Male infertility has become a global concern, accounting for 20-70% of infertility. Dysfunctional spermatogenesis is the most common cause of male infertility; thus, treating abnormal spermatogenesis may improve male infertility and has attracted the attention of the medical community. Mitochondria are essential organelles that maintain cell homeostasis and normal physiological functions in various ways, such as mitochondrial oxidative phosphorylation (OXPHOS). Mitochondrial OXPHOS transmits electrons through the respiratory chain, synthesizes adenosine triphosphate (ATP), and produces reactive oxygen species (ROS). These mechanisms are vital for spermatogenesis, especially to maintain the normal function of testicular Sertoli cells and germ cells. The disruption of mitochondrial OXPHOS caused by external factors can result in inadequate cellular energy supply, oxidative stress, apoptosis, or ferroptosis, all inhibiting spermatogenesis and damaging the male reproductive system, leading to male infertility. This article summarizes the latest pathological mechanism of mitochondrial OXPHOS disorder in testicular Sertoli cells and germ cells, which disrupts spermatogenesis and results in male infertility. In addition, we also briefly outline the current treatment of spermatogenic malfunction caused by mitochondrial OXPHOS disorders. However, relevant treatments have not been fully elucidated. Therefore, targeting mitochondrial OXPHOS disorders in Sertoli cells and germ cells is a research direction worthy of attention. We believe this review will provide new and more accurate ideas for treating male infertility.
Male ; Humans ; Infertility, Male/metabolism* ; Oxidative Phosphorylation ; Mitochondria/metabolism* ; Spermatogenesis/physiology* ; Sertoli Cells/metabolism* ; Oxidative Stress/physiology* ; Animals ; Reactive Oxygen Species/metabolism*

Chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH) are both chronic progressive respiratory diseases that cannot be completely cured. COPD is characterized by irreversible airflow limitation, chronic airway inflammation, and gradual decline in lung function, whereas PH is characterized by pulmonary vasoconstriction, remodeling, and infiltration of inflammatory cells. These diseases have similar pathological features, such as vascular hyperplasia, arteriolar contraction, and inflammatory infiltration. Despite these well-documented observations, the exact mechanisms underlying the occurrence and development of COPD and PH remain unclear. Evidence that mitochondrial dynamics imbalance is one major factor in the development of COPD and PH. Mitochondrial dynamics is precisely regulated by mitochondrial fusion proteins and fission proteins. When mitochondrial dynamics equilibrium is disrupted, it causes mitochondrial and even cell morphological dysfunction. Mitochondrial dynamics participates in various pathological processes for heart and lung disease. Mitochondrial dynamics may be different in the early and late stages of COPD and PH. In the early stages of the disease, mitochondrial fusion increases, inhibiting fission, and thereby compensatorily increasing adenosine triphosphate (ATP) production. With the development of the disease, mitochondria decompensation causes excessive fission. Mitochondrial dynamics is involved in the development of COPD and PH in a spatiotemporal manner. Based on this understanding, treatment strategies for mitochondrial dynamics abnormalities may be different at different stages of COPD and PH disease. This article will provide new ideas for the potential treatment of related diseases.
Humans ; Mitochondrial Dynamics/physiology* ; Pulmonary Disease, Chronic Obstructive/metabolism* ; Hypertension, Pulmonary/metabolism* ; Mitochondria/metabolism* ; Animals

Objective:To explore the medication law of TCM compounds used in the treatment of non-small cell lung cancer (NSCLC).Methods:Clinical literature about TCM compounds in the treatment of NSCLC was retrieved from CNKI, Wanfang Data, PubMed and Web of Science core collection database from January 1st, 2003 to May 1st, 2023. The Python and the ancient and modern medical record cloud platform V2.3.7 were used to analyses frequency statistics and properties, and clustering analysis, factor analysis and association rule analysis were performed.Results:A total of 866 articles were included, with 660 effective TCM compounds, 647 kinds of Chinese materia medica. There were 36 kinds of high-frequency Chinese materia medica, such as Astragali Radix, Atractylodis Macrocephalae Rhizoma and Poria; the efficacy categories of Chinese materia medica mainly included tonics and phlegm resolving cough relieving and asthma relieving drugs. Cluster analysis obtained 4 clusters, factor analysis extracted 11 common factors, and association rule analysis obtained 37 highly supported combinations of Chinese materia medica. The most reliable triple drug combination among them was Astragali Radix-Atractylodis Macrocephalae Rhizoma-Hedyotis diffusa willd, and the double drug combination was Astragali Radix-Ligustri Lucidi Fructus.Conclusion:TCM for the treatment of NSCLC mainly focuses on strengthening the healthy qi, clearing heat, resolving phlegm and detoxifying toxins, supplemented by tonifying qi and activating blood circulation, dispelling dampness and resolving phlegm.

