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 investigate the value of ultrasonographic features combined with immunohistochemistry in predicting axillary lymph node metastasis in middle-aged women with breast cancer.Methods A retrospective analysis was conducted on 827 middle-aged female breast cancer patients who underwent surgical treatment at the Affiliated Hospital of Chengde Medical University from June 2017 to June 2023.Ultrasonographic and immunohistochemical information was collected,and the patients were randomly allocated into a training set(579 patients)and a validation set(248 patients).Univariate and multivariate Logistic regression analyses were performed to identify ultrasonographic and immunohistochemical risk factors associated with axillary lymph node metastasis in these patients,and a nomogram model was developed.Receiver operating characteristic curves and calibration curves were established to evaluate the performance of the nomogram model,and clinical decision curves were built to assess the clinical value of the model.Results The maximum diameter,morphology,boundary,calcification,and expression of human epidermal growth facor receptor 2 and Ki-67 in breast cancer lesions were identified as risk factors for predicting axillary lymph node metastasis in middle-aged women.The areas under the curve of the nomogram model on the training and validation sets were 0.747(0.707-0.787)and 0.714(0.647-0.780),respectively.Calibration curves and clinical decision curves indicated good consistency and performance of the model.Conclusion The nomogram model constructed based on ultrasonographic features and immunohistochemistry of the primary breast cancer lesion demonstrates high value in predicting axillary lymph node metastasis in middle-aged women with breast cancer.
Humans ; Female ; Breast Neoplasms/diagnostic imaging* ; Middle Aged ; Lymphatic Metastasis/diagnostic imaging* ; Axilla ; Retrospective Studies ; Nomograms ; Ultrasonography ; Immunohistochemistry ; Lymph Nodes/diagnostic imaging* ; Risk Factors ; Ki-67 Antigen

Objective To analyze the efficacy of two-hole and four-hole laparoscopic surgery in patients with sigmoid carcinoma,and to explore the influencing factors leading to complications.Methods The clinical data of 130 patients with sigmoid carcinoma who underwent laparoscopic surgery in our hospital from October 2020 to December 2022 were analyzed.The patients were divided into groups according to the surgical perforation methods.Sixty-eight patients in two-hole group were treated with two-hole laparoscopic surgery and 62 patients in four-hole group were treated with four-hole laparoscopic surgery.The perioperative indexes,visual analogue scale(VAS)scores and postoperative complications of patients in the two groups were observed and compared,and the influencing factors of complications were analyzed.Results The total incision length,first time to get out of bed,first postoperative exhaust time,postoperative hospital stay and VAS score at each time point after surgery of patients in two-hole group were significantly shorter/lower than those in four-hole group(P<0.05).There was no statistically significant difference in the incidence of complications between the two groups(P>0.05).Univariate analysis showed that there were statistically significant differences in the age,preoperative albumin,operation time,intraoperative blood loss,first time to get out of bed,first postoperative exhaust time,postoperative hospital stay,VAS scores at the 3rd day and 5th days after surgery of patients in the occurrence group and the non-occurrence group(P<0.05).Further Logistic regression analysis showed that operation time and preoperative albumin<35 g/L were the main influencing factors for the occurrence of complications(P<0.05).Conclusion Compared with four-hole laparoscopic surgery,two-hole laparoscopic surgery for patients with sigmoid carcinoma has shorter time of perioperative recovery,less postoperative pain,and no difference was found in postoperative complications between the two methods.Operation time and preoperative albumin level<35 g/L were the main influencing factors for the occurence of complications.

Hallux valgus is a common disorder of the forefeet,and its diagnosis and treatment have always drawn the attention of the practitioners.This article introduced the minimally-invasive diagnosis and treatment system for hallux valgus of integrated traditional Chinese and western medicine,which was established by Professor WEN Jian-Min after more than 40 years of in-depth clinical practice and research based on the theory of yin-yang balance and theory of tendons and bones in traditional Chinese medicine(TCM)and through the combination of modern surgical experience.The minimally-invasive diagnosis and treatment system for hallux valgus embodies the principles of balancing yin and yang,laying equal stress on tendons and bones,unifying the fixation and functional exercises,and treating the fractures and the whole body simultaneously,and includes the key technologies such as minimally-invasive osteotomy for the first metatarsal bone,curtain-wrapped external fixation,perioperative Chinese medicine therapy based on syndrome differentiation,and rehabilitation and nursing of TCM.The system will provide a systematic guide for the standardized minimally-invasive treatment of hallux valgus,and will supply an important approach to the treatment of other orthopedic diseases with integrated traditional Chinese and western medicine.The minimally-invasive diagnosis and treatment system for hallux valgus reflects the scientific research achievements and clinical experience of Professor WEN Jian-Min,which exerts high significance of reference and application value.

