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*

Recent clinical trials have demonstrated a protective effect in using traditional Chinese medicine Tongxinluo (TXL) capsule to treat atherosclerosis. However, clinical evidence of the effects of TXL treatment on coronary plaque vulnerability is unavailable. In response, we developed this study to investigate the hypothesis that on the basis of statin therapy, treatment with TXL capsule may stabilize coronary lesions in patients with acute coronary syndrome (ACS). The TXL-CAP study was an investigator-initiated, randomized, double-blind clinical trial conducted across 18 medical centers in China. Patients with ACS aging from 18 to 80 years old who had a non-intervened coronary target lesion with a fibrous cap thickness (FCT) < 100 μm and lipid arc > 90° as defined by optical coherence tomography (OCT) were recruited. A total of 220 patients who met the selection criteria but did not meet the exclusion criteria will be finally recruited and randomized to receive treatment with TXL (n = 110) or placebo (n = 110) for a duration of 12 months. The primary endpoint was the difference in the minimum FCT of the coronary target lesion between TXL and placebo groups at the end of the 12-month follow-up. Secondary endpoints included: (1) changes of the maximum lipid arc and length of the target plaque, and the percentage of lipid, fibrous, and calcified plaques at the end of the 12-month period; (2) the incidence of composite cardiovascular events and coronary revascularization within the 12 months; (3) changes in the grade and scores of the angina pectoris as assessed using the Canadian Cardiovascular Society (CCS) grading system and Seattle angina questionnaire (SAQ) score, respectively; and (4) changes in hs-CRP serum levels. The results of the TXL-CAP trial will provide additional clinical data for revealing whether TXL capsules stabilizes coronary vulnerable plaques in Chinese ACS patients.

Objective:To investigate the differences in clinical outcomes of septic children with varying serum zinc levels,and to analyze the relationship between reduced serum zinc levels and organ dysfunction as well as 28-day mortality in septic children.Methods:This study conducted a retrospective analysis of clinical data from pediatric patients diagnosed with sepsis or septic shock in the Department of critical care medicine of the children's Hospital of Soochow University between January 2017 and December 2022.Clinical characteristics,organ dysfunction,and prognosis were compared between two groups:children with low serum zinc levels and those with normal zinc levels.Results:The serum zinc level of septic children within 24 hours of admission was 9.60(5.52,13.80)μmol/L,with 50.54%(94/186)of the children exhibiting low serum zinc levels(<10.07 μmol/L).Compared to the normal serum zinc group,the low serum zinc group had a significantly lower Pediatric Critical Illness Score(PCIS)[(78.71±9.35)vs.(85.12±8.51),P=0.005]and higher 28-day mortality(46.80%vs.14.13%,P<0.001).The low serum zinc group also had a higher proportion of invasive mechanical ventilation(64.89%vs.47.82%,P=0.019),renal replacement therapy(15.59%vs.3.26%,P=0.003),and use of vasoactive drugs(56.38%vs.30.43%,P<0.001).The rate of underlying conditions in the low serum zinc group was significantly higher than that in the normal serum zinc group(57.44%vs.36.95%,P=0.005).Additionally,the low serum zinc group had a higher incidence of disseminated intravascular coagulation(DIC),respiratory failure,acute kidney injury,shock,and multiple organ dysfunction syndrome(MODS)compared to the normal serum zinc group(P<0.05).Serum zinc levels had predictive value for 28-day mortality in septic children(AUC=0.813;95%CI:0.725～0.902;P<0.001).A serum zinc level of less than 6.950 μmol/L predicted the death of septic children with a sensitivity of 0.618 and a specificity of 0.902.Conclusion:Sepsis in children is commonly associated with low serum zinc levels,especially in those with underlying conditions such as hematologic and oncologic disorders.Sepsis patients hypozincemia with a higher incidence of DIC,respiratory failure,acute kidney injury,shock,and MODS.A serum zinc level below 6.95 μmol/L serves as a significant predictor of 28-day mortality in children with severe sepsis.

