Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

OBJECTIVE: To explore the effect of bear bile powder (BBP) on acute lung injury (ALI) and the underlying mechanism. METHODS: The chemical constituents of BBP were analyzed by ultra-high-pressure liquid chromatography-mass spectrometry (UPLC-MS). After 7 days of adaptive feeding, 50 mice were randomly divided into 5 groups by a random number table (n=10): normal control (NC), lipopolysaccharide (LPS), dexamethasone (Dex), low-, and high-dose BBP groups. The dosing cycle was 9 days. On the 12th and 14th days, 20 µL of Staphylococcus aureus solution (bacterial concentration of 1 × 10^-7 CFU/mL) was given by nasal drip after 1 h of intragastric administration, and the mice in the NC group was given the same dose of phosphated buffered saline (PBS) solution. On the 16th day, after 1 h intragastric administration, 100 µL of LPS solution (1 mg/mL) was given by tracheal intubation, and the same dose of PBS solution was given to the NC group. Lung tissue was obtained to measure the myeloperoxidase (MPO) activity, the lung wet/dry weight ratio and expressions of CD14 and other related proteins. The lower lobe of the right lung was obtained for pathological examination. The concentrations of inflammatory cytokines including interleukin (IL)-6, tumour necrosis factor α (TNF-α ) and IL-1β in the bronchoalveolar lavage fluid (BALF) were detected by enzyme linked immunosorbent assay, and the number of neutrophils was counted. The colonic contents of the mice were analyzed by 16 sRNA technique and the contents of short-chain fatty acids (SCFAs) were measured by gas chromatograph-mass spectrometer (GC-MS). RESULTS: UPLC-MS revealed that the chemical components of BBP samples were mainly tauroursodeoxycholic acid and taurochenodeoxycholic acid sodium salt. BBP reduced the activity of MPO, concentrations of inflammatory cytokines, and inhibited the expression of CD14 protein, thus suppressing the activation of NF-κB pathway (P<0.05). The lung histopathological results indicated that BBP significantly reduced the degree of neutrophil infiltration, cell shedding, necrosis, and alveolar cavity depression. Moreover, BBP effectively regulated the composition of the intestinal microflora and increased the production of SCFAs, which contributed to its treatment effect (P<0.05). CONCLUSIONS BBP alleviates lung injury in ALI mouse through inhibiting activation of NF-κB pathway and decreasing expression of CD14 protein. BBP may promote recovery of ALI by improving the structure of intestinal flora and enhancing metabolic function of intestinal flora.
Animals ; Acute Lung Injury/pathology* ; Lipopolysaccharides ; Ursidae ; Gastrointestinal Microbiome/drug effects* ; Bile/chemistry* ; Lipopolysaccharide Receptors/metabolism* ; Powders ; Male ; Lung/drug effects* ; Mice ; Peroxidase/metabolism* ; Signal Transduction/drug effects* ; Cytokines/metabolism*

Objective To explore the computed tomography angiography(CTA)and clinical features of Takayasu's arteritis(TA)with peripheral artery involvement.Methods In this retrospective study,CTA scan was performed in a total of 184 TA patients.TA patients were divided into two groups:60 patients within peripheral artery involvement(peripheral artery involvement group)and 124 patients without peripheral artery involvement(peripheral artery non-involvement group).The difference in comparison of clini-cal data and CTA findings were analyzed.Results A total of 194 peripheral arteries were involved in 60 patients.The most suscep-tible peripheral artery were axillary artery(52,26.8％),middle cerebral artery(26,13.4％)and femoral artery(22,11.3％).In the peripheral artery involvement group,the most common CTA manifestation was luminal stenosis(141,72.7％).The lumen dilata-tion,lumen stenosis with dilatation and wall calcification were not easy to be observed.The age and duration of disease in peripheral artery involvement group were significantly greater than those in peripheral artery non-involvement group(P＜0.05).The proportion of the peripheral artery involvement group in the active phase was significantly lower than that of the peripheral artery non-involvement group(P＜0.05).The incidence of pain in the limbs in peripheral artery involvement group was significantly higher than that in peripheral artery non-involvement group(P＜0.05).The utilization rate of tocilizumab in the peripheral artery involvement group was significantly higher than that in the peripheral artery non-involvement group(P＜0.05).Conclusion TA involving peripheral arteries is more common in patients with a long course of disease and in the inactive phase.Patients are prone to pain in their limbs.The CT A manifestations of these patients are also special,that is,the involved peripheral arteries are not prone to lumen dilatation and wall calcification.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.

