Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Gut microbiota is a bridge between the metabolism and health state of the host,which plays a very important role in maintaining homeostasis. Natural polysaccharides,widely existed in nature,are a kind of biological macromolecules with prebiotics effects,which can improve a degree of physiological status by selectively changing the gut microbiota structure and function,enhancing the content of short chain fatty acids(SCFAs)and decreasing the level of inflammatory cytokines. In addition,the majority of polysaccharides can be degraded by gut microbiota to enhance their bioavailability and to promote the health state of the host. In this paper we discuss the interaction among polysaccharides and gut microbiotanatural,degradation mechanism and review gut microbiota as a target in the treatment of metabolic diseases,so as to provide future prospects of natural polysaccharides as " prebiotics " functional factors in the field of biological medicine and health products.

This study was designed to determine the metabolites of Zhali Nusi Prescription(ZLNSP) in rats. The ultra-high performance liquid chromatography-LTQ Orbitrap mass spectrometric(UHPLC-LTQ-Orbitrap-MS) and mass defect filter techniques were applied to analyze the metabolites of ZLNSP in rat plasma, bile, urine and feces. The biological samples were analyzed by ACQUITY UPLC BEH T_3 column(2.1 mm×100 mm,1.7 μm), with 0.1% formic acid water(A)-acetonitrile(B) as mobile phase, and the biological samples were analyzed in negative ion mode by electrospray ionization mass spectrometry(ESI-MS). An analytical method for biological samples of rats was established, and 8 prototype components and 36 metabolites were identified. The results showed that the metabolic pathways of the main components of ZLNSP in rats included methylation, glucuronidation, sulfation and so on. It provi-ded information for the therapeutic effect of ZLNSP in vivo.
Administration, Oral ; Animals ; Bile ; Chromatography, High Pressure Liquid ; Feces ; Plasma ; Prescriptions ; Rats

BACKGROUND: Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients. METHODS: From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores. RESULTS: Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation. CONCLUSIONS LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.
Aged ; Betacoronavirus ; Coronavirus Infections ; complications ; mortality ; Extracorporeal Membrane Oxygenation ; Humans ; Lung Transplantation ; methods ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; complications ; mortality ; Pulmonary Fibrosis ; mortality ; surgery ; Respiratory Distress Syndrome, Adult ; mortality ; surgery

Objective To explore the effect of endogenous sulfur dioxide (SO2)on the apoptosis induced by cobalt chloride (CoCl2)in the human pulmonary arterial endothelial cells (HPAECs).Methods CoCl2was used in the primary HPAECs to mimize hypoxia-induced cell apoptosis.The aspartate aminotransferase 1(AAT1),and the key enzyme generating endogenous SO2 were over -expressed by transfecting HPAECs with lentivirus containing AAT1 cDNA.HPAECs were divided into 4 groups:vehicle group,vehicle + CoCl2 group,AAT1 group and AAT1 + CoCl2 group.The expressions of AAT1,B-cell lymphoma-2 (bcl-2),bcl-associated X protein (bax),Caspase-3 and activated Caspase-3 (cleaved Caspase-3)in the HPAECs were measured by Western blot.The AAT activity was assessed with colorimetry method.The SO2 content in the HPAECs was in situ observed by SO2-specific fluorescent probe.The HPAECs apoptosis was investigated by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)assay.Results There were significant differences in the endogenous SO2 content,the expre-ssions of AAT1 and bcl-2,and the ratio of cleaved Caspase-3/Caspase-3 among 4 groups of HPAECs were (F＝147.364,23.738,6.521,64.884,all P＜0.05).However,there was no difference in the expression of bax among 4 groups of HPAECs (F＝1.620,P＞0.05).Compared with vehicle group,AAT activity [(0.96 ± 0.24)Carmen's unit/μg vs.(2.21 ± 0. 60)Carmen's unit/μg],endogenous SO2 content (40.71 ± 7.72 vs.105.60 ± 16.20)and bcl-2 expression (0.59 ± 0.19 vs.1.02 ± 0.20)in the HPAECs of vehicle +CoCl2 group were significantly de-creased,while the cell apoptosis assessed by TUNEL and the ratio of cleaved Caspase-3/Caspase-3 (1.56 ± 0.25 vs.0.95 ± 0.13)were significantly increased (all P＜0.05).However,there were no differences in the expression of AAT1 (0. 50 ± 0.12 vs.0.53 ± 0.11)in the HPAECs between vehicle group and vehicle+CoCl2 group (P＞0.05). The SO2 content (351.50 ± 42.43 vs.105.60 ± 16.20)and AAT1 expression (1.22 ± 0.33 vs.0.53 ± 0.11)in the HPAECs of AAT1 group were higher than those of vehicle group (all P ＜0. 05 ). Compared with AAT1 group, endogenous SO2content (333.50 ± 46.22 vs.351.50 ± 42.43)and the expression of AAT1 (1.26 ± 0.36 vs.1.22 ± 0.33)and bcl-2 (1.14 ± 0.38 vs.1.03 ± 0.27)in the HPAECs of AAT1 +CoCl2group did not change (all P＞0. 05).Moreover,no difference was observed in the HPAECs apoptosis assessed by TUNEL and the ratio of cleaved Caspase-3/Caspase-3 (0.51 ± 0.17 vs.0.50 ± 0.11)between the two AAT1 -overexpressed groups (all P ＞0. 05).Conclusion Endo-genous SO2inhibited the hypoxic HPAECs apoptosis stimulated by the treatment of CoCl2.

