The aim of this investigation was to determine the optimal storage medium for testicular hypothermic transportation and identify the ideal concentration for the application of the protective agent 5-aminolevulinic acid (5-ALA). Furthermore, this study aimed to explore the underlying mechanism of the protective effects of 5-ALA. First, we collected and stored mouse testicular fragments in different media, including Hank's balanced salt solution (HBSS; n = 5), Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 (DMEM/F12; n = 5), and alpha-minimum essential medium (αMEM; n = 5). Storage of testicular tissue in HBSS preserved the integrity of testicular morphology better than that in the DMEM/F12 group ( P < 0.05) and the αMEM group ( P < 0.01). Testicular fragments were subsequently placed in HBSS with various concentrations of 5-ALA (0 [control], 1 mmol l -1 , 2 mmol l -1 , and 5 mmol l -1 ) to determine the most effective concentration of 5-ALA. The 2 mmol l -1 5-ALA group ( n = 3) presented the highest positive rate of spermatogonial stem cells compared with those in the control, 1 mmol l -1 , and 5 mmol l -1 5-ALA groups. Finally, the tissue fragments were preserved in HBSS with control ( n = 3) and 2 mmol l -1 5-ALA ( n = 3) under low-temperature conditions. A comparative analysis was performed against fresh testes ( n = 3) to elucidate the underlying mechanism of 5-ALA. Gene set enrichment analysis (GSEA) for WikiPathways revealed that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was downregulated in the 2 mmol l -1 5-ALA group compared with that in the control group (normalized enrichment score [NES] = -1.57, false discovery rate [FDR] = 0.229, and P = 0.019). In conclusion, these data suggest that using 2 mmol l -1 5-ALA in HBSS effectively protected the viability of spermatogonial stem cells upon hypothermic transportation.
Male ; Animals ; Testis/cytology* ; Aminolevulinic Acid/pharmacology* ; Mice ; Organ Preservation/methods* ; Organ Preservation Solutions/pharmacology* ; Cryopreservation/methods*

The maintenance of hematopoietic stem cells (HSCs) is a complex process involving numerous cell-extrinsic and -intrinsic regulators. The first member of the cyclin-dependent kinase family of inhibitors to be identified, p21, has been reported to perform a wide range of critical biological functions, including cell cycle regulation, transcription, differentiation, and so on. Given the previous inconsistent results regarding the functions of p21 in HSCs in a p21-knockout mouse model, we employed p21-tdTomato (tdT) mice to further elucidate its role in HSCs during homeostasis. The results showed that p21-tdT+ HSCs exhibited increased self-renewal capacity compared to p21-tdT- HSCs. Zbtb18, a transcriptional repressor, was upregulated in p21-tdT+ HSCs, and its knockdown significantly impaired the reconstitution capability of HSCs. Furthermore, p21 interacted with ZBTB18 to co-repress the expression of cKit in HSCs and thus regulated the self-renewal of HSCs. Our data provide novel insights into the physiological role and mechanisms of p21 in HSCs during homeostasis independent of its conventional role as a cell cycle inhibitor.
Animals ; Hematopoietic Stem Cells/cytology* ; Cyclin-Dependent Kinase Inhibitor p21/genetics* ; Mice ; Cell Self Renewal ; Repressor Proteins/genetics* ; Mice, Inbred C57BL ; Mice, Knockout ; Humans ; Gene Expression Regulation