OpenSim is an open source, free motion simulation and gait analysis software, which can be used to dynamically simulate and analyze the complex motion of the human body, and is widely used in human biomechanical research. Since OpenSim can analyze multi-dimensional motion data such as muscle strength, joint torque, and muscle synergistic activation during human movement, it can be used to study the biomechanical mechanism of musculoskeletal imbalance diseases and various treatment methods in TCM orthopedics, and has a broad application prospect in the field of TCM orthopedics. By the analysis of the basic characteristics, elements, analysis process, and application prospects of OpenSim, it is concluded that OpenSim musculoskeletal model has a large application space in the field of traditional Chinese medicine orthopedic, which is helpful to explain the pathogenesis and mechanism of diseases, and promote the precision diagnosis and treatment of orthopedics diseases;the application of OpenSim musculoskeletal model can solve the problem that the previous research paid attention to the bone malalignment and not enough attention to the tendon, and provide a new method for the research of orthopedic diseases. At present, there are still problems in the promotion and application of OpenSim, such as large equipment requirements and high operation threshold. Therefore, multidisciplinary cooperation, clinical research, and data sharing are the basic research strategies in this field.
Humans ; Biomechanical Phenomena ; Orthopedics ; Traumatology ; Software ; Medicine, Chinese Traditional ; Musculoskeletal System ; Models, Biological

Objective:To investigate the effect of miR-1-3p on mitophagy in human esophageal squamous cell carcinoma (ESCC) cells and the related mechanisms.Methods:The differentially expressed miRNAs in ESCC were screened using the GEO database. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure miR-1-3p expression in normal esophageal epithelial cells (HET-1A) and ESCC cell lines (TE1, KYSE30, KYSE150, KYSE410, Eca109). Bioinformatics tools were utilized to predict target genes of miR-1-3p, subcellular localization was confirmed by fluorescence in situ hybridization. The targeting relationship between miR-1-3p and SLC7A11 was validated using dual-luciferase reporter assay. Cell proliferation and apoptosis were detected by CCK8 assay and flow cytometry, respectively. Furthermore, experimental validation demonstrated that overexpression of SLC7A11 rescued the presence of the miR-1-3p/SLC7A11 axis. Confocal microscopy was used to detect changes in mitochondrial autophagic lysosomes, while transmission electron microscopy was employed to observe mitophagy and morphological alterations. Western blot was conducted to evaluate the expression of autophagy-related proteins LC3 and P62. Flow cytometry was used to measure mitochondrial membrane potential and reactive oxygen species (ROS). Immunohistochemistry was applied to assess SLC7A11 expression in 133 ESCC patient tissues and 115 normal esophageal epithelial tissues. The correlation between SLC7A11 expression level and clinicopathological features was analyzed. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard regression models were used for multivariate analysis.Results:The expression of miR-1-3p in ESCC cells was significantly lower than that in HET-1A cells ( P＜0.05). SLC7A11 was a target gene of miR-1-3p. Transfection of miR-1-3p mimic inhibited the proliferation of ESCC cells. CCK-8 assay results showed that the proliferative capacity of KYSE30 and KYSE410 cells in the miR-1-3p mimic group (absorbance values: 2.88±0.24 and 2.88±0.18, respectively) was significantly lower than that in the miRNA mimic negative control (NC) group (3.94±0.27, P＜0.001; 4.20±0.21, P＜0.001). Meanwhile, the proliferative capacity of KYSE30 and KYSE410 cells in the miR-1-3p mimic+SLC7A11-overexpression (OE) group (absorbance values: 3.57±0.15 and 3.60±0.13, respectively) was significantly higher than that in the miR-1-3p mimic +empty vector (EV) group (2.54±0.10, P＜0.001, 2.36±0.16, P＜0.001). Additionally, transfection of miR-1-3p mimic promoted apoptosis. Flow cytometry results demonstrated that the apoptosis rates of KYSE30 and KYSE410 cells in the miR-1-3p mimic group [(9.22±0.05)% and (6.55±0.37)%, respectively] were significantly higher than those in the miRNA mimic NC group [(0.81±0.17)%, P＜0.001); (1.04±0.12)%, P＜0.001]. Conversely, the apoptosis rates of KYSE30 and KYSE410 cells in the miR-1-3p mimic + SLC7A11-OE group [(0.73±0.04)% and (1.19±0.05)%, respectively] were significantly lower than those in the miR-1-3p mimic+EV group [(9.83±0.41)%, P＜0.001); (6.09±0.17)%, P＜0.00)]. MiR-1-3p mimic downregulated SLC7A11 protein expression and the LC3Ⅱ/LC3I ratio ( P＜0.05), upregulated P62 protein expression ( P＜0.05), this phenomenon can be rescued by overexpressing SLC7A11 ( P＜0.05). Additionally, miR-1-3p mimic increased ROS levels and decreased mitochondrial membrane potential (JC-1 aggregate/monomer ratio), this phenomenon can be rescued by overexpressing SLC7A11 ( P＜0.05). SLC7A11 expression was higher in ESCC tissues compared to normal esophageal epithelial tissues ( P＜0.001), and SLC7A11 serves as an independent prognostic factor in ESCC ( HR=2.15, 95% CI: 1.27-3.65, P=0.004). Conclusion:miR-1-3p inhibits mitophagy in esophageal squamous cell carcinoma by targeting SLC7A11.

