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*

Taking lipophagy as the breakthrough point, we explored the mechanism of Zexie Decoction(ZXD) in improving lipid metabolism in the hepatocyte model induced by palmitic acid(PA) and in the animal model induced by high-fat diet(HFD) on the basis of protein kinase B(Akt)/transcription factor EB(TFEB) signaling pathway. Co-localization was carried out for the microtubule-associated protein light chain 3(LC3) plasmid labeled with green fluorescent protein(GFP) and lipid droplets(LDs), and immunofluorescence co-localization for liver LC3 of HFD mice and perilipin 2(PLIN2). The results showed that ZXD up-regulated the expression of LC3, reduced lipid accumulation in hepatocytes, and increased the co-localization of LC3 and LDs, thereby activating lipo-phagy. Western blot results confirmed that ZXD increased autophagy-related protein LC3Ⅱ/LC3Ⅰ transformation ratio and lysosome-associated membrane protein 2(LAMP2) in vivo and in vitro and promoted the degradation of sequestosome-1(SQSTM1/p62)(P<0.05). The results above jointly explained that ZXD regulated lipophagy. Furthermore, ZXD activated TFEB expression(P<0.05) and reversed the PA-and HFD-induced decrease of TFEB nuclear localization in hepatocytes(P<0.05). Meanwhile, ZXD activated liver TFEB to up-regulate the expression of the targets Lamp2, Lc3 B, Bcl2, and Atg5(P<0.05). Additionally, ZXD down-regulated the protein level of p-Akt upstream of TFEB in vivo and in vitro. In conclusion, ZXD may promote lipophagy by regulating the Akt/TFEB pathway.
Animals ; Mice ; Autophagy/drug effects* ; Hepatocytes/metabolism* ; Microtubule-Associated Proteins/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Drugs, Chinese Herbal/pharmacology*

Objective:To analyze the epidemiological characteristics of hepatitis B （HB） in Huzhou from 2004 to 2017 in order to provide theoretical basis for the prevention of HB. Methods:Descriptive epidemiologic methods were used to analyze the data of HB cases in Huzhou city， 2004-2017. Results:A total of 16 685 HB cases were reported in Huzhou from 2004 to 2017. The average annual incidence of HB was 41.58/10⁵. Incidence tended to decrease （χ²=5 094.667， P<0.01）. The incidence of HB among males was higher than that among females （χ²=2 619.143，P<0.01）， and the incidence rate among males and females both tended to decrease （male： χ²= 3 408.813， P<0.01；female： χ²=1 716.388， P<0.01）. Of the reported case of HB， 83.0% involved individuals between 20 and 60 years of age. Most of the patients were farmers， accounting for 52.41% of the total cases. The top three districts reporting high case numbers were Changxing （4 584 cases （27.47%））， Wuxing （4 356 cases （26.11%））， Anji （3 192 cases（19.13%））， while the top county/district of the annual incidence was Changxing （50.10/10⁵）. Conclusion:Incidence of HB kept decreasing between 2004 and 2017 in Huzhou. Adults are the key population vulnerable to HB virus. To further reduce the incidence of HB， it is necessary to strengthen the prevention of HB and HB vaccination rate among high-risk groups.

OBJECTIVE: To investigate the expression level of miR-181b in CD19+ B lymphocytes of patients with chronic lymphocytic leukemia (CLL), to analyze the relationship between its expression and the prognosis of CLL patients, and to predict the potential target gene of miR-181b in CLL by using bioinformatics. METHODS: Eight-four patients with CLL treated in People's Hospital of Xinjiang Uygur Autonomous Region from June 2013 to June 2018 were selected. and 20 healthy people were selected as control group. RNA was extracted from CD19+B lymphocytes of peripheral blood by magnetic bead sorting, the expression level of miR-181b was detected, and it's expression differences in different IPI groups were analyzed. The correlation between the expression level of miR-181b and PFS of CLL patients also was analyzed. miR-181b target genes were predicted by online database and literatures, and gene annotation analysis and relevant signal pathway analysis were performed for candidate target genes. RESULTS: The expression level of miR-181b in CLL patients was significantly lower than that in control group (P＜0.01); The expression level of miR-181b in the low-risk group was higher than that in high-risk group and extremely high-risk group (P＜0.05), but there was no statistical difference between low-risk group and medium-risk group (P=1.00). The expression level of miR-181b in medium-risk group was higher than that in high-risk group and extremely high-risk group (P＜0.05), but there was no difference between high-risk group and extremely high-risk group (P=1.00). ROC curve results showed that the area under the curve (AUC) was 0.792 (P＜0.01).When the expression level of miR-181b was at the threshold value of 0.279, it showed a better sensitivity (62.9%) and specificity (91.8%). Survival analysis results suggested that compared with the high expression group, the miR-181b low expression group had poor PFS (log rank: P=0.047). Prediction of miR-181b by using the starBase, targetscan and picTar database and its combination with literature reports indicated that CARD11, ZFP36L1, RUNX1, NR4A3, ATP1B1, PUM1 and PLAG1 related with blood diseases, and up-regulated CARD11 and ZFP36L1 participated in lymphoid tumor formation by promoting cell proliferation and inhibiting cell aging. CONCLUSION The expression level of miR-181b in CLL group are significantly lower than that in the controls group, and the low expression of miR-181b relates with poor prognosis of CLL patients. Through bioinformatics prediction and combined with literature reports, it is speculated that CARD11 and ZFP36L1 as target genes of miR-181b may be participated in the occurrence and development of CLL. Further experiments are needed to verify this result.
Apoptosis Regulatory Proteins ; Cell Proliferation ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; MicroRNAs ; Prognosis

