-dihydroxyVD3). 25-HydroxyVD3, the circulating form of vitamin D, is a more effective supplement than VD3 but its synthesis is complex. We report here the engineering of cytochrome P450BM3(CYP102A1) for the selective oxidation of VD3 to 25-hydroxyVD3. Long-range effects of the substrate-channel mutation Glu435Ile promoted binding of the VD3 side chain close to the heme, enhancing VD3 oxidation activity that reached 6.62 g of 25-hydroxyVD3 isolated from a 1-litre scale reaction (69.1% yield; space-time-yield 331 mg/L/h).

NOX4-mediated astrocyte ferroptosis in Alzheimer's disease.

This study investigates NADPH oxidase 4 (NOX4) involvement in iron-mediated astrocyte cell death in Alzheimer's Disease (AD) using single-cell sequencing data and transcriptomes. We analyzed AD single-cell RNA sequencing data, identified astrocyte marker genes, and explored biological processes in astrocytes. We integrated AD-related chip data with ferroptosis-related genes, highlighting NOX4. We validated NOX4's role in ferroptosis and AD in vitro and in vivo. Astrocyte marker genes were enriched in AD, emphasizing their role. NOX4 emerged as a crucial player in astrocytic ferroptosis in AD. Silencing NOX4 mitigated ferroptosis, improved cognition, reduced Aß and p-Tau levels, and alleviated mitochondrial abnormalities. NOX4 promotes astrocytic ferroptosis, underscoring its significance in AD progression.

YOLO SSPD: a small target cotton boll detection model during the boll-spitting period based on space-to-depth convolution.

Introduction: Cotton yield estimation is crucial in the agricultural process, where the accuracy of boll detection during the flocculation period significantly influences yield estimations in cotton fields. Unmanned Aerial Vehicles (UAVs) are frequently employed for plant detection and counting due to their cost-effectiveness and adaptability. Methods: Addressing the challenges of small target cotton bolls and low resolution of UAVs, this paper introduces a method based on the YOLO v8 framework for transfer learning, named YOLO small-scale pyramid depth-aware detection (SSPD). The method combines space-to-depth and non-strided convolution (SPD-Conv) and a small target detector head, and also integrates a simple, parameter-free attentional mechanism (SimAM) that significantly improves target boll detection accuracy. Results: The YOLO SSPD achieved a boll detection accuracy of 0.874 on UAV-scale imagery. It also recorded a coefficient of determination (R2) of 0.86, with a root mean square error (RMSE) of 12.38 and a relative root mean square error (RRMSE) of 11.19% for boll counts. Discussion: The findings indicate that YOLO SSPD can significantly improve the accuracy of cotton boll detection on UAV imagery, thereby supporting the cotton production process. This method offers a robust solution for high-precision cotton monitoring, enhancing the reliability of cotton yield estimates.

Backwater makes the tributaries of large river becoming phosphorus "sink".

The complex hydrological conditions caused by the backwater effect at the confluence inevitably modify the geochemical processes of elements. However, there is still a lack of comprehensive understanding regarding the precise transformation mechanisms of nutrients in large river systems. This study aimed to investigate the hydrodynamic characteristics and their impact on phosphorus transfer in the lower Han River, which is influenced by backwater from the Yangtze River (the largest river in China). By establishing a hydrodynamic-water quality model, we have determined that the discharge ratio (the ratio of flow between the Han River discharge and the Yangtze River discharge) can be utilized as a representative indicator of the backwater effect from the Yangtze River on the Han River. Three distinct patterns were identified in this study: mixing, backwater, and intrusion. The corresponding discharge ratio values were categorized as >0.08, 0.01∼0.08, and <0.01 respectively. Additionally, the extent of the backwater zone was determined, revealing that the length of the backwater zone increased from 50 km (XG) to 100 km (FS) as the discharge ratio decreased from 0.08 to 0.01. Furthermore, it was observed that the water level at the confluence rose from 2.52 m to 6.83 m in accordance with these changes in discharge ratio values. The migration pattern of phosphorus primarily involved the settling and retention of particulate phosphorus, particularly the labile particulate organic phosphorus (LOP) and dissolved organic phosphorus (DOP). When the confluent patterns became the intrusion pattern, the backwater zone expanded to 150 m (XT), causing a 10.40 m increase in water level at the confluence. An intrusion zone formed, and its phosphorus concentrations were same as Yangtze River's. Above the intrusion area, a backwater region formed and its concentrations of LOP and DOP decreased, while the concentration of PO43- increased due to the release from resuspended particles. This release was induced by higher velocity of bottom water brought about by the water exchange of two rivers. The discharge ratio of 0.01-0.08 resulted in the sedimentation of LOP and DOP, causing the lower Han River to act as a "sink" for phosphorus, potentially exacerbating phosphorus pollution. Higher discharge ratios in spring led to phosphorus release from sediment, increasing dissolved phosphorus concentrations and raising the risk of algal blooms in the lower Han River. These findings have significant implications for larger rivers worldwide and provide insights into strategies for ecological management and prevention of algal blooms.

