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*

BACKGROUND: Our understanding of the correlation between postdischarge cancer and mortality in patients with coronary artery disease (CAD) remains incomplete. The aim of this study was to investigate the relationships between postdischarge cancers and all-cause mortality and cardiovascular mortality in CAD patients. METHODS: In this retrospective cohort study, 25% of CAD patients without prior cancer history who underwent coronary artery angiography between January 1, 2011 and December 31, 2015, were randomly enrolled using SPSS 26.0. Patients were monitored for the incidence of postdischarge cancer, which was defined as cancer diagnosed after the index hospitalization, survival status and cause of death. Cox regression analysis was used to explore the association between postdischarge cancer and all-cause mortality and cardiovascular mortality in CAD patients. RESULTS: A total of 4085 patients were included in the final analysis. During a median follow-up period of 8 years, 174 patients (4.3%) developed postdischarge cancer, and 343 patients (8.4%) died. A total of 173 patients died from cardiovascular diseases. Postdischarge cancer was associated with increased all-cause mortality risk (HR = 2.653, 95% CI: 1.727-4.076, P < 0.001) and cardiovascular mortality risk (HR = 2.756, 95% CI: 1.470-5.167, P = 0.002). Postdischarge lung cancer (HR = 5.497, 95% CI: 2.922-10.343, P < 0.001) and gastrointestinal cancer (HR = 1.984, 95% CI: 1.049-3.750, P = 0.035) were associated with all-cause mortality in CAD patients. Postdischarge lung cancer was significantly associated with cardiovascular death in CAD patients (HR = 4.979, 95% CI: 2.114-11.728, P < 0.001), and cardiovascular death was not significantly correlated with gastrointestinal cancer or other types of cancer. CONCLUSIONS Postdischarge cancer was associated with all-cause mortality and cardiovascular mortality in CAD patients. Compared with other cancers, postdischarge lung cancer had a more significant effect on all-cause mortality and cardiovascular mortality in CAD patients.

Objective To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS).Methods The pretreatment conditions of solid phase extraction(SPE)were op-timized by orthogonal experimental design and the surface water samples were concentrated and ex-tracted by Oasis? HLB and Oasis? MCX SPE columns in series.The extracts were separated by Kine-tex? EVO C18 column,with gradient elution of 0.1%formic acid aqueous solution and 0.1%formic acid methanol solution.Q-TOF-MS'fullscan'and'targeted MS/MS'modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion,prod-uct ion and retention times.Results The 34 emerging contaminants exhibited good linearity in the con-centration range respectively and the correlation coefficients(r)were higher than 0.97.The limit of de-tection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%.The intra-day precision was 0.78%-18.70%.The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected,with a concentration range of 1.93-157.71 ng/L.Conclusion The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.

Aim To observe the effects of Wenfei Jiangzhuo formula(WFJZF)on rats with vascular de-mentia and investigate its possible mechanism of ac-tion.Methods Thirty-six healthy male SD rats were randomly divided into the sham group,model group,donepezil group,and low-dose,medium-dose and high-dose groups of Wenfei Jiangzhuo formula,with six rats per group.Except for the sham group,the other groups were prepared as VaD models,and each group was gavaged with the corresponding drugs after suc-cessful modeling,and tests were performed after three weeks of treatment.Behavioral,hippocampal CA1 area morphology,neural dendrites and mitochondrial chan-ges were observed in all groups of rats,and phospho-glycerate mutase 5(PGAM5),dynamics-related pro-teins1(Drp1),opticatrophyprotein-1(OPA1),and other proteins were detected in each group.Results Compared with the sham group,rats in the model group and each intervention group had prolonged es-cape latency(P＜0.05),a shorter number of travers-als across the platforms(P＜0.05),a sparse morphol-ogy of hippocampal neurons,a reduction in the number of secondary dendritic spines,and a rupture of the out-er membrane of the mitochondria;the expression of the PGAM5 and Drp1 proteins in hippocampal tissues was elevated(P＜0.05),and the expression of the OPA1 and Mfn1/2 protein expression decreased(P＜0.05);compared with the model group,donepezil group and Wenfei Jiangzhuo formula high-dose group of rats had shorter evasion latency(P＜0.05),increased number of times to traverse the platform(P＜0.05),increased number of hippocampal neurons,tightly packed,more secondary dendritic structures,and reduced mitochon-drial damage;the expression of PGAM5 and Drp1 pro-teins was reduced(P＜0.05),and the expression of OPA1 and Mfn1/2 proteins was elevated(P＜0.05).Conclusions Wenfei Jiangzhuo formula can regulate the PGAM5-Drp1 signaling axis to improve the balance of mitochondrial homeostasis,thus improving the cog-nitive condition of the brain and exerting cerebroprotec-tive effects.

