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 effect of mirror therapy on upper limb function and cortical activity in patients with type I complex regional pain syndrome(CRPS)after stroke. Methods A total of 72 post-stroke patients with type I CRPS were recruited at the Third Rehabilitation Hospital Affiliat-ed to Shanghai University of Traditional Chinese Medicine from October,2017 to February,2022.They were ran-domly divided into control group(n=36)and mirror therapy group(n=36).The control group received conven-tional rehabilitation training,while the mirror therapy group received mirror therapy in addition.Before treat-ment,as well as at three and six weeks after treatment,they were evaluated using the Visual Analog Scale(VAS)for pain,modified Barthel Index(MBI),edema volume and Brunnstrom stage.Resting-state data were collected for 440 seconds using a 32-channel functional near-infrared spectroscopy(fNIRS)system. Results After treatment,VAS scores significantly improved in each group,showing better after six weeks than after three weeks(P<0.01).The mirror therapy group was better than the control group after six weeks(P<0.05).MBI scores also significantly improved in each group,showing better after six weeks than after three weeks(P<0.001).Edema volume significantly decreased in each group(Z>30.113,P<0.001),while the mirror therapy group was better than the control group after six weeks(Z=-3.347,P=0.001).Edema volume in the mirror therapy group significantly reduced at both three and six weeks(Z<-0.667,P<0.01),with a stronger effect ob-served after six weeks(Z=-0.667,P=0.005).Brunnstrom stages improved significantly in each group(Z>29.714,P<0.001),while the mirror therapy group was better than the control group after six weeks(Z=-2.046,P=0.041).After treatment,the control group showed strong connectivity between right M1 and right primary so-matosensory cortex,while the mirror therapy group demonstrated stronger connectivity between left M1 and right M1,right primary somatosensory cortex,right pre-motor and supplementary motor cortex.Connectivity be-tween left and right primary somatosensory cortex increased in mirror therapy group,as well as the connectivity between left pre-motor-supplementary motor cortex and right M1,right pre-motor-supplementary motor cortex and left primary somatosensory cortex,left M1 and left primary somatosensory cortex,and left primary somato-sensory cortex and right M1(∣t∣>3.402,P<0.01). Conclusion Mirror therapy may relieve pain and edema,and improve upper limb motor function in post-stroke patients with type I CRPS,which may associate with stonger connectivity between sensory regions on the unaffected side and sensory-motor regions on the affected side,promoting sensorimotor cortical reorganization.

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*

Objective: To analyze the association of fasting plasma glucose (FPG) with mild cognitive impairment (MCI) in the Chinese middle-aged and elderly population from four provinces. Methods: Data were drawn from the baseline data of the Community-based Cohort Study on Nervous System Disease 2018-2019. We selected 3 272 subjects aged 55 and above with completed information on demographics, lifestyle, disease history, cognitive test, psychological assessment, and bio-chemistries measurement, and who were capable of performing basic activities of daily living but without Alzheimer's disease during recruitment. A multivariate logistic regression model was employed to analyze the association between FPG and MCI. Results: Median level of FPG in the study population was 5.5 mmol/L. The prevalence of MCI was 24.8%, and those in groups of the FPG quintile were 19.4%, 22.2%, 29.2%, 26.6%, and 26.1%, respectively, which significantly increased the trend (P=0.002). After adjustment of confounders, multivariate logistic regression analysis found that the MCI risk of subjects in the Q₃,Q₄ and Q₅ groups was 1.641 (95%CI: 1.226-2.131), 1.373 (95%CI: 1.036-1.825), 1.402 (95%CI: 1.054-1.871) times as high as that in the Q₁ group, respectively. Conclusion: High FPG level might serve as a risk factor for MCI in the middle-aged and elderly population, suggesting the importance of monitoring and controlling plasma glucose even without diabetes.
Middle Aged ; Humans ; Aged ; Fasting ; Blood Glucose ; Activities of Daily Living ; Cohort Studies ; Cognitive Dysfunction/epidemiology* ; China/epidemiology*