Mapping the distribution of Nipah virus infections: a geospatial modelling analysis.

BACKGROUND: Nipah virus is a zoonotic paramyxovirus responsible for disease outbreaks with high fatality rates in south and southeast Asia. However, knowledge of the potential geographical extent and risk patterns of the virus is poor. We aimed to establish an integrated spatiotemporal and phylogenetic database of Nipah virus infections in humans and animals across south and southeast Asia. METHODS: In this geospatial modelling analysis, we developed an integrated database containing information on the distribution of Nipah virus infections in humans and animals from 1998 to 2021. We conducted phylodynamic analysis to examine the evolution and migration pathways of the virus and meta-analyses to estimate the adjusted case-fatality rate. We used two boosted regression tree models to identify the potential ecological drivers of Nipah virus occurrences in spillover events and endemic areas, and mapped potential risk areas for Nipah virus endemicity. FINDINGS: 749 people and eight bat species across nine countries were documented as being infected with Nipah virus. On the basis of 66 complete genomes of the virus, we identified two clades-the Bangladesh clade and the Malaysia clade-with the time of the most recent common ancestor estimated to be 1863. Adjusted case-fatality rates varied widely between countries and were higher for the Bangladesh clade than for the Malaysia clade. Multivariable meta-regression analysis revealed significant relationships between case-fatality rate estimates and viral clade (p=0·0021), source country (p=0·016), proportion of male patients (p=0·036), and travel time to health-care facilities (p=0·036). Temperature-related bioclimate variables and the probability of occurrence of Pteropus medius were important contributors to both the spillover and the endemic infection models. INTERPRETATION: The suitable niches for Nipah virus are more extensive than previously reported. Future surveillance efforts should focus on high-risk areas informed by updated projections. Specifically, intensifying zoonotic surveillance efforts, enhancing laboratory testing capacity, and implementing public health education in projected high-risk areas where no human cases have been reported to date will be crucial. Additionally, strengthening wildlife surveillance and investigating potential modes of transmission in regions with documented human cases is needed. FUNDING: The Key Research and Development Program of China.

An novel effective and safe model for the diagnosis of nonalcoholic fatty liver disease in China: gene excavations, clinical validations, and mechanism elucidation.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. NAFLD leads to liver fibrosis and hepatocellular carcinoma, and it also has systemic effects associated with metabolic diseases, cardiovascular diseases, chronic kidney disease, and malignant tumors. Therefore, it is important to diagnose NAFLD early to prevent these adverse effects. METHODS: The GSE89632 dataset was downloaded from the Gene Expression Omnibus database, and then the optimal genes were screened from the data cohort using lasso and Support Vector Machine Recursive Feature Elimination (SVM-RFE). The ROC values of the optimal genes for the diagnosis of NAFLD were calculated. The relationship between optimal genes and immune cells was determined using the DECONVOLUTION algorithm CIBERSORT. Finally, the specificity and sensitivity of the diagnostic genes were verified by detecting the expression of the diagnostic genes in blood samples from 320 NAFLD patients and liver samples from 12 mice. RESULTS: Through machine learning we identified FOSB, GPAT3, RGCC and RNF43 were the key diagnostic genes for NAFLD, and they were further demonstrated by a receiver operating characteristic curve analysis. We found that the combined diagnosis of the four genes identified NAFLD samples well from normal samples (AUC = 0.997). FOSB, GPAT3, RGCC and RNF43 were strongly associated with immune cell infiltration. We also experimentally examined the expression of these genes in NAFLD patients and NAFLD mice, and the results showed that these genes are highly specific and sensitive. CONCLUSIONS: Data from both clinical and animal studies demonstrate the high sensitivity, specificity and safety of FOSB, GPAT3, RGCC and RNF43 for the diagnosis of NAFLD. The relationship between diagnostic key genes and immune cell infiltration may help to understand the development of NAFLD. The study was reviewed and approved by Ethics Committee of Tianjin Second People's Hospital in 2021 (ChiCTR1900024415).