Objective To observe the value of deep learning(DL)models for automatic classification of echocardiographic views.Methods Totally 100 patients after heart transplantation were retrospectively enrolled and divided into training set,validation set and test set at a ratio of 7∶2∶1.ResNet18,ResNet34,Swin Transformer and Swin Transformer V2 models were established based on 2D apical two chamber view,2D apical three chamber view,2D apical four chamber view,2D subcostal view,parasternal long-axis view of left ventricle,short-axis view of great arteries,short-axis view of apex of left ventricle,short-axis view of papillary muscle of left ventricle,short-axis view of mitral valve of left ventricle,also 3D and CDFI views of echocardiography.The accuracy,precision,recall,F1 score and confusion matrix were used to evaluate the performance of each model for automatically classifying echocardiographic views.The interactive interface was designed based on Qt Designer software and deployed on the desktop.Results The performance of models for automatically classifying echocardiographic views in test set were all good,with relatively poor performance for 2D short-axis view of left ventricle and superior performance for 3D and CDFI views.Swin Transformer V2 was the optimal model for automatically classifying echocardiographic views,with high accuracy,precision,recall and F1 score was 92.56％,89.01％,89.97％and 89.31％,respectively,which also had the highest diagonal value in confusion matrix and showed the best classification effect on various views in t-SNE figure.Conclusion DL model had good performance for automatically classifying echocardiographic views,especially Swin Transformer V2 model had the best performance.Using interactive classification interface could improve the interpretability of prediction results to some extent.

Objective:To explore the characteristics, clinical manifestations and gene mutation types of Cornelia de Lange syndrome (CdLs), and to improve the understanding of the disease.Methods:Clinical data and gene test results of a pediatric case of CdLs diagnosed in the First Affiliated Hospital of Xinxiang Medical University in August 2019 were analyzed retrospectively.Results:A female patient with 2 years and 8 months old presented a special appearance with a low and flat nose, a wide eye distance, audition ears, a downward inclination of the mouth corner, a high arch of the jaw and a small jaw deformity, who had recurrent seizures, speech and mental retardation.The result of gene test showed the mutation of SMC1A gene c. 2923C > T, and thus the patient was diagnosed as type 2 CdLs. Conclusions:CdLs is a rare genetic metabolic disease with special facial features and physical signs.There is only one case of CdLs with gene mutation of SMC1A in China through literature review.The mutation of SMC1A gene c. 2923C>T in CdLs cases has not been reported at home and abroad, which expands the variation spectrum of the SMC1A gene.

A case of primary amoebic meningoencephalitis (PAM) treated in the First Affiliated Hospital of Xinxiang Medical University in March 6, 2022 was reported.The proband was a 14-year-old boy, who was admitted to the hospital because of " fever, headache and vomiting for 2 days" . Metagenomic next-generation sequencing (mNGS) was consequently conducted to examine the pathogens in cerebrospinal fluid.Naegleria infection was detected, so the child was diagnosed with PAM.The disease developed rapidly, and the patient died 29 hours after admission.In the paper, a total of 13 studies were reviewed, and 15 children with PAM were reported.Of the reported cases, only 1 case survived, 14 cases died.PAM had a low incidence, a dangerous condition, and high mortality.Most cases were diagnosed by autopsy or pathogen diagnosis in cerebrospinal fluid.This case is confirmed by mNGS of pathogens, and it is rarely reported at home and abroad.