Objective: Schizophrenia is a complex and devastating psychiatric disorder with a strong genetic background. However, much uncertainty still exists about the role of genetic susceptibility in the pathophysiology of schizophrenia. TEA domain transcription factor 1 (TEAD1) is a transcription factor associated with neurodevelopment and has modulating effects on various nervous system diseases. In the current study, we performed a case–control association study in a Northeast Chinese Han population to explore the characteristics of pathogenic TEAD1 polymorphisms and potential association with schizophrenia. Methods: We recruited a total of 721 schizophrenia patients and 1,195 healthy controls in this study. The 9 single nucleotide polymorphisms (SNPs) in the gene region of TEAD1 were selected and genotyped. Results: The genetic association analyses showed that five SNPs (rs12289262, rs6485989, rs4415740, rs7113256, and rs1866709) were significantly different between schizophrenia patients and healthy controls in allele or/and genotype frequencies. After Bonferroni correction, the association of three SNPs (rs4415740, rs7113256, and rs1866709) with schizophrenia were still evident. Haplotype analysis revealed that two strong linkage disequilibrium blocks (rs6485989-rs4415740-rs7113256 and rs16911710-rs12364619-rs1866709) were globally associated with schizophrenia. Four haplotypes (C-C-C and T-T-T, rs6485989-rs4415740-rs7113256; G-T-A and G-T-G, rs16911710-rs12364619-rs1866709) were significantly different between schizophrenia patients and healthy controls. Conclusion The current findings indicated that the human TEAD1 gene has a genetic association with schizophrenia in the Chinese Han population and may act as a susceptibility gene for schizophrenia.

OBJECTIVE: To explore the relationship between drug treatment and outcomes in patients with late-onset severe pneumonia (LOSP) after allogeneic stem cell transplantation (allo-SCT). METHODS: We retrospectively analyzed the effects of the initiation time of treatment drugs, especially antiviral drugs and glucocorticoids on the clinical outcomes in 82 patients between January 2016 and August 2021 who developed LOSP after allo-SCT in Peking University People's Hospital. Univariate analysis was performed by Mann-Whitney U test and χ² test, and multivariate analysis was performed by Logistic regression. When multiple groups (n>2) were involved in the χ² test, Bonferroni correction was used for the level of significance test. RESULTS: Of all 82 patients in this study, the median onset time of LOSP was 220 d (93-813 d) after transplantation, and the 60-day survival rate was 58.5% (48/82). The median improvement time of the survival patients was 18 d (7-44 d), while the median death time of the died patients was 22 d (2-53 d). Multivariate analysis showed that the initiation time of antiviral drugs from the onset of LOSP (< 10 d vs. ≥10 d, P=0.012), and the initiation time of glucocorticoids from antiviral drugs (< 10 d vs. ≥10 d, P=0.027) were the factors affecting the final outcome of the patients with LOSP at the end of 60 d. According to the above results, LOSP patients were divided into four subgroups: group A (antiviral drugs < 10 d, glucocorticoids ≥10 d), group B (antiviral drugs < 10 d, glucocorticoids < 10 d), group C (antiviral drugs ≥10 d, glucocorticoids ≥10 d) and group D (antiviral drugs ≥10 d, glucocorticoids < 10 d), the 60-day survival rates were 91.7%, 56.8%, 50.0% and 21.4%, respectively. CONCLUSION Our study demonstrated that in patients who developed LOSP after allo-SCT, the initiation time of antiviral drugs and glucocorticoids were associated with the prognosis of LOSP, and the survival rate was highest in patients who received antiviral drugs early and glucocorticoids later. It suggested that for patients with LOSP of unknown etiology should be highly suspicious of the possibility of a secondary hyperimmune response to viral infection.
Antiviral Agents/therapeutic use* ; Glucocorticoids/therapeutic use* ; Hematopoietic Stem Cell Transplantation/methods* ; Humans ; Pneumonia/etiology* ; Prognosis ; Retrospective Studies ; Transplantation, Homologous/adverse effects*

