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 design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]

Objectives: In order to provide valuable information for the diagnosis and treatment of dermatitis, the prevalence rate and trend changes of common allergens in patients with allergic skin diseases in Beijing City were investigated and analyzed. Methods: This study was a retrospective data collection study. A total of 2 822 patients diagnosed with moderate to severe atopic dermatitis with allergen examinations were collected from Peking University First Hospital from 2017 to 2021, most of them were adults, and 83%(2 340/2 822) were over 18 years old. The ImmunoCAP fluorescent enzyme-linked immunoassay system was used to quantify specific IgE. The positive rate of each allergen was counted according to age, gender and year. The epidemiological characteristics and trends were analyzed. Results: In the past five years, 22 503 allergen-specific IgE test data were collected, and the positive rate of allergens in 40%(1 122/2 822) of the 2 822 patients was mainly multiple sensitization, the positive rate of allergens and multiple sensitization rates were the highest in people aged 13-18 years old. The 2 822 patients were dominated by inhaled allergens, and the highest positive rate was inhaled mixture (29.3%). The top five positive rates of inhaled allergens were Dermatophagoides farina (26.7%), Dermatophagoides pteronyssinus (25.5%), Mugwort (23.9%), Birch pollen (19.2%) and Siberian cocklebur (18.2%). The top five positive rates of food allergens were shrimp (15.2%), peanut (14.8%), sesame (14.7%), wheat (13.2%) and milk (13.1%). Analysis of the positive rate of allergens in different age groups showed except for the positive rate of birch pollen peaked at 3-12 years old, other inhaled allergens were the highest food allergens in 13-18 years old. Among food allergens, the positive rates of fx5, milk, egg and wheat were the highest in <3 years old, the positive rate decreased gradually with age, and the positive rate of other food allergens peaked at 13-18 years old, and the shrimp and crab was the highest in adult. The positive rate of various allergens in the 2 822 patients showed little difference between male and female and the male was slightly higher than female. In the past five years, the positive rate of allergens has been on the rise. The changes of inhaled allergens in cat/dog hair dander, Dermatophagoides farina and cicadas were large, while the positive rate of food allergens was stable. Conclusions: The etiology of the allergic skin diseases is complex, which may be related to allergen exposure, heredity, immunity, environmental factors, abnormal skin barrier function, etc. This study showed the distribution of allergens in patients with allergic skin diseases in Beijing City to a certain extent. It provided epidemiological data and clinical evidence for the prevention and treatment of allergic diseases.
Adult ; Animals ; Dogs ; Humans ; Female ; Male ; Adolescent ; Child, Preschool ; Child ; Allergens ; Dermatitis, Atopic/epidemiology* ; Retrospective Studies ; Hospitals ; Immunoglobulin E

