Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans ; Male ; Azoospermia/diagnostic imaging* ; Deep Learning ; Testis/pathology* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Sperm Retrieval ; Sertoli Cell-Only Syndrome/diagnostic imaging*

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Oligodendrocyte lineage cells, including oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), are essential in establishing and maintaining brain circuits. Autophagy is a conserved process that keeps the quality of organelles and proteostasis. The role of autophagy in oligodendrocyte lineage cells remains unclear. The present study shows that autophagy is required to maintain the number of OPCs/OLs and myelin integrity during brain aging. Inactivation of autophagy in oligodendrocyte lineage cells increases the number of OPCs/OLs in the developing brain while exaggerating the loss of OPCs/OLs with brain aging. Inactivation of autophagy in oligodendrocyte lineage cells impairs the turnover of myelin basic protein (MBP). It causes MBP to accumulate in the cytoplasm as multimeric aggregates and fails to be incorporated into integral myelin, which is associated with attenuated endocytic recycling. Inactivation of autophagy in oligodendrocyte lineage cells impairs myelin integrity and causes demyelination. Thus, this study shows autophagy is required to maintain myelin quality during aging by controlling the turnover of myelin components.
Animals ; Autophagy/physiology* ; Oligodendroglia/metabolism* ; Myelin Sheath/physiology* ; Aging/pathology* ; Myelin Basic Protein/metabolism* ; Cell Lineage/physiology* ; Mice ; Oligodendrocyte Precursor Cells ; Mice, Inbred C57BL ; Brain/cytology* ; Cells, Cultured ; Cell Count

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective To explore the mechanism of Xiakucao Xiaoliu Mixture against non-small cell lung cancer （NSCLC）. Methods The effective components of Xiakucao Xiaoliu Mixture were screened by TCMSP, BATMAN-TCM database and literature reviews. The targets of effective components were predicted. NSCLC related targets were collected by GeneCards, OMIM, PharmGKB, TTD and Drugbank, combined with the differential genes of Xiakucao Xiaoliu Mixture against Lewis lung cancer mice. The intersection targets of Xiakucao Xiaoliu Mixture against NSCLC were obtained. Cytoscape software was used to construct the network diagram of traditional Chinese medicine-active ingredients-core targets. STRING database was used to construct PPI network diagram. GO function enrichment analysis and KEGG pathway enrichment analysis of the intersection targets were performed by Metascape database to predict the key targets and active components of Xiakucao Xiaoliu Mixture against NSCLC, and Schrodinger software was used to perform molecular docking verification. Results The 32 active components and 24 intersection targets of Xiakucao Xiaoliu Mixture against NSCLC were obtained. 11 core targets such as ESR1, MAPK1 were found. The mechanism of action may be related to 30 signaling pathways such as cellular senescence, receptor activation, prolactin signaling pathway. Conclusion The active components of Xiakucao Xiaoliu Mixture act on multiple targets and signaling pathways to regulate complex biological processes. By regulating ESR1 agsinst NSCLC, it may play an important role in improving the survival rate and prognosis of female patients.

Objective:To explore the application of COVID-19-specific IgG antibody in identifying epidemic Omicron BA.5 strain infection.Method:Omicron BF.7/BA.5 naturally infected population, healthy population vaccinated with the COVID-19 vaccine, and Omicron BF.7/BA.5 breakthrough cases were enrolled into this study. The serum WT-S-IgG and BA.5-S-IgG were detected by indirect ELISA, and the serum-specific IgG antibody levels of different populations were compared. The application value of the two antibody titers and the ratio of the two antibodies in identifying Omicron BA.5 epidemic strain infection were explored by the ROC curve, aiming to provide technical support for pathogen diagnosis.Results:The antibody titers of WT-S-IgG and BA.5-S-IgG in the breakthrough cases were higher than those in the naturally infected population and the healthy population ( P<0.05). The area under the curve (AUC) of WT-S-IgG and BA.5-S-IgG in identifying epidemic Omicron BA.5 strain infection was 0.947 and 0.961, respectively. The AUC of BA.5-S-IgG and WT-S-IgG antibody titer ratio was 0.873. When the antibody titer ratio was 0.855, the sensitivity and specificity were 80.00% and 90.00%, respectively. According to the interval since the last infection, the AUC of the ratio of BA.5-S-IgG to WT-S-IgG antibody titer to identify the infection of epidemic strains less than 30 days and more than 30 days was 0.887 and 0.863, respectively, and the sensitivity and specificity were both above 80%. Conclusion:Both BA.5-S-IgG and WT-S-IgG, as well as the combination of these two antibodies, are of high value in the identification of epidemic strains.