Objective To verify the efficacy of a domestic human DNA quantification kit based on real-time fluorescence quantitative PCR in detecting the total human DNA concentration,male DNA concen-tration in mixed male/female DNA samples,the degree of DNA degradation and inhibitor tolerance.Methods Samples with different concentrations,different male/female ratios,different concentrations of inhibitors,and different degradation degrees were tested using the domestic human DNA quantification kit based on real-time fluorescence quantitative PCR.This kit was compared with a similar product on the market and was applied to the detection of DNA from real cases.Results This human DNA quan-tification kit can effectively detect human DNA as low as 0.001 65 ng/μL,and 6.25 pg/μL of male DNA in mixed samples with a male-to-female ratio of 1∶15 000.Even when the sample contains as high as 400 ng/μL of humic acid or 1 000 μmol/L of hemin alone,the DNA concentration can still be accurately detected.The degradation index can effectively characterize the degradation degree of the sample.This kit has been successfully applied in forensic practice.Conclusion This human DNA quan-tification kit is accurate and reliable in detection.It can accurately reflect the degradation of DNA and inhibitor tolerance.It has good performance in quantitative accuracy,determination of the male/female ratio in mixed samples,and inhibitor tolerance.It has application potential in forensic case examination.

Objective To establish a rapid screening and analysis method for etomidate and its ana-logues using a portable mass spectrometer equipped with a thermal desorption-atmospheric pressure chemical ionization source-linear ion trap.Methods A 10 μL aliquot of a standard solution at a con-centration of 1 μg/mL was taken,and after the solvent evaporated,the sample was inserted into the in-let of the portable mass spectrometer for detection.By adjusting the collision-induced dissociation pa-rameters,the molecular ion peak and fragment ion peak information of the standard were obtained and used to establish a reference database.In addition,the method was applied to 29 seized liquid and plant samples.Results A screening system for etomidate and its analogues was established based on the portable mass spectrometer and the corresponding mass spectrometry library.The system enables qualitative screening analysis by identifying primary protonated molecular ions and secondary product ions of etomidate and its analogues.The limits of detection for etomidate and its 12 analogues ranged from 0.1 to 10 μg/mL.Etomidate and its analogues were detected in all 29 liquid and plant samples.However,this method could not distinguish between isomeric imidazole esters,such as isopropoxate and propoxate.Additionally,when testing 2-SH-etomidate,there was a false positive for the detection of etomidate.Conclusion This study established a rapid screening method for etomidate and its ana-logues using a portable mass spectrometer.The method combines the high sensitivity of mass spectrome-try with the on-site applicability of portable devices,significantly improving detection efficiency and meeting the on-site detection needs of etomidate and its analogues.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.