Objectives: In order to provide valuable information for the diagnosis and treatment of dermatitis, the prevalence rate and trend changes of common allergens in patients with allergic skin diseases in Beijing City were investigated and analyzed. Methods: This study was a retrospective data collection study. A total of 2 822 patients diagnosed with moderate to severe atopic dermatitis with allergen examinations were collected from Peking University First Hospital from 2017 to 2021, most of them were adults, and 83%(2 340/2 822) were over 18 years old. The ImmunoCAP fluorescent enzyme-linked immunoassay system was used to quantify specific IgE. The positive rate of each allergen was counted according to age, gender and year. The epidemiological characteristics and trends were analyzed. Results: In the past five years, 22 503 allergen-specific IgE test data were collected, and the positive rate of allergens in 40%(1 122/2 822) of the 2 822 patients was mainly multiple sensitization, the positive rate of allergens and multiple sensitization rates were the highest in people aged 13-18 years old. The 2 822 patients were dominated by inhaled allergens, and the highest positive rate was inhaled mixture (29.3%). The top five positive rates of inhaled allergens were Dermatophagoides farina (26.7%), Dermatophagoides pteronyssinus (25.5%), Mugwort (23.9%), Birch pollen (19.2%) and Siberian cocklebur (18.2%). The top five positive rates of food allergens were shrimp (15.2%), peanut (14.8%), sesame (14.7%), wheat (13.2%) and milk (13.1%). Analysis of the positive rate of allergens in different age groups showed except for the positive rate of birch pollen peaked at 3-12 years old, other inhaled allergens were the highest food allergens in 13-18 years old. Among food allergens, the positive rates of fx5, milk, egg and wheat were the highest in <3 years old, the positive rate decreased gradually with age, and the positive rate of other food allergens peaked at 13-18 years old, and the shrimp and crab was the highest in adult. The positive rate of various allergens in the 2 822 patients showed little difference between male and female and the male was slightly higher than female. In the past five years, the positive rate of allergens has been on the rise. The changes of inhaled allergens in cat/dog hair dander, Dermatophagoides farina and cicadas were large, while the positive rate of food allergens was stable. Conclusions: The etiology of the allergic skin diseases is complex, which may be related to allergen exposure, heredity, immunity, environmental factors, abnormal skin barrier function, etc. This study showed the distribution of allergens in patients with allergic skin diseases in Beijing City to a certain extent. It provided epidemiological data and clinical evidence for the prevention and treatment of allergic diseases.
Adult ; Animals ; Dogs ; Humans ; Female ; Male ; Adolescent ; Child, Preschool ; Child ; Allergens ; Dermatitis, Atopic/epidemiology* ; Retrospective Studies ; Hospitals ; Immunoglobulin E

This study aimed to investigate the effect of Tibetan medicine Ershiwuwei Songshi Pills(ESP) on the intestinal flora of non-alcoholic steatohepatitis(NASH) mice. Forty-eight male C57 BL/6 mice were randomly divided into the control group, model(methionine-choline-deficient, MCD) group, high-(0.8 g·kg~(-1)), medium-(0.4 g·kg~(-1)), and low-dose(0.2 g·kg~(-1)) ESP groups, and pioglitazone(PGZ, 10 mg·kg~(-1)) group, with eight mice in each group. Mice in the control group were fed with normal diet, while those in the remaining five groups with MCD diet for five weeks for inducing NASH. During modeling, they were gavaged with the corresponding drugs. The changes in body mass, daily water intake, and daily food intake were recorded. At the end of the experiment, the liver tissues were collected and stained with hematoxylin-eosin(HE) for observing the pathological changes, followed by oil red O staining for observing fat accumulation in the liver. The levels of serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) and triglyceride(TG) in liver tissue were measured. The changes in intestinal flora of mice were determined using 16 S rRNA high-throughput sequencing technology. The results showed that compared with the model group, the high-, medium-and low-dose ESP groups and the PGZ group exhibited significantly lowered AST and ALT in serum and TG in liver tissues and alleviated hepatocellular steatosis and fat accumulation in the liver. As demonstrated by 16 S rRNA sequencing, the abundance index and diversity of intestinal flora decreased in the model group, while those increased in the ESP groups. Besides, the Firmicutes to Bacteroidetes ratio decreased at the phylum level. In the alteration of the composition of intestinal flora, ESP reduced the abundance of Erysipelotrichia and Faecalibaculum but increased the abundance of Desulfovibrionaceae, Rikenellaceae, Lachnospiraceae, and Ruminococcaceae. This study has revealed that ESP has a protective effect against NASH induced by MCD diet, which may be related to its regulation of the changes in intestinal flora, alteration of the composition of intestinal flora, and inhibition of the intestinal dysbiosis.
Animals ; Disease Models, Animal ; Gastrointestinal Microbiome ; Liver ; Male ; Medicine, Tibetan Traditional ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/drug therapy*