OBJECTIVE: To observe the effect of electroacupuncture (EA) on expression of interleukin (IL) -23/IL-17 axis and Toll-like receptor 4 (TLR4) in the infarcted tissue in rats with myocardial infarction (MI), and to explore the mechanism of EA on alleviating MI injury. METHODS: Forty male SD rats were randomly divided into a sham-operation group, a sham-operation plus EA group, a model group and an EA group, 10 rats in each group. The MI models were established by ligation of left anterior descending coronary artery in the model group and EA group, while only threading was performed in the sham-operation group and sham-operation plus EA group. The rats in the sham-operation plus EA group and EA group were treated with EA at "Neiguan" (PC 6), disperse-dense wave, 2 Hz/100 Hz, 2 mA, once a day, 20 min each time, for 3 days. After the intervention, the ejection fraction (EF) was measured by echocardiography to evaluate the cardiac function; the infarct area was measured by TTC staining; the HE staining was used to observe the morphological changes of myocardial tissue; the levels of IL-23 and IL-17 in infarcted tissue were detected by ELISA; the protein expression of TLR4 in infarcted tissue was detected by Western blot. RESULTS: Compared with the sham-operation group, the EF was decreased ( CONCLUSION EA may alleviate the excessive inflammatory response after MI by inhibiting the expression of IL-23/IL-17 axis in MI rats, and TLR4 may be involved during the process.
Animals ; Electroacupuncture ; Interleukin-17/genetics* ; Interleukin-23/genetics* ; Male ; Myocardial Infarction/therapy* ; Rats ; Rats, Sprague-Dawley ; Toll-Like Receptor 4/genetics*

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on cardiac function and cardiomyocyte apoptosis in rats with acute myocardial ischemia (AMI), and to explore the correlation between myocardial protective effect of EA and inflammatory factors i.e. interleukin-1β (IL-1β) and interleukin-17 (IL-17) of "Neiguan" (PC 6) area. METHODS: A total of 40 male SD rats with normal ultrasonic cardiogram were randomized into a sham-operation group, a sham-operation plus EA group, a model group and an EA group, 10 rats in each group. The AMI model was established by ligating the left anterior descending (LAD) branch of the coronary artery in the model group and the EA group, while the threading without ligating was adopted in the sham-operation group and the sham-operation plus EA group. In the sham-operation plus EA group and the EA group, EA at bilateral "Neiguan" (PC 6) was applied, with disperse-dense wave, 2 Hz/100 Hz in frequency and 2 mA in density, once a day, 20 min a time for 3 days. The cardiac ejection fraction (EF) and fractional shortening (FS) were measured by ultrasonic cardiogram to evaluate the cardiac function, the cardiomyocyte apoptosis was detected by TUNEL staining, the infiltration of inflammatory factors of "Neiguan" (PC 6) area was observed by H.E. staining, the expression of inflammatory factors IL-1β and IL-17 of "Neiguan" (PC 6) area was detected by immunofluorescence staining. RESULTS: Compared with the sham-operation group, EF and FS were decreased ( CONCLUSION Electroacupuncture at "Neiguan" (PC 6) can improve the cardiac function and reduce the apoptosis of cardiomyocyte in rats with acute myocardial ischemia, its mechanism may be related to the regulation of the inflammatory factors of "Neiguan" (PC 6) area.
Acupuncture Points ; Animals ; Electroacupuncture ; Male ; Myocardial Ischemia/therapy* ; Myocardium ; Rats ; Rats, Sprague-Dawley

ObjectiveTo explore the prevalence rate and related risk factors of anxiety， depression and insomnia symptoms in close contacts of COVID-19 patients undergoing centralized quarantine and observation， so as to provide references for follow-up targeted psychological crisis intervention. MethodsFrom February 6 to 8， 2020， a total of 136 close contacts at designated quarantine sites in four districts and counties of Ya'an city were enrolled， and assessed using the general information questionnaire， Hospital Anxiety and Depression Scale （HAD） and Insomnia Severity Index （ISI）. ResultsA total of 26 quarantined individuals （19.12%） had various degrees of anxiety， depression or insomnia， including 16 cases （11.76%） with anxiety， 9 cases （6.62%） with depression and 16 cases （11.76%） with insomnia. Correlation analysis showed that HAD （A） score was positively correlated with HAD （D） score （r=0.642， P<0.01）. HAD （A） score was positively correlated with ISI score （r=0.590， P<0.01）. HAD （D） score was positively correlated with ISI score （r=0.329， P<0.01）. Multivariate Logistic regression analysis showed that the risk factor of anxiety was the first week of isolation （OR=3.290， P<0.05）， meantime， the risk factors of insomnia included the old age （OR=7.990， P<0.05） and the first week of isolation （OR=4.659， P<0.05）. ConclusionThe close contacts of COVID-19 infections undergoing centralized quarantine and observation in Ya’an have high prevalence rate of anxiety and insomnia， and the symptoms are most severe during the first week of quarantine.