Objective To evaluate and study percutaneous nephrolithotomy (PCNL) related factors in the treatment of renal calculi caused postoperative fever and its prevention measures. Methods Making a retrospective analysis of the clinical records of 150 patients who underwent PCNL, including age, gender, diabetes history and previous ipsilateral renal surgery, stone type, stone size, whether the complication of upper ureteral stones, preoperative urinary tract infection, hydronephrosis and pyonephrosis, preoperative renal fistula, postoperative centering vein pressure, intraoperative perfusion and the operation time from January 2015 to June 2017. After the operation, the patients were divided into two groups: fever group and non-fever group, and analyzed the related factors of the fever. Results Among the 150 cases, fever occurred in 27 cases after PCNL, taking up 18%. Gender, history of diabetes, staghorn calculi or staghorn stone, stone size, with ureteral calculi, preoperative urine leukocyte count, renal abscess, preoperative renal fistula, postoperative central venous pressure, intraoperative perfusion and operation time between the two groups, the differences that were statistically significant (P < 0.05). Logistic that multivariate analysis showed that female patients with upper ureteral calculi, perfusion, intraoperative volume,preoperative pyonephrosis, long operation time are independent risk factors of fever after operation (OR^>1, P<0.05). Conclusion Routine bacterial culture of urine should be performed before percutaneous nephrolithotomy, urinary tract infection and kidney empyema should be treated thoroughly. The reasonable shorter operative duration and perfusion fluid volume could significantly reduce the incidence of fever after PCNL.

Spinal cord injury (SCI) is a challenging medical problem in the field of neurology, showing high incidence rate, disability rate, treatment cost and low-aged trend. Despite the clinical application of drug intervention, surgical treatment and modern rehabilitation training, no ideal curative effect has been achieved. Therefore, future study is necessary to clarify detailed pathological mechanism of SCI and identify the potential target cells for therapeutic intervention. In the central nervous system (CNS), astrocytes are the most abundant and widely distributed glial cells which play multiple key roles in maintaining homeostasis of the CNS in physiological and pathological conditions. Increasing evidence indicates that astrocytes are ideal therapeutic target cells for SCI. Here, we review current knowledge of the roles of astrocytes in the pathological reaction after SCI, astroglial transplantation and astrocyte reprogramming.

Glial cells, including astrocytes, oligodendrocyte progenitor cells (OPCs), NG2-glia, etc, are broadly distributed throughout the central nervous system (CNS). Also, it has been well known that glial cells play multi-roles in physiological and pathological processes in the CNS, such as maintaining homeostasis, providing neurotrophins for neurons and regulating neural signal transmission. Recently, increasing evidence showed that glial cells may also function as neural stem/progenitor cells and contribute to adult neurogenesis or neuroregeneration. In pathological conditions, for instance, astrocytes and OPCs could be activated to proliferate and differentiate. When cultured in vitro, they could form neurospheres which possess the ability to differentiate into astrocytes, oligodendrocytes and neurons. Additionally, forced expression of exogenous genes in astrocytes and NG2-glia can successfully reprogram them into neurons, which may also be suggestive of their stem/progenitor cell features. Here, we review current knowledge of the stem cell-like properties of glial cells, including what types of glial cells can function as stem/progenitor cells, how they can acquire the stem/progenitor potential and what progenies can be produced. These insights may foster a better understanding of glial cell biology and function in physiological or pathological processes in the CNS and lead to the idea of using the stem/progenitor-like glial cells as endogenous cell source for neural repair.