Objective:To construct and verify the nomogram prediction model based on inflammatory indicators, underlying diseases, etiology and the British Thoracic Society modified pneumonia score (CURB-65 score) in adults with severe community acquired pneumonia (CAP).Methods:The clinical data of 172 adult inpatients first diagnosed as CAP at Taikang Xianlin Drum Tower Hospital from January 2018 to December 2021 were divided into severe and non-severe diseases groups according to the severity of their conditions. The baseline conditions (including gender, age, past history, comorbidities and family history), clinical data (including chief symptoms, onset time, CURB-65 score), first laboratory results on admission (including whole blood cell count, liver and kidney function, blood biochemistry, coagulation function, microbiological culture results) and whether the antimicrobial therapy was adjusted according to the microbiological culture results were recorded in both groups. Univariate analysis was used to screen for differential indicators between severe and non-severe patients. After covariate analysis, multi-factor Logistic regression analysis was performed based on the Aakaike information criterion (AIC) forward stepwise regression method to rigorously search for risk factors for constructing the model. Based on the results of the multi-factor analysis, a nomogram prediction model was constructed, and the discriminatory degree and calibration degree of the model were assessed using the receiver operator characteristic curve (ROC curve) and calibration curve.Results:A total of 172 adult CAP patients were included, 48 in severe group and 124 in non-severe group. The median age was 74 (57, 83) years old, onset time was 5.0 (3.0, 10.0) days, total number of comorbidities was 3 (2, 5), including 58 cases (33.7%) with hypertension and 17 (9.9%) with heart failure, 113 (65.7%) with CURB-65 score≤1, 34 cases (19.8%) had a CURB-65 score = 2 and 25 cases (14.5%) had a CURB-65 score≥3. Univariate analysis showed that there were statistically significant differences between the two groups in age, smoking history, CURB-65 score, heart rate, onset time, total comorbidity, pathogenic microorganisms, fibrinogen (FIB), D-dimer, C-reactive protein (CRP), procalcitonin (PCT), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Multi-factor Logistic regression analysis showed that hypertension [odds ratio ( OR) = 3.749, 95% confidence interval (95% CI) 1.411 to 9.962], heart failure ( OR = 4.616, 95% CI was 1.116 to 19.093), co-infection ( OR = 2.886, 95% CI was 1.073 to 7.760), history of smoking ( OR = 8.268, 95% CI was 2.314 to 29.537), moderate to high CURB-65 score ( OR = 4.833, 95% CI was 1.892 to 12.346), CRP ( OR = 1.012, 95% CI was 1.002 to 1.022), AST ( OR = 1.015, 95% CI was 1.001 to 1.030) were risk factors for severe CAP (all P < 0.05). The filtered indicators were included in the nomogram model, and the results showed that the area under the ROC curve (AUC) for the model to identify patients with severe adult CAP was 0.896, 95% CI was 0.840 to 0.937 ( P < 0.05), and the calibration curve showed that the predicted probability of severe CAP was in good agreement with the observed probability (Hosmer-Lemeshow test: χ2 = 6.088, P = 0.665). Conclusions:The nomogram model has a good ability to identify patients with severe adult CAP and can be used as a comprehensive and reliable clinical diagnostic tool to provide a evidence for timely intervention in the treatment of adults with severe CAP.

