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*

The p21-activated kinase 4 (PAK4), a key regulator of malignancy, is negatively correlated with immune infiltration and has become an emergent drug target of cancer therapy. Given the lack of high efficacy PAK4 inhibitors, we herein reported the identification of a novel inhibitor 13 bearing a tetrahydrobenzofuro[2,3-c]pyridine tricyclic core and possessing high potency against MIA PaCa-2 and Pan02 cell lines with IC₅₀ values of 0.38 and 0.50 μmol/L, respectively. This compound directly binds to PAK4 in a non-ATP competitive manner. In the mouse Pan02 model, compound 13 exhibited significant tumor growth inhibition at a dose of 100 mg/kg, accompanied by reduced levels of PAK4 and its phosphorylation together with immune infiltration in mice tumor tissue. Overall, compound 13 is a novel allosteric PAK4 inhibitor with a unique tricyclic structural feature and high potency both in vitro and in vivo, thus making it worthy of further exploration.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

The global outbreak of monkeypox in 2022 has aroused widespread concern in public health. To date, the prevention and treatment of monkeypox has mainly relied on smallpox vaccines and drugs. This study aims to screen and obtain therapeutic antibodies with high affinity, neutralizing activity, and protective effects, and provide candidate molecules for the development of specific therapeutic antibodies against monkeypox. Therefore, humanized mice were immunized to screen for antibodies against the envelope protein of the mpox virus. Two M1R-specific antibodies, 12G5 and 12H6, were obtained, with the affinity of 0.095 nmol/L and 0.089 nmol/L, respectively. The 50% reduction of the plaque counts (PRNT₅₀) of 12G5 and 12H6 was (1.821±1.766) μg/mL and (17.605±2.383) μg/mL, respectively. The two antibodies targeted two binding epitopes of M1R. Moreover, 12H6 could protect 60% of mice from death following the vaccinia virus challenge. This study provides research materials for subsequent in-depth studies on the immunoprotection of mpox virus and potential therapeutic strategies.
Animals ; Mice ; Antibodies, Viral/immunology* ; Monkeypox virus/immunology* ; Mpox, Monkeypox/immunology* ; Antibodies, Neutralizing/immunology* ; Viral Envelope Proteins/immunology* ; Humans ; Antibodies, Monoclonal/biosynthesis* ; Female

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective:To explore the effects of dual task training assisted by a lower limb rehabilitation robot on lower extremity mobility and the walking ability of stroke survivors.Methods:Sixty-one stroke survivors were randomly divided into a control group and an experimental group with 30 in the control group and 31 in the experimental group. In addition to routine exercise training and physical therapy, both groups were given cognitive-motor dual task training 5 times a week for 3 weeks. But only in the experimental group was the dual task training assisted by a lower limb rehabilitation robot. Both groups′ lower limb motor function, walking ability, cognition, balance and ability in the activities of daily living were evaluated before and after the experiment using the Fugl-Meyer lower extremity assessment (FMA-LE), functional ambulation categories (FAC), the digital span test (DST), the Berg Balance Scale (BBS) and the Modified Barthel Index (MBI). Additionally, 6 survivors of a right hemisphere stroke from the experimental group received cognitive-motor dual task training both with and without the robotic assistance alternately. Near-infrared functional brain imaging was applied before and after the intervention, and the functional network connectivity of the resting brains was analyzed.Results:After the intervention the average FMA-LE, FAC, BBS and MBI scores had improved in both groups, with the improvement in the experimental group significantly better than in the control group on average. In terms of cognition there was no significant difference in the DST forward and backward assessment results between the two groups. The analysis of brain network functional connectivity showed that the intensity of functional connectivity between the left prefrontal cortex (PFC) and the left premotor cortex and supplementary motor cortex (PMC/SMA) increased significantly more, on average, after training assisted by the robot.Conclusion:Dual task training with the assistance of a lower limb rehabilitation robot can effectively improve the lower limb motor function, walking, balance and ability in the activities of daily living of stroke survivors. Enhanced functional connection of the PFC and the PMC/SMA in the healthy hemisphere induced by the robot may be the cause.

