Neurogenic bladder(NB)is one of the most challenging urinary system disorders,with spinal cord injury(SCI)being an important etiological factor.Animal models provide crucial tools for investigating the pathogenesis,therapeutic strategies,and novel drug screening for NB subsequent to SCI.We reviewed and synthesized recent literature on NB animal models after SCI from both domestic and international sources.This review summarizes and analyzes research advancements using these models in terms of animal species,SCI segments,modeling techniques,and evaluation indicators,with the aim of offering insights and guidance for future experimental research based on animal models of NB following SCI.

Neurogenic bladder(NB)is one of the most challenging urinary system disorders,with spinal cord injury(SCI)being an important etiological factor.Animal models provide crucial tools for investigating the pathogenesis,therapeutic strategies,and novel drug screening for NB subsequent to SCI.We reviewed and synthesized recent literature on NB animal models after SCI from both domestic and international sources.This review summarizes and analyzes research advancements using these models in terms of animal species,SCI segments,modeling techniques,and evaluation indicators,with the aim of offering insights and guidance for future experimental research based on animal models of NB following SCI.

[ Abstract] Objective To explore the role pathway and pattern of the Kruppel-like factor 4 (KLF4) and its mRNA interaction with microRNA (miRNAs) and circular RNA (circRNAs) at 0 hour and the 120 th hour in the rat liver regeneration. Methods The rat 2 / 3 hepatectomy (partial hepatectomy, PH) model was prepared as described by Higgins, the hepatocytes were isolated according to the method of Smedsrod et al, the expression changes of mRNA, miRNA and circRNA together named as competing endogenous RNA (ceRNA) were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3. 2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at the 0 hour and the 120th hour PH, the ratio value of KLF4 mRNA showed 1. 00±0. 16 and 3. 14±0. 27, miR-881-3p displays 18. 30±1. 44 and 0. 47±0. 02, circRNA_20298 indicated 0. 32±0. 10 and 4. 24±0. 22, circRNA_14826 showed 0. 42±0. 13 and 0. 61±0. 08. At the same time, the four kinds of cell apoptosis-related genes adrenoceptor beta 2 (ADRB2), dimethylarginine dimethylaminohydrolase 2 (DDAH2), annexin A5 (ANXA5), ect, which were promoted in expression by KLF4, were down-regulated at 0 hour after PH, but the cell apoptosis-related genes synuclein gamma (SNCG), glutathione-disulfide reductase (GSR), FYVE, RhoGEF and PH domain containing 4 (FGD4), ect, which were inhibited in expression by KLF4, were up-regulated at 0 hour after PH. On the other hand, the cell apoptosis-related genes ANXA5 and thymosin beta 10 (TMSB10), which are promoted in expression by KLF4, were up-regulated at the 120th hour after PH, but the cell apoptosis-related genes chloride intracellular channel 4 (CLIC4) and ataxin 3 (ATXN3), ect, which were inhibited in expression by KLF4, were down-regulated at the 120th hour after PH. Conclusion The correlation in expression and role of the miRNAs, which are inhibited by circRNAs, KLF4, its mRNA is inhibited by miRNAs, and the cell apoptosis-related genes, which are regulated by KLF4, are helpful for the hepatocyte to be in active state 0 hour after PH and to be in apoptotic state 120-hour after PH.

Objective To explore the pathways and patterns which CCAAT/enhancer binding protein β(CEBPβ) mRNA, miR-369-3p and rno-Rmdn2_0006 regulate the hepatocytes in G