Objective:To explore the application of COVID-19-specific IgG antibody in identifying epidemic Omicron BA.5 strain infection.Method:Omicron BF.7/BA.5 naturally infected population, healthy population vaccinated with the COVID-19 vaccine, and Omicron BF.7/BA.5 breakthrough cases were enrolled into this study. The serum WT-S-IgG and BA.5-S-IgG were detected by indirect ELISA, and the serum-specific IgG antibody levels of different populations were compared. The application value of the two antibody titers and the ratio of the two antibodies in identifying Omicron BA.5 epidemic strain infection were explored by the ROC curve, aiming to provide technical support for pathogen diagnosis.Results:The antibody titers of WT-S-IgG and BA.5-S-IgG in the breakthrough cases were higher than those in the naturally infected population and the healthy population ( P<0.05). The area under the curve (AUC) of WT-S-IgG and BA.5-S-IgG in identifying epidemic Omicron BA.5 strain infection was 0.947 and 0.961, respectively. The AUC of BA.5-S-IgG and WT-S-IgG antibody titer ratio was 0.873. When the antibody titer ratio was 0.855, the sensitivity and specificity were 80.00% and 90.00%, respectively. According to the interval since the last infection, the AUC of the ratio of BA.5-S-IgG to WT-S-IgG antibody titer to identify the infection of epidemic strains less than 30 days and more than 30 days was 0.887 and 0.863, respectively, and the sensitivity and specificity were both above 80%. Conclusion:Both BA.5-S-IgG and WT-S-IgG, as well as the combination of these two antibodies, are of high value in the identification of epidemic strains.

Rapid epidemiological screening for tuberculosis (TB) usually uses tuberculin pure protein derivative (PPD) skin test, which has limitations such as low specificity and high side effects. ESAT-6 and CFP-10 are secreted proteins of Mycobacterium tuberculosis, but the related genes are missing from Bacillus Calmette-Guerin (BCG). In this study, the fusion protein ESAT6-CFP10 (EC) was expressed and purified, and prepared into chitosan nanoparticles (EC-NPs), which were loaded into the microneedle patch and carried out the preliminary test of tuberculosis skin test. The drug loading capacity of MNP-EC-NPs (microneedle patch, MNP) can reach 0.03 μg per needle and 1.92 μg per patch. The shelf life of MNP-EC-NPs can reach 6 months at room temperature, and it can effectively penetrate the epidermis. Volunteer skin test results showed that MNP-EC-NPs can effectively distinguish between BCG vaccinators, and can effectively show positive reaction in the skin of tuberculosis patients without significant side effects. The experiment was approved by the Ethics Committee of Wuhan Pulmonary Hospital [2022 (2)]. In this study, a TB skin test method was established, using ESAT6-CFP10 fusion protein instead of PPD, and using soluble microneedle dosage form, which improved the specificity of TB skin test diagnosis and provided a new technical scheme for TB epidemic screening.

Objective To explore the molecular mechanism of Gualou Guizhi decoction which regulates the interferon regulator factor 5(IRF5)signaling pathway to inhibit M1 type microglia activation and reduce the inflammatory response to protect damaged nerve cells.Methods Microglia(BV2)cells were randomly divided into BV2-control,BV2-model,BV2-experimental-L,-M,-H groups.The BV2-control group was given routine culture;the BV2-model group used 100 ng·mL-1 lipopolysaccharide(LPS)to stimulate BV2 which establish an inflammatory model;the BV2-experimental-L,-M,-H groups were cultured in 50,100,200 μg·mL-1 GLGZD and 100 ng·mL-1 LPS.The HT22 cells were divided into the HT-22-blank group,HT-22-model group,HT-22-control group and HT-22 experimental group.HT-22-blank group were conventional culture;HT-22-model group were oxygen glucose deprivation was performed for 2 h,then the complete medium was replaced for 24 h;HT-22-control group were after 2 h of oxygen glucose deprivation,the 100 ng·mL-1 LPS conditioned medium was replaced and incubated for 24 h;HT-22-experimental group were after 2 h of oxygen glucose deprivation,the 200 μg·mL-1 GLGZD conditioned medium was added for 24 h.Interleukin-12(IL-12)and IL-23 were detected by enzyme-linked immunosorbent assay(ELISA);the protein of IRF5,cluster differentiation 16(CD1 6)and MHC class Ⅱ(MHC-Ⅱ)was detected by Western blot;the expression of the synaptic marker protein class Ⅲ β-Tubulin(Tuj-1)was observed by immunofluorescence.Results IL-12 contents in the BV2-control,BV2-model and BV2-experimental-L,-M,-H groups were(2.62±1.02),(10.67±3.22),(6.87±1.61),(3.96±1.22)and(3.36±1.04)pg·mL-1;IL-23 contents were(20.40±2.04),(77.08±3.25),(76.28±3.75),(63.96±4.94)and(54.48±3.34)pg·mL-1;relative expression levels of IRF5 protein were 0.80±0.41,2.22±0.69,1.11±0.11,0.92±0.39 and 0.65±0.29;relative expression levels of CD16 protein were 0.69±0.45,1.91±0.52,1.42±0.22,1.04±0.15 and 0.67±0.30;relative expression levels of MHC-Ⅱ protein were 0.89±0.27,1.96±0.19,1.34±0.38,1.15±0.19 and 0.68±0.24.BV2-experimental-M,-H groups were compared with the BV2-model group,the differences were statistically significant(all P＜0.05).The Tuj-1 protein expression levels were 28.85±6.69,14.44±1.98,7.75±1.12 and 20.05±3.54,determined in the HT22-blank,HT22-model,HT22-control and HT22-experimental groups.The HT22-experimental group was compared with the HT22-control group,the difference was statistically significant(P＜0.05).Conclusion GLGZD may reduces the activation of microglia M1 phenotype through IRF5 signaling pathway,and then inhibits inflammatory response to protect damaged nerve cells.