OBJECTIVE: To observe the therapeutic effect of acupuncture combined with cranial electrotherapy stimulation (CES) on generalized anxiety disorder (GAD). METHODS: A total of 200 patients with GAD were randomized into an acupuncture+CES group, an acupuncture group, a CES group and a medication group, 50 cases in each one. In the medication group, patients were treated with tandospirone citrate tablet orally, 10 mg after breakfast, lunch and dinner respectively. In the CES group, CES was adopted by SCS brain electromedical instrument, 60 min each time, once a day. In the acupuncture group, acupuncture was applied to Baihui (GV 20), Sishencong (EX-HN 1), Yintang (GV 29), Shenting (GV 24), etc., 30 min each time, once a day. In the acupuncture+CES group, CES was adopted before acupuncture. Treatment of sixty days was required in the 4 groups. Before and after treatment, the scores of Hamilton anxiety scale (HAMA), World Health Organization's quality of life questionnaire-brief version (WHOQOL-BREF) and treatment emergent symptom scale (TESS) were observed, the clinical effect was evaluated, and the relapse of anxiety during follow-up of 1 year after treatment was recorded in the 4 groups. RESULTS: Compared before treatment, the scores of HAMA after treatment were decreased ( CONCLUSION Acupuncture combined with CES can effectively relieve the symptoms in patients with GAD, improve the quality of life, reduce the occurrence of adverse reactions and the relapse rate, and its clinical effect is obviously superior to the western medication, the simple application of acupuncture or CES.
Acupuncture Points ; Acupuncture Therapy ; Anxiety Disorders/therapy* ; Electric Stimulation Therapy ; Humans ; Quality of Life ; Treatment Outcome

BACKGROUND: Psoriasis is a common chronic inflammatory skin disease with 2% to 3% prevalence worldwide and a heavy social-psychological burden for patients and their families. As the exact pathogenesis of psoriasis is still unknown, the current treatment is far from satisfactory. Thus, there is an urgent need to find a more effective therapy for this disease. Keratin 17 (K17), a type I intermediate filament, is overexpressed in the psoriatic epidermis and plays a critical pathogenic role by stimulating T cells in psoriasis. Therefore, we hypothesized that inhibiting K17 may be a potential therapeutic approach for psoriasis. This study aimed to investigate the therapeutic effect of K17-specific small interfering RNA (siRNA) on mice with imiquimod (IMQ)-induced psoriasis-like dermatitis. METHODS: Eight-week-old female BALB/c mice were administered a 5% IMQ cream on both ears to produce psoriatic dermatitis. On day 3, K17 siRNA was mixed with an emulsion matrix and applied topically to the left ears of the mice after IMQ application every day for 7 days. The right ears of the mice were treated in parallel with negative control (NC) siRNA. Inflammation was evaluated by gross ear thickness, histopathology, the infiltration of inflammatory cells (CD3+ T cells and neutrophils) using immunofluorescence, and the expression of cytokine production using real-time quantitative polymerase chain reaction. The obtained data were statistically evaluated by unpaired t-tests and a one-way analysis of variance. RESULTS: The severity of IMQ-induced dermatitis on K17 siRNA-treated mice ears was significantly lower than that on NC siRNA-treated mice ears, as evidenced by the alleviated ear inflammation phenotype, including decreased ear thickness, infiltration of inflammatory cells (CD3+ T cells and neutrophils), and inflammatory cytokine/chemokine expression levels (interleukin 17 [IL-17], IL-22, IL-23, C-X-C motif chemokine ligand 1, and C-C motif chemokine ligand 20) (P < 0.05 vs. the Blank or NC siRNA groups). Compared to the NC siRNA treatment, the K17 siRNA treatment resulted in increased K1 and K10 expression, which are characteristic of keratinocyte differentiation (vs. NC siRNA, K17 siRNA1 group: K1, t = 4.782, P = 0.0050; K10, t = 3.365, P = 0.0120; K17 siRNA2 group: K1, t = 4.104, P = 0.0093; K10, t = 4.168, P = 0.0042; siRNA Mix group: K1, t = 3.065, P = 0.0221; K10, t = 10.83, P < 0.0001), and decreased K16 expression, which is characteristic of keratinocyte proliferation (vs. NC siRNA, K17 siRNA1 group: t = 4.156, P = 0.0043; K17 siRNA2 group: t = 2.834, P = 0.0253; siRNA Mix group: t = 2.734, P = 0.0250). CONCLUSIONS Inhibition of K17 expression by its specific siRNA significantly alleviated inflammation in mice with IMQ-induced psoriasis-like dermatitis. Thus, gene therapy targeting K17 may be a potential treatment approach for psoriasis.
Animals ; Dermatitis ; Disease Models, Animal ; Female ; Humans ; Imiquimod ; Inflammation ; Keratin-17/genetics* ; Mice ; Mice, Inbred BALB C ; Psoriasis/genetics* ; RNA, Small Interfering/genetics* ; Skin