Objective:To explore whether CD5 + CD19 + B cells has the function of secreteing interleukin-10 (IL-10) in vitro, and to further investigate its possible effects and mechanisms on CD8 + cells in the process of hepatitis B virus (HBV) infection. Methods:From July 2017 to June 2018, at Wuxi Second People′s Hospital Affiliated to Nanjing Medical University, 23 patients with chronic hepatitis B (chronic hepatitis B group), 18 patients with liver cirrhosis (liver cirrhosis group) and 19 healthy individuals in the same period as healthy controls (healthy control group) were enrolled. Peripheral blood mononuclear cell (PBMC) were isolated and cultured. CD5 + CD19 + B cells were isolated. The cells were analyzed by flow cytometry. The ratio of high CD5 + CD19 + B cells content (>6 % of lymphocytes), the secretion of IL-10 by CD5 + CD19 + B and the ratio of high IL-10 + cells content (>4 % of lymphocytes) of three groups were compared. The effects and possible mechanisms of CD5 + CD19 + B cells on the secreting of interferon-γ (IFN-γ) by CD8 + cells were analyzed. Liver biopsy and immunohistochemistry examination were conducted in 18 patients (13 patients with chronic hepatitis B and 5 patients with liver cirrhosis) and the expression of CD5 + CD19 + B cells in human liver tissues was analyzed. Chi square test and Fisher exact probability test were used for statistical analysis. Results:The ratio of high CD5 + CD19 + B cells content of liver cirrhosis group was higher than that of healthy control group (8/18 vs. 2/19) and the difference was statistically significant (Fisher exact probability test, P=0.029). The precentage of CD5 + CD19 + B cells in healthy control group ( n=10), chronic hepatitis B group ( n=23) and liver cirrhosis group ( n=18) accounted for 81.6%, 82.3% and 70.1%of IL-10 + cells, respectively, and the number of patients with high IL-10 + cells precentage was 2, 7 and 2, respectively. There were no statistically significant differences among three groups (all P>0.05). After stimulated with lipopolysaccharide and cultured for 48 hours, the precentage of CD8 + IFN-γ + cells in lymphocytes of healthy control group ( n=10), chronic hepatitis B group ( n=10) and liver cirrhosis group ( n=10) were compared, and the differences were not statistically significant (all P>0.05). After CD5 + CD19 + B cells were eliminated, the precentage of CD8 + IFN-γ + cells in lymphocytes increased in 5, 4 and 4 patients of healthy control group ( n=10), chronic hepatitis B group ( n=10) and liver cirrhosis group ( n=10). After adding IL-10 receptor blocker, the precentage of CD8 + IFN-γ + cells in lymphocytes in PBMC increased compared with that before the addition of IL-10 receptor blocker (7.23% vs. 6.87%). The results of immunohistochemistry examination of liver biopsy indicated that CD4 + and CD8 + cells were strong expressed in portal area of liver tissue of patients, while CD5 + and CD19 + were less expressed. Conclusions:CD5 + CD19 + B cells do not show obvious quantitative and functional differences in the process of chronic HBV infection, however the ability of CD8 + cells to secrete IFN-γ, which may be achieved by secreting IL-10 rather than by direct contact between cells.

Psoriasis is characterized by abnormal proliferation of keratinocytes, as well as infiltration of immune cells into the dermis and epidermis, causing itchy, scaly and erythematous plaques of skin. The understanding of this chronic inflammatory skin disease remains unclear and all available treatments have their limitations currently. Here, we showed that IMMH002, a novel orally active S1P modulator, desensitized peripheral pathogenic lymphocytes to egress signal from secondary lymphoid organs and thymus. Using different psoriasis animal models, we demonstrated that IMMH002 could significantly relieve skin damage as revealed by PASI score and pathological injure evaluation. Mechanistically, IMMH002 regulated CD3 T lymphocytes re-distribution by inducing lymphocytes' homing, thus decreased T lymphocytes allocation in the peripheral blood and skin but increased in the thymus. Our results suggest that the novel S1P agonist, IMMH002, exert extraordinary capacity to rapidly modulate T lymphocytes distribution, representing a promising drug candidate for psoriasis treatment.