Mitochondrial biological function and risk of atrial fibrillation and atrial flutter: A 2-sample Mendelian randomization study.

Current research suggests that mitochondrial dysfunction can be a contributing factor in the development of cardiac arrhythmias. In pursuit of elucidating the causal link between the biological functions of mitochondria and the occurrence of atrial fibrillation/flutter, we conducted a 2-sample Mendelian randomization (MR) study. Mitochondrial proteins were selected for exposure in this study. To enhance the accuracy of our study, we selected data on AF/AFL from the FinnGen study and the UK Biobank for MR analysis, respectively. The inverse variance-weighted method was utilized as the primary analysis technique for MR. In addition, we performed a series of sensitivity analyses to detect heterogeneity and horizontal pleiotropy. MR results indicated a significant positive association between NAD-dependent protein deacylase sirtuin-5 and AF/AFL (odds ratio = 1.084, 95% confidence interval: 1.037-1.133, P = 3.679 × 10-4, Adjusted P = .024), with consistent outcomes observed in replication analysis (odds ratio = 1.002, 95% confidence interval: 1.001-1.003, P = 4.808 × 10-4, Adjusted P = .032). NAD-dependent protein deacylase sirtuin-5 can significantly promote the occurrence of AF/AFL, and its specific mechanisms warrant further investigation.

Effectiveness and safety of dolutegravir plus lamivudine in treating HIV in China, including outcomes of patients coinfected with tuberculosis.

Antiretroviral regimens for human immunodeficiency virus (HIV) infection have continuously evolved; however, antiretrovirals can cause severe adverse reactions. Two-drug regimen therapy can decrease lifetime cumulative drug exposure and long-term toxicities associated with multiple antiretrovirals. The preferred 2-drug regimen constitutes dolutegravir (DTG) and lamivudine (3TC). This study determined the rate of virological suppression and incidence of adverse events at week 48 in treatment-naïve people living with HIV initiated on DTG + 3TC. This was a single-center, retrospective, observational study. Treatment-naïve people aged ≥18 years who received at least 1 DTG + 3TC dose between May 2020 and May 2022 were included. Eighty-nine people living with HIV were enrolled. Twenty-five (28.1%) patients with a DTG + 3TC regimen at baseline were analyzed because of comorbidities, and 48% because of concomitant tuberculosis (TB). Viral suppression at 48 weeks was achieved in 91.67% of patients, and TB was well controlled. At week 48, 84 (94.38%) patients had viral loads < 50 copies/mL, and 21 (91.31%) of the 23 participants with a baseline HIV-1-RNA level ≥ 1 × 105 copies/mL achieved virological success. Fifteen (88.23%) of the 17 participants with a baseline CD4 + cell count of <200 cells/µL achieved virological suppression. The median CD4 + cell count change from baseline was 539.5 cells/µL. No significant changes in triglycerides, low-density lipoprotein cholesterol, weight, or creatinine were observed from baseline to 48 weeks. One patient had severe insomnia at 4 weeks. Our findings support the real-world effectiveness and low metabolic impact of DTG + 3TC. Using DTG + 3TC in patients coinfected with TB and HIV has favorable therapeutic outcomes.

Loosely Bounded Exciton with Enhanced Delocalization Capability Boosting Efficiency of Organic Solar Cells.

