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*

Aim To research the neuroprotective effect of Haikun Shenxi (HKSX) medicated serum on N2a/ App695 cells and the underlying mechanism. Methods HKSX medicated serum was prepared and carbohydrate components in it was analyzed using high performance thin layer chromatography (HPTLC) . N2a/ App695 cells were intervened with HKSX medicated serum, the cytotoxicity of HKSX medicated serum was measured by MTT; AP[_

We reported a 59-year-old male with exertional angina pectoris, and the coronary angiography showed multiple vessel lesions. The initial strategy was coronary artery bypass grafting (CABG). The measurement of quantitative flow ration (QFR) before operation indicated that the posterior descending branch (PD) did not need to be treated. The left circumflex branch (LCX) was small, and the QFR of the left anterior descending branch (LAD) and the first diagonal branch (D1) was<0.8. Therefore, the LAD and D1 were re-vascularized. The operation strategy was changed to on-pump CABG through a small incision, and the final strategy was LIMA-D1-LAD (sequential), fractional flow reserve (FFR) of distal LAD and D1 after CABG were>0.8 by computed tomography FFR. SYNTAX scores after CABG were 20 and the functional SYNTAX scores after CABG were 3, indicating a good prognosis.

Objective To explore clinical effect and safety of N-acetyl cysteine(NAC)effervescent tablet combined with budesonide and formoterol fumarate powder for inhalation in the treatment of patients with moderate to severe chronic obstructive pulmonary disease(COPD).Methods Patients with moderate to severe COPD were randomly divided into NAC group,ST group and combination group.NAC group was treated with NAC effervescent tablets[NAC effervescent tablets 0.6 g was dissolved in warm water(≤40 ℃),one tablet/once,qd,take medicine at night],ST group was treated with budesonide and formoterol fumarate powder for inhalation(a inhalation/once,bid),combination group was treated with NAC effervescent tablets and budesonide and formoterol fumarate powder for inhalation.All patients were treated for 7 d.The clinical curative effect,peak expiratory flow(PEF),forced expiratory volume in 1 s(FEV1),FEV1/forced vital capacity(FVC),serum CRP,PCT,SAA,6 min walking test(6MWT)and safety in the three groups were evaluated.Results There were 40 cases in each group.After 7 d of treatment,total response rates of NAC group,ST group and combination group were 77.50％(31 cases/40 cases),80.00％(32 cases/40 cases)and 95.00％(38 cases/40 cases),the differences between combination group and NAC group or between combination group and ST group were statistically significant(P＜0.05),but the difference between NAC group and ST group was not statistically significant(P＞0.05).After 7 d of treatment,FVC levels in NAC group,ST group and combination group were(2.51±0.72),(2.59±0.76)and(3.01±0.82)L,PaO2 levels were(2.24±0.61),(2.29±0.64)and(2.87±0.72)L,FEV1/FVC levels were(89.24±4.28)％,(88.42±4.19)％and(95.35±4.27)％,levels of serum CRP were(19.52±2.12),(19.34±2.09)and(11.85±2.24)mg·L-1,PCT levels were(0.83±0.22),(0.87±0.24)and(0.51±0.13)μg·L-1,SAA levels were(28.95±3.48),(29.23±3.75)and(17.70±2.73)mg·L-1,the differences between combination group and NAC group or between combination group and ST group were statistically significant(all P＜0.05),but the difference between NAC group and ST group was not statistically significant(all P＞0.05).The adverse drug reactions were mainly on abdominal pain,diarrhea,headache,nausea and vomiting in the three groups.The total incidence of adverse drug reactions in NAC group,ST group and combination group was 2.50％,5.00％and 12.50％,the difference among the three groups was not statistically significant(all P＞0.05).Conclusion The curative effect of NAC effervescent tablet combined with budesonide and formoterol fumarate powder for inhalation is significant in patients with moderate to severe COPD,which can effectively improve pulmonary function,reduce levels of serum CRP,PCT and SAA,with good safety.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

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.