Spargana were collected from human and frogs in Liaoning and Hubei Provinces, China. PCR amplification and direct sequencing of A cox1 fragment was PCR-amplified from genomic DNA extracted from 7 specimens (5 from humans and 2 from frogs). The cox1 fragment (390 bp) showed 97–100% similarity to the reference sequence of S. erinaceieuropaei and 88–89% to the reference sequence of S. decipiens. There were 1–12 bases different between these worms, but no obvious genetic variation (0–3.3%) to the references. There was little difference of cox1 gene between sparganum samples of humans and frogs (1–3%). This study is the first report on S. erinaceieuropaei spargana from humans in Liaoning and Hubei Provinces.
China ; DNA ; Genetic Variation ; Humans ; Polymerase Chain Reaction ; Sparganum ; Spirometra

With the development and change of Uygur medicine, The sources,medicinal parts and producing area of some Uygur Medicine have changed. It is more important to master the classification, distribution and change of Uygur medicinal materials. These were more than 1 200 kinds Uygur medicine in history were resaerched by field investigation, philological research, and textual research, which main source of original plant were 140 families, 510 genera, 840 species; and source of original animal were 76 families, 107 genera, the original animal 141 species; 55 kinds of original mineral, which main producer were Xinjiang and Central Asia, West Asia, the Mediterranean, and North Africa, Southeast Asia and other provinces in China, there are individual medicinal materials from the Americas, Europe and other places. Through this study the classification, distribution, source and evolution of specific families and genera of Uygur medicine resources have mastered.It is hoped to provide theoretical basis for further research and development of Uygur medicinal materials.

OBJECTIVETo investigate the relationship between early peak body temperature and neutropenia duration and its potential mechanism.

METHODSA total of 111 patients with CR1 phase acute leukemia (AL) with neutropenia infection were enrolled in this study. The relationship between early peak body temperature and neutropenia duration was analyzed retrospectively, and the IL-6 serum level in patients with different peak of body temperature was detected, and the single cell culture system in vitro was established, the incorparation rate of EdU in vivo was detected, and the effect of IL-6 on mouse hematopoietic stem cells /progenitor cells was analyzed.

RESULTSOut of 111 patients with nentropenia, the body temperature <38 °C and the neutropenia duration 9.5±3.69 d were observed in 44 patients, while the body temperature >38 °C and neutropenia duration 7.33±4.20 d were observed in 69 patients, the differences between 2 groups was statistically signficant (P<0.05). The EdU test showed that the number of EdU hematopoietic stem cells and progenitor cells increased. The IL-6 level was different in patients with different peaks of initial bady temperature (P<0.05). The results of amimal experiment showed that the IL-6 could promote the proliferation of hematopoietic stem cells/ progenitor cells in vitro and in vivo.

CONCLUSIONFor patients with neutropenic infection when initial body temperature peak is <38 °C, the probability of neutropenia duration prolonging after chamotherapy increases, which may relate with promotive effect of pro-inflammatory cytokins on prliferation of hematopoietic stem cells/progenitor cells.