In organic solar cells (OSCs), electron acceptors have undergone multiple updates, from the initial fullerene derivatives, to the later acceptor-donor-acceptor type non-fullerene acceptors (NFAs), and now to Y-series NFAs, based on which efficiencies have reached over 19%. However, the key property responsible for further improved efficiency from molecular structure design is remained unclear. Herein, the material properties are comprehensively scanned by selecting PC71BM, IT-4F, and L8-BO as the representatives for different development stages of acceptors. For comparison, asymmetric acceptor of BTP-H5 with desired loosely bounded excitons is designed and synthesized. It's identified that the reduction of intrinsically exciton binding energy (Eb) and the enhancement of exciton delocalization capability act as the key roles in boosting the performance. Notably, 100 meV reduction in Eb has been observed from PC71BM to BTP-H5, correspondingly, electron-hole pair distance of BTP-H5 is almost two times over PC71BM. As a result, efficiency is improved from 40% of S-Q limit for PC71BM-based OSC to 60% for BTP-H5-based one, which achieves an efficiency of 19.07%, among the highest values for binary OSCs. This work reveals the confirmed function of exciton delocalization capability quantitatively in pushing the efficiency of OSCs, thus providing an enlightenment for future molecular design.

Cytology or Multiparameter Flow Cytometry Positivity in the Cerebrospinal Fluid Before Transplantation is Predictive of Poor Outcomes After Allotransplantation in Acute Myeloid Leukemia Patients.

INTRODUCTION: Central nervous system leukemia (CNSL) remains a serious complication in patients with acute myeloid leukemia (AML) and an ambiguous prognostic factor for those receiving allo-geneic hematopoiesis stem cell transplantation (allo-HSCT). It is unknown whether using more sensitive tools, such as multiparameter flow cytometry (MFC), to detect blasts in the cerebrospinal fluid (CSF) would have an impact on outcome. METHODS: We retrospectively analyzed the clinical outcomes of 1472 AML patients with or without cytology or MFC positivity in the CSF before transplantation. Abnormal CSF (CSF+) was detected via conventional cytology and MFC in 44 patients at any time after diagnosis. A control group of 175 CSF-normal (CSF-) patients was generated via propensity score matching (PSM) analyses according to sex, age at transplant, and white blood cell count at diagnosis. RESULTS: Compared to those in the CSF-negative group, the conventional cytology positive and MFC+ groups had comparable 8-year nonrelapse mortality (NRM) (4%, 4%, and 6%, p = 0.82), higher cumulative incidence of relapse (CIR) (14%, 31%, and 32%, p = 0.007), lower leukemia-free survival (LFS) (79%, 63%, and 64%, p = 0.024), and overall survival (OS) (83%, 63%, and 68%, p = 0.021), with no significant differences between the conventional cytology positive and MFC+ groups. Furthermore, multivariate analysis confirmed that CSF involvement was an independent factor affecting OS and LFS. CONCLUSION: Our results indicate that pretransplant CSF abnormalities are adverse factors independently affecting OS and LFS after allotransplantation in AML patients.

Lactylated Apolipoprotein C-II Induces Immunotherapy Resistance by Promoting Extracellular Lipolysis.

Mortality rates due to lung cancer are high worldwide. Although PD-1 and PD-L1 immune checkpoint inhibitors boost the survival of patients with non-small-cell lung cancer (NSCLC), resistance often arises. The Warburg Effect, which causes lactate build-up and potential lysine-lactylation (Kla), links immune dysfunction to tumor metabolism. The role of non-histone Kla in tumor immune microenvironment and immunotherapy remains to be clarified. Here, global lactylome profiling and metabolomic analyses of samples from patients with NSCLC is conducted. By combining multi-omics analysis with in vitro and in vivo validation, that intracellular lactate promotes extracellular lipolysis through lactyl-APOC2 is revealed. Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis. Moreover, the anti-APOC2K70-lac antibody that sensitized anti-PD-1 therapy in vivo is developed. This findings highlight the potential of anti lactyl-APOC2-K70 approach as a new combination therapy for sensitizing immunotherapeutic responses.

Patient-reported symptom burden and circulating cytokines undergoing chemotherapy: a pilot study in patients with ovarian cancer.