Objective:To analyze the functional connectivity (FC) characteristics of sensory motor network (SMN) in patients with bipolar disorder type Ⅰ (BD-Ⅰ) by independent component analysis (ICA), and explore the correlation between abnormal SMN and clinical symptoms.Methods:Eighteen patients with BD-Ⅰ (BD-Ⅰ group) and 20 matched normal controls (HC group) were included.Both groups received resting state fMRI (rs-fMRI) scanning.Based on ICA-fMRI data, one-sample t-test and two-sample t-test were used to analyze the components of SMN and to explore abnormal brain regions between the two groups.Functional network analysis (FNC) was also used to explore the functional connectivity between SMN and other brain networks.Pearson correlation analysis were conducted by SPSS 17.0 to measure the potential associations between intra-and inter-network functional connectivity and age, education, score of Bech-Rafaelsen mania rating scale (BRMS), score of positive and negative syndrome scale (PANSS) and other indicators. Results:In BD-Ⅰ group, the functional connection in the right paracentral lobule (MIN: x=8, y=-32, z=68, t=4.86, P<0.001) and the right postcentral gyrus (MIN: x=41, y=-26, z=53, t=3.33, P<0.001) in SMN were higher than those in HC group.Compared with HC group, the connectivity value in patients with BD-Ⅰ increased between SMN-DAN (0.247±0.073, -0.078±0.080, t=-2.974, P<0.01, FDR adjusted), while the connectivity value decreased between SMN-DMN(-0.037±0.054, 0.272±0.067, t=3.520, P<0.01, FDR adjusted) and between SMN-rFPN(-0.034±0.055, 0.231±0.070, t=2.939, P<0.01, FDR adjusted). Conclusion:The sensorimotor network of patients with BD-Ⅰ has abnormal functional connections within and between networks, and FC values in some networks are positively correlated with manic symptoms, which may be part of the neural mechanisms of patients with BD-Ⅰ.

Objective:To study the difference in the extraction efficiency of the novel coronavirus (2019-nCoV) nucleic acid by using magnetic beads method, centrifugal column method and one-step method.Methods:On March 5, 2021, 10 throat swabs were collected from the staff working in the nucleic acid sampling room in Department of Clinical Laboratory, Affiliated Taikang Xianlin Drum Tower Hospital, Medical School of Nanjing University. The positive quality control samples were mixed into the swabs and used as mock positive samples. The RNA was extracted from simulated positive samples and their diluted samples by using magnetic beads method, centrifugation column method and one-step method. The purity ( A260/ A280 ratio) and concentration of the nucleic acid obtained were measured by micro-uv photometry, and fluorescence quantitative PCR was performed to compare the CT value and extraction efficiency. The three methods were used to extract the simulated weak positive specimens and to compare the difference of CT values after amplification. The measurement data that followed normal distribution were expressed by xˉ±s, the t test was used for comparing in the same group, and single factor analysis of variance was used for comparing among multiple groups. A P value smaller than 0.05 indicated a significant difference. Results:2019-nCoV nucleic acid extracted by magnetic bead method, centrifugal column method and one-step method could amplify positive results. There was no significant difference between the CT value of RNA amplification extracted by magnetic bead method and one-step method ( t=? 0.995 , P=0.376). The CT values of orf1ab gene amplified by centrifugal column method, magnetic bead method and one-step method were 29.28±0.06, 30.82±0.14 and 29.79±0.01 respectively ( F=11.196 , P=0.041). The CT values of E gene were 28.52±0.40, 27.33±0.78 and 27.38±0.13 respectively ( F=3.407, P=0.169). The CT values of N gene were 28.61±1.02, 27.24±0.20 and 27.25±0.47, respectively ( F=2.880 , P=0.020). The CT values of human genes extracted by centrifugal column method, magnetic bead method and one-step method were 19.68±0.36, 20.14±0.06 and 20.58±0.49 respectively, which was statistically significant ( F=4.904, P=0.048). The CT value of amplified human gene was affected by the dilution of human samples twice. The CT value of undiluted samples was smaller than that of diluted samples twice, with a difference of 2.95±0.22, which was statistically significant ( t=?3.025, P=0.039). The extraction time of one-step method, magnetic bead method and centrifugal column method were (15.00±1.50), (20.00±1.50) and (40.00±5.5) min respectively, and the difference was statistically significant ( F=688 , P=0.027). Conclusions:Magnetic bead method, centrifugal column method and one-step method can be used to extract 2019-nCoV nucleic acid, for the centrifugal column method has a higher extraction efficiency than the magnetic bead method and the one-step method. The one-step method is the fastest, followed by the magnetic bead method and the centrifugal column method. A large number of clinical samples can be processed using the magnetic bead method and one-step method. One-step rapid nucleic acid test can also be performed on samples from emergency and fever clinics. It is not recommended to dilute specimens for testing. In order to improve the detection rate, extracting RNA from highly suspected samples with negative initial nucleic acid test by centrifugal column method is suggested.