OBJECTIVE: To understand the current state and problem of screening and management of chronic kidney disease (CKD) in the community, and to explore the improving strategies. METHODS: We established a community-CKD integrated data science platform based on medical information from 79 community health centers, in Xicheng District, Beijing. Patients who referred to 79 community health centers from 21 June 2015 to 20 November 2021 were retrospectively included in this study using the CKD data platform. The monitoring of the indicator of kidney injury, risk factor control, medicine use and device configuration in community were assessed in the study. RESULTS: In the study, 70.6% of the population were identified with high risk of CKD in the total 374 498 individuals who referred to the community health centers. Hypertension (62.3%), coronary heart disease (43.3%) and diabetes (30.4%) were the most common risk factors in high-risk CKD population. Only 17.2% of the patients with high risk of CKD were screened for kidney injury including at least one serum creatine (Scr) or albuminuria test, among which 10 992 (24.2%) individuals were defined as CKD. 22.7% (11 338/49 908) of the total patients with kidney screening in community were defined as CKD, of whom, 42.6% and 46.1% were identified by estimated glomerular filtration rate (eGFR) < 60 mL/(min·1.73 m²) and abnormalities of urinary proteins, respectively. The overall CKD detection rate in the community was 5.2% (19 299/374 498), and the miss-diagnosis rate of CKD was 38.1%. Of the 79 community health centers, 13 (16.5%) were equipped with ACR testing device, and eGFR was reported directly in 66 (83.5%) centers. Altogether 60.3% and 99.7% of the community CKD patients achieved glucose control and blood pressure control, respectively, and 59.3% of the CKD patients who had proteinuria was treated with renin-angiotensin-aldosterone system (RAAS) inhibitors. CONCLUSION High-risk CKD population account for a substantial proportion of patients who refer to the community. Early screening, prevention and management of CKD in the community are of great importance to improve the prognosis and decrease the burden of CKD. It's essential to establish a screening and monitoring system, strengthen standardized management and clinician training for improving the ability of CKD management in the community.
Albuminuria/epidemiology* ; Blood Glucose ; Creatine ; Glomerular Filtration Rate ; Humans ; Renal Insufficiency, Chronic/therapy* ; Retrospective Studies

OBJECTIVE: To study the effect of Tai Chi (TC) and resistance training (RT) with different intensity on the cancer-related fatigue (CRF) and quality of life (QoL) of middle-aged and elderly cancer patients. METHODS: Totally 120 cancer patients were enrolled and randomly assigned to 4 groups by a random number table, including TC group, high-intensity 60% one repetition maximum (1-RM) RT group (HIRT), low-intensity (30% 1-RM) RT group (LIRT) and control group, 30 patients in each group. Participants in the TC group received 24-form simplified Yang-style TC training at a frequency of 40 min per day, 3 days per week for 12 weeks. Patients in the two RT groups received 10 sessions, 6 designated movements per day, 3 days per week for 12 weeks. The 1-RM of 6 muscle groups, fat mass (FM), lean body mass (LBM), along with the scores of Brief Fatigue Inventory (BFI), QoL questionnaire for Chinese cancer patients receiving chemobiotherapy (QLQ-CCC), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9) and Pittsburgh Sleep Quality Index (PSQI) were measured before and after training. The adverse effect was also observed. RESULTS: After 12-week intervention, patients in both TC and RT groups showed significant improvements in CRF and QLQ-CCC compared to pre-treatment (P<0.05). Compared with the LIRT and TC groups, patients in the HIRT group improved more significantly in increasing muscle strength and LBM, and reducing in FM (P<0.05). Patients in the TC group significantly increased in lower limb muscle strength compared with the LIRT group (P<0.05). In addition, patients in the TC group showed more significant improvements in scores of GAD-7, PHQ-9 and PSQI than 2 RT groups (P<0.05). CONCLUSIONS TC and RT, both low- and high-intensity training, can significantly increase muscle strength, reduce CRF and improve QoL in the middle-aged and elderly cancer patients. TC has a better effect than RT in terms of sleep quality and mental health. The long-term application is needed to substantiate the effect of TC as an alternative exercise in cancer patients.