OBJECTIVE: To analyze the fluctuations of patient-reported outcomes (PROs) and their relationships with cytokines in the peripheral blood of patients undergoing chemotherapy for ovarian cancer (OC). METHODS: PROs burden was prospectively measured by the M.D. Anderson Symptom Inventory-Ovarian Cancer (MDASI-OC) at baseline before chemotherapy, on a daily basis during and post-chemotherapy days (PCD) 7, 14, and 20. Cytokines were collected at baseline, days prior to hospital discharge and PCD 20. Pearson correlation was used to explore the associations between PROs and cytokines levels in peripheral blood. RESULTS: The top 8 rated symptoms were compared between the neoadjuvant chemotherapy (NACT) group (n=20) and the postoperative adjuvant chemotherapy (PAC) group (n=7). Before chemotherapy, the mean scores of fatigue and lack of appetite in the NACT group were higher than those in the PAC group. After chemotherapy, pain, nausea, vomiting, disturbed sleep, lack of appetite, and constipation increased to peak during PCD 2-6; while, fatigue and numbness or tingling remained at high levels over PCD 2-13. By PCD 20, disturbed sleep and fatigue showed a significant increase in mean scores, particularly in the NACT group; while, other symptom scores decreased and returned to baseline levels. Additionally, the longitudinal fluctuations in pain, fatigue, and lack of appetite were positively associated with circulating levels of interleukin-6 and interferon gamma (p<0.05). CONCLUSION: MDASI-OC was feasible and adaptable for demonstrating the fluctuations of symptom burden throughout chemotherapy course. Moreover, symptoms changing along with cytokines levels could provide clues for exploring mechanism underlying biochemical etiology.

Quantitative assessment of colour fundus photography in hyperopia children based on artificial intelligence.

OBJECTIVES: This study aimed to quantitatively evaluate optic nerve head and retinal vascular parameters in children with hyperopia in relation to age and spherical equivalent refraction (SER) using artificial intelligence (AI)-based analysis of colour fundus photographs (CFP). METHODS AND ANALYSIS: This cross-sectional study included 324 children with hyperopia aged 3-12 years. Participants were divided into low hyperopia (SER+0.5 D to+2.0 D) and moderate-to-high hyperopia (SER≥+2.0 D) groups. Fundus parameters, such as optic disc area and mean vessel diameter, were automatically and quantitatively detected using AI. Significant variables (p<0.05) in the univariate analysis were included in a stepwise multiple linear regression. RESULTS: Overall, 324 children were included, 172 with low and 152 with moderate-to-high hyperopia. The median optic disc area and vessel diameter were 1.42 mm2 and 65.09 µm, respectively. Children with high hyperopia had larger superior neuroretinal rim (NRR) width and larger vessel diameter than those with low and moderate hyperopia. In the univariate analysis, axial length was significantly associated with smaller superior NRR width (ß=-3.030, p<0.001), smaller temporal NRR width (ß=-1.469, p=0.020) and smaller vessel diameter (ß=-0.076, p<0.001). A mild inverse correlation was observed between the optic disc area and vertical disc diameter with age. CONCLUSION: AI-based CFP analysis showed that children with high hyperopia had larger mean vessel diameter but smaller vertical cup-to-disc ratio than those with low hyperopia. This suggests that AI can provide quantitative data on fundus parameters in children with hyperopia.

Investigation of vascular risk factor control and secondary prevention medication compliance in acute ischemic stroke.

Objectives: This study aimed to investigate the management of vascular risk factors, with a specific focus on understanding the various factors affecting risk factor control through an in-depth analysis of clinical data and a longitudinal follow-up of patients who have experienced ischemic strokes. Methods: A total of 1,572 participants were included in the analysis. We assessed thresholds for blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), and glycated hemoglobin (HbA1c) levels to uncover the contextual conditions and factors affecting vascular risk factor control. Moreover, the study also scrutinized medication compliance at intervals of 3, 6, and 12 months post-onset. Logistic regression was used to adjust for confounding factors. Results: At 3, 6, and 12 months, BP,LDL, hemoglobin control targets were achieved in 50.7, 51.8, and 50.6%; 51.5, 59.4, and 50.6%; 48.1, 44.0, and 48.4%,respectively. Notably, age was associated with the achievement of BP control (odds ratio [OR], 0.96; 95% confidence intervals [CI], 0.94-0.98; p < 0.0001). Ethnic minorities (OR, 4.23; 95% CI, 1.19-15.09; p = 0.02) and individuals with coronary heart disease (OR, 0.5; 95% CI, 0.3-1.0; p = 0.05) experienced decreased BP control ratios. A previous history of stroke (OR, 1.7; 95% CI, 1.0-2.8; p = 0.03) and unrestricted alcohol consumption (OR, 3.3; 95% CI, 1.0-11.1; p = 0.05) was significantly associated with the achievement of lipid control. Furthermore, lifestyle modifications were significantly correlated with the achievement of BP control (OR, 0.19; 95% CI, 0.12-0.30; p < 0.01), blood glucose control (OR, 0.03; 95% CI, 0.01-0.08; p < 0.01), and blood lipid control (OR, 0.26; 95% CI, 0.16-0.42; p < 0.01). The absence of regular physical activity was associated with lower rates of glycemic (OR, 0.14; 95% CI, 0.06-0.36; p < 0.01) and lipid controls (OR, 0.55; 95% CI, 0.33-0.90; p = 0.01). Over time, overall medication compliance declined. Conclusion: Within the cohort of patients under medication, the compliance rate concerning vascular risk factors remains unsatisfactory. Attention should be paid to compliance with secondary prevention medications and enhance the control of vascular risk factors, as compliance emerges as the key to effective prevention.