A chronic cholestasis model was induced in mice by feeding a diet containing 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine(DDC). The effects of Ershiwuwei Songshi Pills(ESP) on endogenous metabolites in mice with chronic cholestasis were investigated by metabolomics analysis based on liquid chromatography-mass spectrometry(LC-MS). The results showed that ESP was effective in improving pathological injury and reducing serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), and total bile acid in the model mice. Meanwhile, 13 common differential metabolites were revealed in metabolomic screening between the model/control group and the model/ESP group, including uric acid, glycolaldehyde, kynurenine, flavin adenine dinucleotide, L-3-phenyllactic acid, I-urobilin, leukotriene D4(LTD4), taurocholic acid, trioxilin A3, D-inositol-1,4-diphosphate, PC [16:0/20:2(11Z,14Z)], PC[14:0/22:2(13Z,16Z)], and PC[20:4(5Z,8Z,11Z,14Z)/20:4(5Z,8Z,11Z,14Z)]. After ESP intervention, the levels of all 13 differential metabolites were significantly retraced, and pathway analysis showed that ESP achieved its therapeutic effect mainly by affecting arachidonic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism, and primary bile acid biosynthesis. This study elucidated the mechanism of action of ESP against chronic cholestasis based on metabolites.
Animals ; Bile Acids and Salts ; Cholestasis/drug therapy* ; Chromatography, Liquid ; Medicine, Tibetan Traditional ; Metabolomics ; Mice

An ideal animal model of azoospermia would be a powerful tool for the evaluation of spermatogonial stem cell (SSC) transplantation. Busulfan has been commonly used to develop such a model, but 30%-87% of mice die when administered an intraperitoneal injection of 40 mg kg^-1. In the present study, hematoxylin and eosin staining, Western blot, immunofluorescence, and quantitative real-time polymerase chain reaction were used to test the effects of busulfan exposure in a mouse model that received two intraperitoneal injections of busulfan at a 3-h interval at different doses (20, 30, and 40 mg kg^-1) on day 36 or a dose of 40 mg kg^-1 at different time points (0, 9, 18, 27, 36, and 63 days). The survival rate of the mice was 100%. When the mice were treated with 40 mg kg^-1 busulfan, dramatic SSC depletion occurred 18 days later and all of the germ cells were cleared by day 36. In addition, the gene expressions of glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factor 2 (FGF2), chemokine (C-X-C Motif) ligand 12 (CXCL12), and colony-stimulating factor 1 (CSF1) were moderately increased by day 36. A 63-day, long-term observation showed the rare restoration of endogenous germ cells in the testes, suggesting that the potential period for SSC transplantation was between day 36 and day 63. Our results demonstrate that the administration of two intraperitoneal injections of busulfan (40 mg kg^-1 in total) at a 3-h interval to mice provided a nonlethal and efficient method for recipient preparation in SSC transplantation and could improve treatments for infertility and the understanding of chemotherapy-induced gonadotoxicity.
Adult Germline Stem Cells/transplantation* ; Animals ; Azoospermia/chemically induced* ; Busulfan/toxicity* ; Disease Models, Animal ; Infertility, Male/chemically induced* ; Injections, Intraperitoneal ; Male ; Mice ; Spermatogenesis/drug effects* ; Spermatogonia/drug effects* ; Stem Cell Transplantation/methods*