AIM: To investigate the effects of ginsenoside Rg1 injection combined with inosine tablets and vitamin B1 on serum brain-derived neurotrophic factor(BDNF), pituitary adenylate cyclase activating polypeptide(PACAP)and clinical efficacy in primary retinitis pigmentosa.METHODS: A total of 50 patients(100 eyes)with primary retinitis pigmentosa who admitted to the Department of Ophthalmology, the Second Affiliated Hospital of Hebei North University from August 2019 to March 2022 were selected as the research object. They were divided into the study group and the control group according to random number table, with 50 eyes in each group. Patients in the control group were treated with inosine tablets and vitamin B1, while patients in the study group were treated with ginsenoside Rg1 injection on the basis of the control group. The expression of BDNF and PACAP in serum, electroretinogram and spectral-domain optical coherence tomography(SD-OCT)were compared before and after treatment, and the retinal thickness(RT), mean deviation(MD), clinical efficacy and safety indexes were compared between the two groups.RESULTS: There were no differences in the MD of the two groups before treatment(t=1.670, P=0.098), while the MD of the study group was significantly lower than that of the control group after treatment(t=3.628, P<0.01). Before treatment, RT with a diameter of 1mm at the circle of macular fovea was compared between the two groups(t=0.108, P=0.914), it was significantly higher than that in the control group after treatment(t=6.125, P<0.01). Before treatment, there was no significant difference in the results of dark adaptation of electroretinogram between the two groups(all P>0.05). After treatment, the results of dark adaptation in the study group were significantly better than those in the control group(all P<0.01). Before treatment, there was no significant difference in the results of electroretinogram adaptation between the two groups(all P>0.05). After treatment, the results of electroretinogram adaptation in the study group were significantly better than those in the control group(all P<0.01). There was no significant difference in BDNF and PACAP between the two groups before treatment(all P>0.05). BDNF and PACAP in the study group were higher than those of the control group after treatment(all P<0.01). After treatment, no adverse reactions were observed in both groups.CONCLUSION: The treatment of patients with primary retinitis pigmentosa with ginsenoside will improve the retinal function and promote the prognosis of the disease by regulating the expression of BDNF and PACAP, and it is highly safe.

AIM: To investigate the protective effect of salvianolic acid B on retina and its influence on angiogenesis in retinal vein occlusion(RVO)injured rats.METHODS: SD rats were randomly divided into control group, model group and salvianolic acid B group, with 10 rats in each group. In addition to the control group, rats in model group and salvianolic acid B group were induced RVO by Bengal red combined with laser photodynamic method. The rats in salvianolic acid B group were intraperitoneally injected with salvianolic acid B 50 mg/(kg·d), while the rats in control group and model group were only given the same amount of normal saline for 21 consecutive days. Fundus fluorescein angiography(FFA)was used to observe the retinal vein structure before and after administration. HE staining was used to observe the pathological changes of rat retina. The retinal function of rats was evaluated by electroretinogram(ERG). The fluorescence expression of vascular endothelial growth factor A(VEGFA)in retina of rats in each group was detected by immunofluorescence staining. The relative expression of HIF-1α, STAT3, p-STAT3 and VEGFA proteins in retinal tissue were detected by Western blotting.RESULTS: Compared with the control group, the blood flow at the retinal obstruction in the model group was recanalized, and the effective collateral circulation was abundant, but the shape was irregular, and there was fluorescence leakage. In salvianolic acid B group, the retinal vein circulation recovered, the shape became regular gradually, and the collateral vessels decreased. The retina of the model group and salvianolic acid B group showed different degrees of pathological damage. At the same time, the amplitude of ERG a wave and b wave, the thickness of retinal total layer(RTL), inner nuclear layer(INL)and outer nuclear layer(ONL)decreased, the fluorescence intensity of VEGFA enhanced, and the relative expression of HIF-1α, p-STAT3 and VEGFA protein increased(P<0.05). Compared with the model group, the retinal histopathological damage of salvianolic acid B rats was alleviated, the amplitude of ERG a-wave and b-wave, the thickness of RTL, INL and ONL were increased, the fluorescence intensity of VEGFA was weakened, and the relative expression of HIF-1α, p-STAT3 and VEGFA proteins was decreased(P<0.05).CONCLUSION: Salvianolic acid B can alleviate the retinal histopathological injury and improve retinal function in RVO rats, which may be related to inhibiting the activation of HIF-1α/STAT3/VEGFA pathway and reducing angiogenesis.