AIM To explore the ameliorative effects of Ziyin Mingmu Pills on mouse retinitis pigmentosa(RP)and the possible mechanism.METHODS The RP transgenic mice(rd10)were randomly divided into the model group,the Leding group(0.15 g/kg)and the low and high dose Ziyin Mingmu Pills groups(4.50,9.00 g/kg),in contrast to the C57BL/6 mice of the normal group,with 12 mice in each group.The mice had their retinal pathological changes detected by HE staining;their visual function detected by electroretinogram(ERG);their fundus conditions and retinal thickness detected by optical coherence tomography(OCT);their retinal blood perfusion detected by laser speckle blood flow technique;their mRNA expressions of Shh,Ptc,Smo,Gli1,N-myc and Cyclin mRNA detected by digital PCR;and their protein expressions of Shh,Ptc,Smo,Gli1,N-myc and Cyclin detected by immunofluorescence staining.RESULTS Compared with the normal group,the model group displayed pathological changes in the fundus and retina and decreased amplitudes of ERG a wave and b wave(P＜0.01);decreased retinal thickness(P＜0.01);decreased retinal blood perfusion(P＜0.01);and decreased retinal expressions of Shh,Ptc,Smo,Gli1,N-myc,Cyclin mRNA and protein(P＜0.01).Compared with the model group,the groups intervened with Ziyin Mingmu Pills or Leding shared improved pathological changes in the fundus and retina tissue,and increased retinal thickness(P＜0.01);increased retinal blood flow(P＜0.01);increased amplitudes of ERG a wave and b wave(P＜0.01);and increased retinal Shh,Ptc,Smo,Gli1,N-myc and Cyclin mRNA and protein expressions(P＜0.01).CONCLUSION Ziyin Mingmu Pills can improve the fundus pathological changes and visual function to delay RP in mice because of their efficacy in ameliorating retinal thickness and blood flow possibly by activating Shh signaling pathway.

Objective To investigate the feasibility and value of a multi-parametric MRI radiomics-based nomogram model for pretreatment predicting the lymphovascular space invasion(LVSI)of endometrial endometrioid adenocarcinoma(EEA).Methods Preoperative MRI and baseline clinical characteristics of 205 EEA patients were prospectively collected from Oct 2020 to Jan 2022 in the Obstetrics and Gynecology Hospital,Fudan University,and randomly divided into training set(n=123)and validation set(n=82)in a 6∶4 ratio.The whole-tumor region of interest was manually drawn on T2-weighted imaging,diffusion-weighted imaging(apparent diffusion coefficient),and dynamic contrast-enhanced MRI,respectively,for radiomics features extraction.In the training set,univariate and multivariate Logistic regression analysis were used to select independent clinical predictors of LVSI(+)and construct the clinical model.The least absolute shrinkage and selection operator(LASSO)regression and multivariate Logistic regression analysis were used to select optimal radiomics features to form a radiomics signature.A combined nomogram model was established by integrating clinical independent predictors and the radiomics signature,and validated in the validation set.The predicting performance and clinical net benefit were evaluated by using the area under the receiver operating characteristic curve(AUC)and clinical decision curve analysis,respectively.Results Of the 205 EEA cases,144 cases were LVSI(-)and 61 cases were LVSI(+).Menopausal status,CA125,and CA199 were independent clinical predictors for the LVSI(+),and contributing to a clinical model with AUCs of 0.714(training)and 0.731(validation).From 8 240 extracted radiomics features,five were selected to construct a MRI radiomics signature after de-redundancy and LASSO dimensionality reduction,yielding AUCs of 0.860(training)and 0.759(validation).The combined nomogram model showed AUCs of 0.887(training)and 0.807(validation),outperforming others and achieving maximum clinical benefit in a large range of threshold probability in both training and validation sets.Conclusion The multi-parametric MRI-based nomogram model has the potential for pretreatment predicting the LVSI status of EEA,providing valuable information for clinical management decision-making and improving patient's clinical benefits.