Clinical biomarker-based biological aging and risk of benign prostatic hyperplasia: A large prospective cohort study.

Objective: Chronological age (CAge), biological age (BAge), and accelerated age (AAge) are all important for aging-related diseases. CAge is a known risk factor for benign prostatic hyperplasia (BPH); However, the evidence of association of BAge and AAge with BPH is limited. This study aimed to evaluate the association of CAge, Bage, and AAge with BPH in a large prospective cohort. Method: A total of 135,933 males without BPH at enrolment were extracted from the UK biobank. We calculated three BAge measures (Klemera-Doubal method, KDM; PhenoAge; homeostatic dysregulation, HD) based on 16 biomarkers. Additionally, we calculated KDM-BAge and PhenoAge-BAge measures based on the Levine method. The KDM-AAge and PhenoAge-AAge were assessed by the difference between CAge and BAge and were standardized (mean = 0 and standard deviation [SD] = 1). Cox proportional hazard models were applied to assess the associations of CAge, Bage, and AAge with incident BPH risk. Results: During a median follow-up of 13.150 years, 11,811 (8.690%) incident BPH were identified. Advanced CAge and BAge measures were associated with an increased risk of BPH, showing threshold effects at a later age (all P for nonlinearity <0.001). Nonlinear relationships between AAge measures and risk of BPH were also found for KDM-AAge (P = 0.041) and PhenoAge-AAge (P = 0.020). Compared to the balance comparison group (-1 SD < AAge < 1 SD), the accelerated aging group (AAge > 2 SD) had a significantly elevated BPH risk with hazard ratio (HR) of 1.115 (95% CI, 1.000-1.223) for KDM-AAge and 1.180 (95% CI, 1.068-1.303) for PhenoAge-AAge, respectively. For PhenoAge-AAge, subgroup analysis of the accelerated aging group showed an increased HR of 1.904 (95% CI, 1.374-2.639) in males with CAge <50 years and 1.233 (95% CI, 1.088-1.397) in those having testosterone levels <12 nmol/L. Moreover, AAge-associated risk of BPH was independent of and additive to genetic risk. Conclusions: Biological aging is an independent and modifiable risk factor for BPH. We suggest performing active health interventions to slow biological aging, which will help mitigate the progression of prostate aging and further reduce the burden of BPH.

Value of endoscopic grading of gastroesophageal flap valve in gastroesophageal reflux disease.