Objective This study aimed to investigate the lipid-lowering activity of LFBEP-C1 in high glucose-fed Caenorhabditis elegans(C.elegans). Methods In this study,the fermented barley protein LFBEP-C1 was prepared and tested for its potential anti-obesity effects on C.elegans.The worms were fed Escherichia coli OP50(E.coli OP50),glucose,and different concentrations of LFBEP-C1.Body size,lifespan,movement,triglyceride content,and gene expression were analyzed.The results were analyzed using ANOVA and Tukey's multiple comparison test. Results Compared with the model group,the head-swing frequency of C.elegans in the group of LFBEP-C1 at 20 μg/mL increased by 33.88%,and the body-bending frequency increased by 27.09%.This indicated that LFBEP-C1 improved the locomotive ability of C.elegans.The average lifespan of C.elegans reached 13.55 days,and the body length and width of the C.elegans decreased after LFBEP-C1 intake.Additionally,LFBEP-C1 reduced the content of lipid accumulation and triglyceride levels.The expression levels of sbp-1,daf-2,and mdt-15 significantly decreased,while those of daf-16,tph-1,mod-1,and ser-4 significantly increased after LFBEP-C1 intake.Changes in these genes explain the signaling pathways that regulate lipid metabolism. Conclusion LFBEP-C1 significantly reduced lipid deposition in C.elegans fed a high-glucose diet and alleviated the adverse effects of a high-glucose diet on the development,lifespan,and exercise behavior of C.elegans.In addition,LFBEP-C1 regulated lipid metabolism mainly by mediating the expression of genes in the sterol regulatory element-binding protein,insulin,and 5-hydroxytryptamine signaling pathways.

Objective To prepare decellularized scaffolds from rabbit cartilage at various concentrations and assess their physicochemical properties and compatibility with stem cells to provide an experimental basis for cartilage repair.Methods Bone marrow mesenchymal stem cells(BMSCs)were cultured using the Percoll density gradient separation method,and this was followed by flow cytometric analysis and testing of their osteogenic and chondrogenic differentiation capabilities.Cartilage pieces were excised from rabbit knees and hip joints and subjected to physical crushing,repeated freeze-thaw cycles,and mixed enzymatic digestion for decellularization.To compare and observe the physicochemical properties of the decellularized scaffolds at different concentrations,three groups of scaffolds(labelwd A,B,and C)were designed with concentrations of 100％,50％and 30％,with three replicates each.Third-generation PKH26-labeled BMSCs were seeded onto optimally concentrated scaffolds and cultured for 1 week to observe cell growth.Results Flow cytometry detected BMSC surface antigens with positive expression of CD44 and CD90 and negative expression of CD45.Osteogenic induction stained with alizarin red showed red calcific nodules,and chondrogenic induction stained with alcian blue showed blue cartilaginous nodules.No apparent cell morphology was observed in the three groups of scaffolds stained with hematoxylin-eosin,and toluidine blue.There was a significant difference in DNA concentration between decellularized samples and non-decellularized scaffolds(P＜0.05).The content of glycosaminoglycans was slightly lower than the normal values.Significant differences were observed between the three groups of scaffolds in terms of pore size,water absorption,porosity,tensile strength,and Young's modulus(P＜0.05).After co-cultivation of stem cells with the scaffolds,cell adhesion was found to be good.Conclusions Percoll density gradient separation can obtain high-purity rabbit BMSCs,and the mixed decellularization method is superior.Group B scaffolds were the most suitable for tissue-engineered cartilage repair.BMSCs cultured in vitro grew well on Group B scaffolds.

Aim To study the main active ingredients,key targets and pathways of Cigu Xiaozhi Decoction(CXD)based on network pharmacology,and to ana-lyze and verify the mechanism of CXD on the transfor-mation of"inflammatory cancer"in non-alcoholic steatohepatitis(NASH)by animal experiments.Meth-ods The potential targets and signaling pathways of CXD in the treatment of NASH"inflammatory carcino-ma"were predicted based on network pharmacology.The mouse model of NASH was induced by methionine-choline deficiency diet(MCD),and CXD and epider-mal growth factor receptor(EGFR)inhibitors were given for 28 days.The mice were killed after the inter-vention,and the liver histopathology of each group was observed by hematoxylin-eosin method(HE).The rel-ative expression levels of EGFR,phosphatidylinositol 3-kinase(PI3K)and protein kinase B(AKT)in liver tissue of mice in each group were detected by Western blot.The contents of interleukin-6(IL-6),interleu-kin-1 β(IL-1β)and tumor necrosis factor-α(TNF-α)in serum were detected by enzyme-linked immunosor-bent assay(ELISA).Results A total of 284 poten-tial active components,159 potential therapeutic tar-gets and 20 key targets of CXD were identified by net-work pharmacological screening.CXD could affect multiple biological processes such as cell proliferation and inflammatory response,involving multiple signa-ling pathways such as tumor and PI3K/AKT.Animal experiments showed that CXD could reduce the levels of IL-6,IL-1β and TNF-α in serum of NASH mice.The relative expression of PI3K and AKT protein in liv-er tissue decreased,and the relative expression of EG-FR protein was increased.Conclusion CXD can reg-ulate EGFR/PI3K/AKT signaling pathway by partici-pating in biological processes such as cell proliferation and inflammatory response,and improve liver tissue injury in NASH mice.