Objective:To investigate the expression and significance of Toll-like receptor 4 (TLR4) in renal tissue and peripheral blood of children with idiopathic nephrotic syndrome(INS).Methods:The renal biopsy tissues of 78 children with INS diagnosed in the First Affiliated Hospital of Xinxiang Medical University from October 2015 to June 2018 and normal renal tissues of 21 children (control group 1) were collected, and the expressions of TLR4 in the renal tissue was detected by using immunohistochemical method.The expression of TLR4 in different renal pathological types and clinical types of INS was compared, and the correlation of TLR4 with 24-hour urinary protein and serum albumin was analyzed.The expression levels of TLR4 in peripheral blood of children with INS before and after treatment (active stage and remission stage) and 23 healthy children (control group 2) were detected by enzyme linked immunosorbent assay(ELISA). The serum expression levels of TLR4 in different renal pathological types and clinical types of INS were compared, and the correlation of TLR4 with 24-hour urinary protein and serum albumin was analyzed; The correlation between TLR4 expression in renal tubules and in the serum of children with INS was also analyzed.Results:(1)Compared with the expression of TLR4 in normal renal tissues[(0.93±0.26)%], the expression of TLR4 in glomeruli and interstitium of all pathological types of INS [mesangial proliferative glomerulonephritis (MsPGN): (0.93 ± 0.21)%, focal segmental glomerulosclerosis (FSGS): (1.02±0.25)%, membranous glomerulonephritis(MN): (1.03±0.09)%, minimal change disease(MCD): (1.02±0.27)%]was not significantly different ( F=0.741, P=0.562), but the expression of TLR4 in renal tubules[MCD: (82.94±4.62)%, MN: (63.54±1.98)%, MsPGN(42.32±2.97)%, FSGS: (22.60±2.07)%] was significantly increased ( F=1 929.842, P<0.01), Especially, the expression of TLR4 in renal tubules of MCD type INS was significantly higher than that of MN, MsPG N and FSGS [MCD: (82.94±4.62)%, MN: (63.54±1.98)%, MsPGN: (42.32±2.97)%, FSGS: (22.60±2.07)%], and the differences were statistically significant(all P<0.01). TLR4 expression in renal tubules was the highest in steroid-sensitive nephrotic syndrome (SSNS) type and the lowest in INS patients with steroid-resistant nephrotic syndrome (SRNS) type, and the differences were statistically significant( F=220.951, P<0.01). (2)The expression of serum TLR4 in INS children at the active stage [MsPNG: (143.36±12.99) ng/L, FSGS(75.94±7.29) ng/L, MN(210.22±14.66) ng/L, MCD(283.93±21.58) ng/L]was significantly higher than that in INS children at remission stage [MsPNG: (29.51±4.93) ng/L, FSGS(15.66±3.78) ng/L, MN(45.40±5.73) ng/L, MCD(62.29±7.90) ng/L]and control group 2[(0.69 ± 0.33) ng/L], and the differences were statistically significant(all P<0.01); the expression of serum TLR4 in INS children at remission stage was significantly higher than that in the control group 2 ( F=286.287, P<0.01). TLR4 had the highest expression level in serum of MCD type INS children at active and remission stages, followed by MN and FSGS successively.The expression of serum TLR4 was highest in SSNS and lowest in SRNS, and the differences were statistically significant ( F=147.438, P<0.01). (3)The expression of TLR4 in renal tubules of children with INS[(62.82 ±20.94)%]was positively correlated with the expression of TLR4 in serum[(213.26±73.33) ng/L] ( r=0.852, P< 0.05). The expression levels of TLR4 in renal tubules and serum of INS patients at active stage were positively correlated with 24-hour urinary protein level[(123.05±33.55) mg/kg] ( r=0.401, 0.427, all P<0.05), and negatively correlated with serum albumin level[(19.54±3.55)g/L] ( r=-0.602, -0.617, all P<0.05). Conclusions:The expression of TLR4 in renal tubules and serum of children with INS increases, and may be related to different renal pathological types and clinical types of children with INS, as well as disease activity.