The aim of this paper was to investigate the hemostatic effect and mechanism of carbonized Scutellariae Radix on uterine bleeding in the rats caused by early pregnancy termination. Eight unpregnant female rats were selected as normal group. Forty female rats conceived on the same day received mifepristone(11. 4 mg·kg-1) and misoprostol(125 μg·kg-1) to induce model of incomplete abortion in early pregnancy. Abortion models were randomly divided into model group,carbonized Scutellariae Radix water extract low dose group(0. 55 g·kg-1),medium group(1. 10 g·kg-1),high dose group(2. 20 g·kg-1) and positive control group(0. 45 g·kg-1).The uterine bleeding volume was detected by ultraviolet spectrophotometry. The pathological changes of endometrium were detected by HE(hematixylin-eosin) staining. The levels of interleukin(IL-1β),IL-6 and tumor necrosis factor(TNF-α) in the plasma of rats were determined by ELISA. The expression levels of IL-1β,IL-6 and TNF-α mRNA in the uterus of rats were determined by RT-PCR.The protein expression levels of VEGF,MMP-2 and MMP-9 were determined by Western blot. As compared with the normal group,the uterine bleeding volume and histopathological score were increased significantly; microvessel density of endometrial tissues was decreased significantly; the contents of TNF-α,IL-1β and the levels of TNF-α mRNA and IL-1β mRNA in the plasma were increased,while the content of IL-6 and level of IL-6 mRNA were decreased significantly. The protein expression levels of VEGF,MMP-2 and MMP-9 in the uterine tissues were also decreased. As compared with the model group,the uterine bleeding volume was decreased significantly in the carbonized Scutellariae Radix medium dose and high dose groups; endometrial repair was promoted,and the microvessel density of endometrial tissues was increased significantly; the contents of IL-1β and TNF-α in the plasma of rats were decreased significantly,while the content of IL-6 in the plasma of rats was increased significantly; the expression levels of IL-1β and TNF-α mRNA in the uterus of rats were decreased and the expression level of IL-6 mRNA showed an increase; the protein expressions of VEGF,MMP-2 and MMP-9 were decreased significantly in carbonized Scutellariae Radix medium and high dose groups. In conclusion,carbonized Scutellariae Radix showed good hemostatic effect,and its mechanism may be related to the repair of endometrium and inhibition of inflammatory reaction.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Female ; Hemostatics/pharmacology* ; Humans ; Inflammation ; Interleukin-1beta ; Rats ; Scutellaria baicalensis ; Tumor Necrosis Factor-alpha ; Uterine Hemorrhage

Objective To assess the dietary risk of organophosphates pesticides residues in some vegetables in Shaanxi Province. Methods The monitoring data of organophosphorus pesticides in vegetables from 2012 to 2016 were derived from Shaanxi Province Food Contamination Monitoring Network. The exposure of organophosphorus to vegetables by using exposure risk index (ERI) , dietary exposure risk index (RI) and dietary exposure risk assessment. Results Exposed risk index (ERI) of organophosphorus in some vegetables in Shaanxi Province ranged from 1.25E-06 to 1.87E-01, and among them, the highest ERI of clozaptid in garlic was 1.87E-01, followed by onion. In some vegetables, the highest exposure to organophosphorus was isocarbophos of fresh beans with an exposure of 4.27E-02 μg / (kg body weight · day) and the lowest dietary exposure was bulbs, and stems and fresh beans were 2.00E-04μg / (kg body weight·day) . The exposure of organophosphorus to all kinds of vegetables was less than their respective daily allowable intake (ADI) . The risk of dietary exposure to organic- phosphorus in vegetables was 187％ and greater than 100％ for the risk index (RI) of lettuce, and RI for all other vegetables was <100％. Conclusion The dietary exposure and risk index of organophosphates pesticides in some vegetables in Shaanxi Province was safe, and more attention should be paid to dimethoate and isazofos.

Based on the solution-diffusion effect and the charge effect theory in nanofiltration separation, the correlation between initial concentration and mass transfer coefficient was constructed to establish a mathematic model of synephrine in mass transfer process and verify its applicability. The experimental results showed that there was a linear relationship between operation pressure and membrane flux. Meanwhile, the membrane flux was gradually decayed with the increase of solute concentration. Besides, mass transfer coefficient and initial concentration of synephrine showed power function correlation with each other by solution-diffusion effect and the charge effect, and the regression coefficients were greater than 0.9. The mass transfer coefficient of dissociation synephrine was less than that in the state of free and free-dissociation. Moreover, on the basis of power function relationship between mass transfer coefficient and initial concentration, the results showed that the predicted rejections of synephrine from Citrus aurantium water extract by use of the mathematical model approximated well to real ones, verifying that the model was practical and feasible. The unclear separation mechanism of nanofiltration for alkaloids was clarified preliminary by the predicted model of nanofiltration separation with synephrine as the example, providing theoretical and technical support for nanofiltration separation, especially for traditional Chinese medicine with alkaloids.