ObjectiveNecrotizing fasciitis (NF) has a high rate of deterioration and rapid progress, and the mortality rate is still high even after receiving treatment. The study was to explore evaluation value of serum procalcitonin (PCT), C-reactive protein (CRP) and plasma albumin (ALB) and prealbumin (PA) in the prognosis of patients with perianal necrotizing fasciitis (NF).MethodsAll data and detection data of serum PCT, CRP and plasma ALB, PA at admission from 41 perianal NF patients admitted to Hefei first people's Hospital Group from May 2009 to August 2019 were retrospectively collected. The death status was statistically analyzed. The patients in this group were divided into survival group and non-survival group, and the predictive value of various indicators on the prognosis of NF was evaluated. ResultsThe ratio of male to female was 9.25∶1. There were multiple complications, and diabetes mellitus was most common (41.46%). The patients with mixed infection and negative bacterial culture accounted for 12.20% and 17.07%, respectively. There were many kinds of bacteria detected out. Klebsiella pneumoniae (20.45%), Escherichia coli (15.91%) and streptococcus (15.91%) were common. All underwent one or more surgical treatments, with mortality of 17.07%. There was no significant difference between survival group and death group in gender, complications, microbiological test results, operation status within 6h or and nutrition support (P>0.05), while there were significant differences in time from onset to admission, proportion of patients in ICU, serum PCT and CRP, plasma ALB and PA and proportion of patients undergoing vacuum sealing drainage (VSD) (P<0.05). Logistic multivariate regression analysis showed that long duration from onset to admission, staying in ICU, high serum PCT and CRP, low plasma ALB and PA, and no conducting VSD were risk factors of poor prognosis (P<0.05). Serum PCT, CRP and plasma ALB, PA predict the prognosis receiver operating characteristic(ROC) curve, the area under the curve is 0.859, 0.811, 0.802, 0.747; the area under the curve of the four indicators combined prediction is 0.926.ConclusionThere are certain features in terms of gender, complications and microorganisms in perianal NF patients. Death risk is high. In addition, serum PCT and CRP, plasma ALB and PA are also related with prognosis, which can be applied as biochemical indexes for prognosis evaluation.

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*

Objective The aim is to analyze the spatial-temporal correlation of dysentery incidence in 31 provinces, municipalities and autonomous regions in China from 2004 to 2016, and to predict the short-term incidence of dysentery in China. Methods Data about the incidence of dysentery from 2004 to 2016 was collected. Arcgis and Geoda were used to create visualized grading maps and analyze spatial correlation. The auto-regressive integrated moving average model (ARIMA)was used to predict the incidence of dysentery in 2017 and evaluate the prediction accuracy of the model. Results The incidence of dysentery in China declined with each passing year from 2004 to 2016. The incidence of dysentery in the western region was significantly higher than the eastern region, except high incidence rate in Beijing and Tianjin. There was no significantly global correlation in the incidence rate, but there was local aggregation. Qinghai had turned from high-level aggregation to low-level accumulation. Inner Mongolia and Shanxi had changed from no local aggregation to low-high accumulation. Shaanxi has long been high-high, and the southeast coastal areas had been low-low accumulation for a long time. The optimal model ARIMA (1,0,0) (2,1,1)12 was established to predict the incidence of dysentery, and the prediction results were roughly consistent with the observations. Conclusion The incidence of dysentery from 2004 to 2016 is not spatially mobile but clustered. The incidence of dysentery in Beijing, Tianjin, Shaanxi and most of the western regions is severe. The ARIMA model is suitable for forecasting the incidence of short-term dysentery. And our analysis may help prevent and control the incidence of dysentery in China.

Two new polyketides, chinoketides A and B (1 – 2) with a known compound xylarphthalide A (3), were isolated from the solid medium of the endophytes from the leaves of the relic plant Distylium chinense with the “black-box” co-culture method, and the structures of two new compounds were elucidated by NMR, MS and CD spectra. And the absolute configurations of chinoketides A (1) and B (2) were determined as 2R,3R,8S and 5R,6S by calculating their ECD spectra to compare with the experimental CD spectra. Finally, the antimicrobial activities were evaluated to Erwinia carotovora sub sp. Carotovora (Jones) Bersey et al, and the results showed that compounds 1 – 3 displayed the antimicrobial activities with MIC value at 20.5, 30.4 and 10.2 µg/mL.
Coculture Techniques ; Endophytes ; Methods ; Pectobacterium carotovorum ; Plants ; Polyketides