AIM:To investigate the effects and underlying mechanism of Toona sinensis bark extract(TAE)on the colon mucosal barrier and gut microbiota in mice with ulcerative colitis(UC)induced by dextran sulfate sodium(DSS).METHODS:Sixty C57BL/6J mice were randomly assigned to control,model,and mesalazine(0.2 g/kg)groups,as well as TAE groups(low,medium,and high-doses equal to crude drug concentrations of 2.3,4.6 and 9.2 g/kg,respectively).The UC model was induced by drinking of 2.5％DSS,and mean while the drugs were administered for 10 days.The mice were then evaluated in terms of weight,disease activity index(DAI),colon length,spleen index,and pathological changes in the colon tissues.In addition,the level of apoptosis in colon tissues was assessed by terminal de-oxynucleotidyl transferase dUTP nick-end labeling(TUNEL)fluorescence staining,and the expression of related proteins was evaluated by Western blot,levels of inflammatory factors were determined by enzyme-linked immunosorbent assays(ELISA),and the activities of total superoxide dismutase(T-SOD)and catalase(CAT)and malondialdehyde(MDA)content were assessed by biochemical assays.Furthermore,the constitution and diversity of the gut microbiota were inves-tigated by 16S rRNA gene sequencing.RESULTS:Compared with the control group,mice in the model group showed significantly reduced body weights(P<0.01),and the colon length was shortened significantly(P<0.05).Marked in-creases in the DAI and spleen index were observed(P<0.01),along with severe damage to the colon mucosa(P<0.01).Mechanistically,the level of intestinal epithelial cell apoptosis was significantly raised(P<0.01).The model group showed markedly reduced expression of occludin and claudin-1(P<0.01),the level of IL-10,and activities of T-SOD and CAT in the colon tissues(P<0.01).While the levels of IL-6,IL-1β,TNF-α,and the MDA content were increased signif-icantly(P<0.05).The abundance and diversity of the gut microbiota were decreased in the model group(P<0.05).Com-pared with the model group,all these indicators were ameliorated by the administration of TAE(P<0.05).The abundance of pathogenic bacteria,including Proteobacteria and Escherichia-Shigella,was decreased remarkably(P<0.05),while that of probiotics,including Bacteroidota and Muribaculaceae,were increased significantly(P<0.05).The abundance and diversity of the gut microbiota were increased.CONCLUSION:Taken together,Toona sinensis bark alcohol extract can alleviate damage to the intestinal mucosa by suppressing the apoptosis of intestinal epithelial cell,reducing the inflam-matory response,and mitigating oxidative stress.Treatment with TAE could also maintain the homeostasis of the gut micro-biota by regulating the abundance,ultimately meliorate the function of intestinal mucosal barrier.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

This study was aimed at creating an engineered strain of Bacillus subtilis for efficient expression of biologically active type 2 toxin B(TcdB2)derived from a highly virulent strain of Clostridium difficile.The TcdB2 gene was cloned from ST1/RT027 strain genome DNA,incorporated into the PHT01 vector,and then transformed into B.subtilis strain WB800N for prokaryotic expression.Cell toxicity assays revealed that the recombinant TcdB2 exhibited cytotoxic effects in various cells.The engineered B.subtilis strain effectively expressed biologically active TcdB2,thus providing a basis for further exploration of the pathogenic mechanisms of highly virulent strains of C.difficile and establishing a foundation for potential vaccine can-didate targets.

Wnt/β-catenin is a signaling pathway associated with embryonic development, organ formation, cancer, and fibrosis. Its activation can repair kidney damage during acute kidney injury (AKI) and accelerate the occurrence of renal fibrosis after chronic kidney disease (CKD). Interestingly, p53 has also been found as a key modulator in AKI and CKD in recent years. Meantime, some studies have found crosstalk between Wnt/β-catenin signaling pathways and p53, but more evidence is required on whether they have synergistic effects in renal disease progression. This article reviews the role and therapeutic targets of Wnt/β-catenin and p53 in AKI and CKD and proposes for the first time that Wnt/β-catenin and p53 have a synergistic effect in the treatment of renal injury.

Wnt/β-catenin is a signaling pathway associated with embryonic development, organ formation, cancer, and fibrosis. Its activation can repair kidney damage during acute kidney injury (AKI) and accelerate the occurrence of renal fibrosis after chronic kidney disease (CKD). Interestingly, p53 has also been found as a key modulator in AKI and CKD in recent years. Meantime, some studies have found crosstalk between Wnt/β-catenin signaling pathways and p53, but more evidence is required on whether they have synergistic effects in renal disease progression. This article reviews the role and therapeutic targets of Wnt/β-catenin and p53 in AKI and CKD and proposes for the first time that Wnt/β-catenin and p53 have a synergistic effect in the treatment of renal injury.

Wnt/β-catenin is a signaling pathway associated with embryonic development, organ formation, cancer, and fibrosis. Its activation can repair kidney damage during acute kidney injury (AKI) and accelerate the occurrence of renal fibrosis after chronic kidney disease (CKD). Interestingly, p53 has also been found as a key modulator in AKI and CKD in recent years. Meantime, some studies have found crosstalk between Wnt/β-catenin signaling pathways and p53, but more evidence is required on whether they have synergistic effects in renal disease progression. This article reviews the role and therapeutic targets of Wnt/β-catenin and p53 in AKI and CKD and proposes for the first time that Wnt/β-catenin and p53 have a synergistic effect in the treatment of renal injury.