Aim To prepare prostate cancer exosomes containing melittin and observe their uptake by prostate cancer cells. Methods Cells treated with starvation for different time were screened for exosome extraction. Exosomes from PC-3 cells were extracted by ultracentrifugation, and the extracted particles were examined by transmission electron microscopy, nanoparticle tracking analyzer(NTA), and Western blot. Melittin exosome system was prepared by repeated freeze-thaw method, incubation at room temperature as well as electroporation, and the size of encapsulation efficiency was measured by centrifugation. A high-performance liquid chromatography(HPLC)method was applied to assay the content of melittin exosomes(exo-mel). Fluorescence inverted microscopy was employed to evaluate the uptake of melittin exosomes by PC-3 cells, DU145 cells as well as LNCaP cells. Results The results of starvation treatment showed that 24 h starvation treatment was the optimal time point. TEM results showed that the exosomes were round or oval in shape with a distinct membranous structure, and the diameter was around 100 nm. The reagent protein concentration for NTA analysis of exosomes was 0.222 g·L-1. The results of Western blot for the marker proteins of exosomes showed that Alix and CD63 were positively expressed, which indicated that the exosomes could be obtained by starvation culture of PC-3 cells and ultracentrifugation. The results of entrapment efficiency showed that the entrapment efficiency of electroporation method was 17.51% ± 2.39%, that of repeated freeze-thaw method was 11.46% ± 1.02%, and that of room temperature incubation method was 3.93% ± 2.44%. The encapsulation efficiency of electroporation was the highest with significant difference(P<0.05). The uptake assay showed that PC-3 cells could efficiently take up exo-mel in a time-dependent manner, and DU145 cells and LNCaP cells also could take up exo-mel over time. Conclusions Exosomes can be accessed by starvation treatment and high-speed centrifugation, and the prostate cancer melittin exosome system prepared by electroporation method could be taken up by prostate cancer cells.

AIM: To explore the efficacy of Danshen injection iontophoresis in the treatment of retinal vein occlusion(RVO).METHODS: The clinical data of 90 patients(90 eyes)with RVO treated in our hospital from January 2020 to December 2021 were analyzed retrospectively, and they were divided into control group and observation group according to treatment methods. A total of 38 patients(38 eyes)in the control group were treated with intravenous Xueshuantong+oral compound Xueshuantong capsule+enteric-coated aspirin, and 52 patients(52 eyes)in the observation group were treated with Danshen injection iontophoresis on this basis. The treatment time of the two groups was 3mo. The clinical efficacy, best corrected visual acuity, retinal condition and hemorheological indexes(whole blood low shear viscosity, fibrinogen)were compared between the two groups before and after treatment.RESULTS: The total effective rate of the observation group was significantly higher than that in the control group(87% vs 58%,P<0.05)at 3mo after treatment. The best corrected visual acuity in both groups was better than that before treatment, and the observation group was better than the control group(all P<0.05).The circulation time of retinal vein, the relative diameter of retinal vein and the relative area of retinal hemorrhage in the observation group were lower than those before treatment,and the observation group was lower than the control group(all P<0.05). The whole blood low shear viscosity and fibrinogen levels in the two groups were lower than those before treatment, and the observation group was lower than those in the control group(all P<0.05).CONCLUSION: Danshen injection iontophoresis is effective in the treatment of patients with RVO, which can effectively improve the visual acuity, treat fundus lesions and improve the abnormal blood flow.

Influenza is an infectious respiratory disease caused by the influenza viruses. Older people, infants and people with underlying medical conditions could have a higher risk of severe influenza symptoms and complications. The co-infection of Coronavirus Diseases 2019 (COVID-19) with influenza viruses could lead to the complication of prevention, diagnosis, control, treatment, and recovery of COVID-19. Influenza vaccine and COVID-19 vaccine overlapped in target populations, vaccination time, and inoculation units. Although there was insufficient evidence on the immunogenicity and safety of co-administration of influenza vaccine and COVID-19 vaccine, World Health Organization and some countries recommended co-administration of inactivated influenza vaccine and COVID-19 vaccine. This review summarized domestic and international vaccination policies and research progress, and put forward corresponding suggestions in order to provide scientific support for the formulation of vaccination strategy on seasonal influenza vaccine and COVID-19 vaccine.
Aged ; COVID-19 ; COVID-19 Vaccines ; China ; Humans ; Infant ; Influenza Vaccines ; Influenza, Human/prevention & control* ; Pandemics/prevention & control* ; SARS-CoV-2 ; Seasons ; Vaccination

Recent population studies have significantly advanced our understanding of how age shapes the gut microbiota.However,the actual role of age could be inevitably confounded due to the complex and variable environmental factors in human populations.A well-controlled envi-ronment is thus necessary to reduce undesirable confounding effects,and recapitulate age-dependent changes in the gut microbiota of healthy primates.Herein we performed 16S rRNA gene sequenc-ing,characterized the age-associated gut microbial profiles from infant to elderly crab-eating maca-ques reared in captivity,and systemically revealed the lifelong dynamic changes of the primate gut microbiota.While the most significant age-associated taxa were mainly found as commensals such as Faecalibacterium,the abundance of a group of suspicious pathogens such as Helicobacter was exclusively increased in infants,underlining their potential role in host development.Importantly,topology analysis indicated that the network connectivity of gut microbiota was even more age-dependent than taxonomic diversity,and its tremendous decline with age could probably be linked to healthy aging.Moreover,we identified key driver microbes responsible for such age-dependent network changes,which were further linked to altered metabolic functions of lipids,carbohydrates,and amino acids,as well as phenotypes in the microbial community.The current study thus demon-strates the lifelong age-dependent changes and their driver microbes in the primate gut microbiota,and provides new insights into their roles in the development and healthy aging of their hosts.