OBJECTIVE: To investigate the significance of endoscopic grading (Hill's classification) of gastroesophageal flap valve (GEFV) in the examination of patients with gastroesophageal reflux disease (GERD). METHODS: One hundred and sixty-two patients undergoing gastroscopy in the Department of Gastroenterology, Xingyi People's Hospital between Apr. 2022 and Sept. 2022 were selected by convenient sampling, and data such as GEFV grade, and findings of esophageal high-resolution manometry (HRM) and esophageal 24-h pH/impedance reflux monitoring, and Los Angeles (LA) classification of reflux esophagitis (RE) were collected and compared. RESULTS: Statistically significant differences in age (F = 9.711, P < 0.001) and hiatal hernia (χ = 35.729, P < 0.001) were observed in patients with different GEFV grades. The resting LES pressures were 12.12 ± 2.79, 10.73 ± 2.68, 9.70 ± 2.29, and 8.20 ± 2.77 mmHg (F = 4.571, P < 0.001) and LES lengths were 3.30 ± 0.70, 3.16 ± 0.68, 2.35 ± 0.83, and 2.45 ± 0.62 (F = 3.789, P = 0.011), respectively, in patients with GEFV grades I-IV. DeMeester score (Z = 5.452, P < 0.001), AET4 (Z = 5.614, P < 0.001), acid reflux score (upright) (Z = 7.452, P < 0.001), weak acid reflux score (upright) (Z = 3.121, P = 0.038), liquid reflux score (upright) (Z = 3.321, P = 0.031), acid reflux score (supine) (Z = 6.462, P < 0.001), mixed reflux score (supine) (Z = 3.324, P = 0.031), gas reflux score (supine) (Z = 3.521, P = 0.024) were different in patients with different GEFV grades, with statistically significant differences. Pearson correlation analysis revealed a positive correlation between RE grade and LA classification of GERD (r = 0.662, P < 0.001), and the severity of RE increased gradually with the increase of the Hill grades of GEFV. CONCLUSION: The Hill grade of GEFV is related to age, hiatal hernia, LES pressure, and the consequent development and severity of acid reflux and RE. Evaluation of esophageal motility and reflux based on the Hill grade of GEFV is of significance for the diagnosis and treatment of GERD.

Development of a diagnostic nomogram for alpha-fetoprotein-negative hepatocellular carcinoma based on serological biomarkers.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Serum biomarkers play an important role in the early diagnosis and prognosis of HCC. Because a certain percentage of HCC patients are negative for alpha-fetoprotein (AFP), the diagnosis of AFP-negative HCC is essential to improve the detection rate of HCC. AIM: To establish an effective model for diagnosing AFP-negative HCC based on serum tumour biomarkers. METHODS: A total of 180 HCC patients were enrolled in this study. The expression levels of GP73, des-γ-carboxyprothrombin (DCP), CK18-M65, and CK18-M30 were detected by a fully automated chemiluminescence analyser. The variables were selected by logistic regression analysis. Several models were constructed using stepwise backward logistic regression. The performance of the models was compared using the C statistic, integrated discrimination improvement, net reclassification improvement, and calibration curves. The clinical utility of the nomogram was assessed using decision curve analysis (DCA). RESULTS: The results showed that the expression levels of GP73, DCP, CK18-M65, and CK18-M30 were significantly greater in AFP-negative HCC patients than in healthy controls (P < 0.001). Multivariate logistic regression analysis revealed that GP73, DCP, and CK18-M65 were independent factors for diagnosing AFP-negative HCC. By comparing the diagnostic performance of multiple models, we included GP73 and CK18-M65 as the model variables, and the model had good discrimination ability (area under the curve = 0.946) and good goodness of fit. The DCA curves indicated the good clinical utility of the nomogram. CONCLUSION: Our study identified GP73 and CK18-M65 as serum biomarkers with certain application value in the diagnosis of AFP-negative HCC. The diagnostic nomogram based on CK18-M65 combined with GP73 demonstrated good performance and effectively identified high-risk groups of patients with HCC.

[Design and application of a disposable self-destructed and sheath-encased sterile acupuncture needle].

A kind of disposable self-destructed and sheath-encased sterile acupuncture needle is designed to efficiently solve the issues of safety and sterilization encountered in the routine operation of acupuncture. The needle consists of three components, i.e. the needle body, the sheath and the locker. The needle body is movable and rotatable in the sheath, but can not be separated from the sheath. It is convenient for the operator to perform the lifting-thrusting and twisting techniques, and to prevent the non-punctured portion of the body from being out off the sheath so that a sterile confined room is formed between the needle and the skin of the operated area. With a locker installed between the sheath and the needle handle, after needle removal, the needle body can be returned and locked in the sheath, avoiding the exposure of needle tip, obtaining the self-destruction of needle and preventing from needling accident and reuse of needle. The devise is operated easily, which is effectively reduce the risk of infection and ensure the safety of medical staffs in practice.