Perilla frutescens,an annual plant in Labiatae family,is grown throughout China and can be used for medicine purposes and as food additives. The present field experiment was carried out to study the effects of different fertilizer treatments on the concentrations and accumulations of antioxidant components,including flavonoids and polyphenols,growth,seed yields and qualities of this plant.The main aim of this study is to provide farmers some advice for improving the yields and qualities of P. frutescens in theory and practice.Five treatments were set up,including a no fertilizer control(CK),chemical fertilizers(CF),organic fertilizers(M),organic fertilizers plus chemical fertilizers at the rates of 1 ∶1 and 1 ∶3 in terms of nitrogen(50 M,25 M). Plant growth parameters were recorded and total flavonoids and polyphenols were determined in three key growth stages of P. frutescens. At the fast growth period,samples of roots,leaves,and stems were collected for determining a total of flavonoids and polyphenols as well as DPPH removal rate of ethanol extracts. Seed yields and qualities were also recorded at harvest. The results showed fertilization enhanced growth and seed yields although no significant difference was observed in growth and seed yields in inorganic-organic fertilizer treatments. The total flavonoids,polyphenols,and DPPH removal rate of ethanol extracts followed the sequence leaves>stems>roots,indicating synthesis of these metabolites in the leaves. DPPH removal rate showed a positive linear correlation with total flavonoid and polyphenol concentrations. In addition,organic-inorganic fertilization significantly increased the numbers of both effective panicles and paniclegrains. Fertilizer treatments had no effect on seed qualities of P. frutescens,while 50 M achieved the highest yield,which increased by 14. 73% compared to CF alone. In general,50 M increased antioxidant components,biomass,and seed yield of P. frutescens,meriting advocate in cultivation.
China ; Fertilizers ; Nitrogen ; Perilla frutescens ; Plant Leaves ; Seeds ; Soil

Objective: To introduce the experience in skin defect reconstruction with keystone design perforator flap. Methods: From January 2012 to December 2012, 26 patients with different types of skin defect were repaired with keystone design perforator flaps, including 21 classic keystone design perforator flaps, 3 short incision keystone design perforator flaps, and 2 Omega variant keystone design perforator flaps. Results: One patient suffered partial flap loss and healed secondarily. All other patients recovered smoothly without complications. Conclusions Keystone design perforator flap offers a versatile technique for skin defect reconstruction except for scalp.

OBJECTIVE To explore the effect of connexin (Cx) 40-formed gap junctional intercellular communication (GJIC) on Photofrin- photodynamic therapy (PDT) phototoxicity in Cx40- transfected HeLa cells and its potential mechanisms. METHODS HeLa cell line stably transfected to express Cx40 was seeded at high and low cell density, respectively, to assess in vitro photosensitivity using CCK8 assay. Western blot assay was performed to detect the expression of Cx40. The intracellular ROS and Ca2 +concentrations were determined using flow cytometer. 4-HNE and ceramide were measured using ELISA assay. RESULTS Cx40-composed GJ formation at high density enhances the phototoxicity of Photofrin-PDT. When the Cx40 is not expressed or Cx40 channels are blocked, the phototoxicity in high-density cultures substantially reduces, indicating that the enhanced PDT phototoxicity at high density is mediated by Cx40-composed GJIC. The GJIC-mediated increase in PDT phototoxicity was associated with ROS and calcium-mediated stress signaling pathways. CONCLUSION The work uniquely presents the ability of Cx40-composed GJIC to enhance the sensitivity of malignant cells to PDT, and indicates that mainte?nance or increase of Cx40-formed GJIC may be a profitable strategy towards the enhancement of PDT therapeutic efficiency.