In order to find highly active antidiabetic agents, the 3-amino group of skeletal structure of thiazolidine-2,4-diones (TZDs) was modified to generate the new molecules TM1 and TM2 in the present research. The new molecules TM3-TM6 containing rhodanine structural units were designed based upon the bioisostere and combination principles. The target molecules TM7, which is similar to the traditional TZDs structurally, were designed by connecting the phenolic hydroxyl of the above target molecules to carbazole through a linker. All of these target compounds were synthesized successfully by selecting suitable synthetic routes with optimized procedures. The assay results of peroxisome proliferator activated receptor response element (PPRE) agonist activity revealed that the PPAR agonist activity was decreased due to the change of TZD ring. The assay of α-glucosidase inhibitory activity and protein tyrosine phosphatase-1B (PTP-1B) inhibitory activity showed that most of the seven serials target molecules have weak activities in vitro. However, 3 of the compounds exhibited strong PTP-1B inhibitory activities. TM2-6 exhibited the highest inhibitory activities, which reached 96.71% with IC₅₀ 1.48 mg·L^-1. In addition, the toxicity prediction disclosed that the highly active compounds were almost non-toxic. These results provide a hint for the development of new antidiabetic

In this study, the inhibitory effect of human umbilical cord-derived mesenchymal stem cells (hUCMSC) on interleukin-17 (IL-17) production in peripheral blood T cells from patients with spondyloarthritis (SpA) were investigated, in order to explore the therapeutic potential of hUCMSC in the SpA. Peripheral blood mononuclear cells (PBMNC) were isolated from patients with SpA (n = 12) and healthy subjects (n = 6). PBMNC were cultured in vitro with hUCMSC or alone. The expression of IL-17 in CD4(+) T cells or γ/δ T cells were determined in each subject group by flow cytometry. IL-17 concentrations in PBMNC culture supernatants were measured by ELISA. The results indicated that the proportion of IL-17-producing CD4(+) T cells and IL-17-producing γ/δ T cells of SpA patients were 4.5 folds and 5 folds of healthy controls [CD3(+)CD4(+)IL-17(+) cells (3.42 ± 0.82)% vs (0.75 ± 0.25)%, P < 0.01; CD3(+)γδTCR(+)IL-17(+) cells (0.30 ± 0.10)% vs (0.06 ± 0.02)%, P < 0.01]. After co-culture of PBMNC in patients with hUCMSC, the increased proportions of CD3(+)CD4(+)IL-17(+) cells and CD3(+)γδTCR(+)IL-17(+) cells in SpA patients were inhibited significantly by hUCMSC [CD3(+)CD4(+)IL-17(+) cells (3.42 ± 0.82)% vs (1.81 ± 0.59)% (P < 0.01); CD3(+)γδTCR(+)IL-17(+) cells (0.30 ± 0.10)% vs (0.16 ± 0.06)% (P < 0.01]. In response to phytohemagglutinin (PHA, 1 µg/ml), PBMNC from SpA patients secreted more IL-17 than that from healthy control [(573.95 ± 171.68) pg/ml vs (115.53 ± 40.41) pg/ml (P < 0.01)]. In the presence of hUCMSC, PBMNC of SpA patients produced less amount of IL-17 [(573.95 ± 171.68) pg/ml vs (443.20 ± 147.94) pg/ml, (P < 0.01)]. It is concluded that the IL-17 production in peripheral blood T cells from SpA patients can be inhibited by hUCMSC, which have therapeutic potential for SpA.
Humans ; Interleukin-17 ; metabolism ; Leukocytes, Mononuclear ; cytology ; Lymphocyte Count ; Mesenchymal Stromal Cells ; Spondylarthritis ; blood ; metabolism ; therapy ; T-Lymphocytes ; metabolism ; Umbilical Cord ; cytology