Abstract: Objective To analyze the application effect of rapid diagnostic techniques in Shaanxi from 2016 to 2020,and to provide basis for further optimizing the process of tuberculosis detection and formulating prevention and control strategies. Methods A total of 104 437 cases of tuberculosis patients registered in Shaanxi Province from 2016-2020 were exported from the Tuberculosis Information Management System (The subsystem of China Disease Prevention and Control Information System) according to first management unit, and the laboratory test results of sputum smear, sputum culture and molecular tests were collected to statistically analyzed the positive rate of etiology, sputum smear, sputum culture, molecular biology testing rate, and indicators of positive testing rate of tuberculosis patients. Results From 2016 to 2020, the etiology�positive rate of tuberculosis in Shaanxi province were 13.49% (2 664/19 754), 22.68% (5 081/22 401), 35.99% (8 232/22 876), 48.14% (10 438 / 21 682), 52.65% (9 332 / 17 724), respectively, with an increasing trend (χ2 trend=9 473.12, P<0.001) year by year; the proportion of molecular tests positive only in etiology-positive pulmonary tuberculosis (PTB) were 0 (0/2 664), 0.16% (8/5 081), 15.44% (1 271/8 232), 27.58% (2 879/10 438), 31.52% (2 941/9 332), respectively, with an increasing trend year by year (χ2 trend=2 971.44, P<0.001); the molecular test rates of the 5 years were 0.01% (2 / 19 754), 0.38%(85 / 22 401), 21.11% (4 828/22 876), 52.42%(11 365/21 682), 55.18%(9 780/17 724), respectively, with an increasing trend year by year (χ2 trend = 28 269.23, P<0.001). The rate of molecular test in sputum smear-negative was 22.72%(17 976 / 79 130). The proportion of patients with only molecular test-positive was 33.43% (4 032/12 062) in municipal designated hospitals, and 11.99%(2 279/ 19 014) in county-level designated hospitals, the difference was statistically significant (χ2 =2 096.46, P<0.001). Conclusions The rate of molecular biology testing in Shaanxi Province from 2016 to 2020 showed a year-on-year increase. Through the application of rapid molecular tests, the etiology-positive rates of tuberculosis have been increased significantly,but the current molecular test detection rate is not high compared with other provinces, especially in county-level designated hospitals and smear-negative patients, so we should make a big promotion in application of rapid molecular technique.

OBJECTIVE: To explore the influence of lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) on the prognosis of patients with extranodal NK/T cell lymphoma (ENKTL). METHODS: The clinical data of 203 patients with ENKTL admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to January 2020 were retrospectively analyzed. The ROC curve determined the limit values of LMR and NLR; Categorical variables were compared using a chi-square test, expressed as frequency and percentage (n,%). Continuous variables were expressed as medians and extremes and compared with the Mann-Whitney U test; Progression-free survival (PFS) and overall survival (OS) of different grouped LMR and NLR patients were analyzed using Kaplan-Meier curves and compared with log-rank tests. The COX proportional risk regression model was used to perform one-factor and multi-factor analysis of PFS and OS. RESULTS: The optimal critical values of LMR and NLR were determined by the ROC curve, which were 2.60 and 3.40, respectively. LMR≤2.60 was more likely to occur in patients with bone marrow invasion (P=0.029) and higher LDH (P=0.036), while NLR≥3.40 was more likely to occur in patients with higher ECOG scores (P=0.002), higher LDH (P=0.008), higher blood glucose (P=0.024), and lower PLT (P=0.010). Kaplan-Meier survival analysis showed that PFS and OS of patients in the high LMR group were significantly better than the low LMR group, while PFS and OS in the low NLR group were significantly better than the high NLR group. The results of multivariate COX analysis showed that EBV-DNA positive (P=0.047), LMR≤2.60 (P=0.014), NLR≥3.40 (P=0.023) were independent risk factors affecting PFS in patients with ENKTL. LMR≤2.60 (P<0.001), NLR≥3.40 (P=0.048), and high β2-MG (P=0.013) were independent risk factors affecting OS in patients with ENKTL. CONCLUSION Low LMR and high NLR before treatment are associated with poor prognosis in patients with ENKTL, which also can be used as an easily testable, inexpensive, and practical prognostic indicator in the clinic.
Humans ; Monocytes/pathology* ; Neutrophils ; Lymphoma, Extranodal NK-T-Cell/pathology* ; Retrospective Studies ; Lymphocytes ; Prognosis

This study evaluated the scientific nature and effectiveness of iterative optimization of prevention and control measures for local outbreaks caused by the BA.2 and BA.5.2 COVID-19 strains in Fujian Province in 2022,to provide a scientif-ic basis for responding to future new or recurrent respiratory infectious diseases.According to the theory of infectious disease dynamics,relevant information regarding the local epidemic situation caused by the BA.2 sub-type Omicron virus strain in March 2022 and BA.5.2 sub-type Omicron virus strain in October 2022 in Fujian Province was collected.The susceptible exposed infectious removed(SEIAR)model of COVID-19 infection with a latent period and asymptomatic infected persons was used to analyze the transmission dynam-ics of two local epidemic situations,and evaluate the preven-tion and control effects.The incubation period of the BA.2 epidemic was 3 days(1～9 days),the intergenerational inter-val was 3 days(1～5 days),and the initial Rt was 3.0(95％CI:2.7～3.3).The incubation period of the BA.5.2 epidemic was 2 days(1～6 days),the intergenerational interval was 1 day(0～2 days),and the initial R,was 1.9(95％CI:1.7～2.1).The fittingresults for the BA.2 and BA.5.2 epidemics were good,and no statistical difference was observed between the predic-ted and actual numbers of cases(x2BA.2=31.53,x2BA.5.2=27.88,P＞0.05).If an emergency response had not been initiated,the BA.2 epidemic would have continued to spread andpeak on April 7th,with an estimated 638 035 cases.The BA.5.2 epidemic would have rapidly spread,reaching a peak on November 14th,with an estimated 685 940 cases.If one incubation period were detected early,the scale of the BA.2 epidemic would have decreased by 25.73％;if two incubation periods were detected early,the scale would have decreased by 79.56％,and if one incubation period had been delayed,the scale would have expanded by 13.72％.If one incubation period had been detected early in the BA.5.2 epidemic,the scale would have decreased by 35.04％;if two incubation periods had been detected early,the scale would have decreased by 92.47％;and if one incubation period had been delayed,the scale would have increased by 19.75％.The guiding ideology,and the prevention and control measures for handling two local epidemics were optimized and iterated.Our study indicated that implementing the"four early"measures ef-fectively decreased the scale of the epidemic,and earlier detection was associated with more significant control effects.This study provides valuable information for the prevention and control of new or recurrent respiratory infectious diseases.