OBJECTIVE: To explore long-term following-up clinical effects of lateral closed high tibial osteotomy for the treatment of knee osteoarthritis. METHODS: Twenty patients with medial unicompartmental knee osteoarthritis were treated with lateral closed high tibial osteotomy and screw fixation from June 2005 to December 2015. Among them, including 17 females and 3 males, aged from 43 to 76 years old with an average of (57.80±8.05) years old. VAS score and KSS score were applied to evaluate recovery degree of pain and function before operation and after operation at 1, 5 and 10 years, and postoperative complications were observed. RESULTS: Sixteen patients were followed-up, the time ranged from 9 to 11(10.0±0.8) years, 4 patients were loss to follow-up. Preoperative VAS score was 7.88±1.15 and decreased to 3.19±0.91, 3.44±0.96, 3.69±1.20 at 1, 5 and 10 years after operation, and there were statistical differences in VAS score between before and after operation at different time points (<0.05). Clinical score of KSS increased from 61.94±5.74 before opertaion to 75.50±4.62, 80.13±3.97, 77.38±6.40 at 1, 5 and 10 years after operation, and there were statistical differences in clinical score of KSS between before and after operation at different time points(<0.05); functional score of KSS increased from 62.81±13.03 before operation to 77.50±8.56, 81.88±6.55, 76.88±10.78, and there were statistical differences in functional score of KSS between before and after operation at different time points(<0.05). All incisions healed well without complications such as fibula nerve injury and fracture nonunion. CONCLUSIONS Lateral closed high tibial osteotomy and screw fixation for knee osteoarthritis could receive good clinical results, stop and delay progress of knee osteoarthritis, and long-term following-up could achieve the same effect as total knee arthroplasty.
Adult ; Aged ; Female ; Follow-Up Studies ; Humans ; Knee Joint ; Male ; Middle Aged ; Osteoarthritis, Knee ; surgery ; Osteotomy ; Tibia ; Treatment Outcome

Spermatozoa are not mature until they transit the epididymis where they acquire motility and the ability to fertilize an egg through sequential modifications. The epididymis has three functional regions, caput, corpus, and cauda, and the luminal proteins of the epididymis play important roles in the above modifications. However, the proteins with differential enrichment between the caput and cauda are still largely unknown. To reveal the functions of the caput and cauda during sperm maturation, luminal proteins from caput and cauda of mice were analyzed by isobaric tag for relative and absolute quantitation (iTRAQ). Overall, 128 differentially enriched proteins were found, of which 46 were caput enriched and 82 were cauda enriched. Bioinformatic analysis showed that lipid metabolism was active in the caput; while anion- and cation-binding activity and phosphorus and organophosphate metabolism were active in the cauda. A new epididymal luminal protein, the caput-enriched PDZ domain containing 1 (Pdzk1), also named Na⁺/H⁺ exchange regulatory cofactor 3 (NHERF3), which plays a critical role in cholesterol metabolism and carnitine transport, was found in the lipid metabolism. Western blotting and immunofluorescence analyses showed that Pdzk1 was expressed in the epididymis but not in the testis, and localized at the middle piece of the sperm tail. Pdzk1 protein level was also reduced in the spermatozoa in case of asthenozoospermic patients compared with that in normozoospermic men, suggesting that Pdzk1 may participate in sperm maturation regulation and may be associated with male infertility. These results may provide new insights into the mechanisms of sperm maturation and male infertility.
Adult ; Animals ; Asthenozoospermia/metabolism* ; Carrier Proteins/metabolism* ; Case-Control Studies ; Epididymis/metabolism* ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism* ; Male ; Membrane Proteins ; Mice ; Sperm Maturation ; Sperm Tail/metabolism* ; Spermatozoa/metabolism* ; Testis/metabolism*

Brain Stem/pathology* ; Death, Sudden/etiology* ; Fatal Outcome ; Humans ; Intracranial Hemorrhages/mortality* ; Leukemia/pathology*

OBJECTIVETo systematically review the safety and efficacy of Qishen Yiqi Dripping Pill (QYDP) as a complementary treatment for chronic heart failure (CHF) patients.

METHODSCNKI, VIP, Wanfang Data, PubMed and Cochrane Library were retrieved for papers on randomized control trials of treating CHF patients by routine western medical treatment plus QYDP. The quality of inclusive literatures was assessed by methods from Cochrane Handbook. Valid data were extracted and analyzed by Meta-analysis using RevMan 5.1.0 Software.

RESULTSTotally 17 trials and 1840 patients in line with standard were included. Results of Meta-analysis showed, compared with the routine Western medical treatment group, additional use of QYDP could decrease re-admission rate [RR = 0.52, 95% CI (0.33, 0.81), P = 0.004] and the mortality rate, improve the clinical efficacy [RR = 1.18, 95% CI (1.12, 1.25), P < 0.01] and cardiac function [RR = 1.18, 95% CI (1.10, 1.27),P < 0.01], increase left ventricular ejection fraction (LVEF) [WMD = 5.57, 95% CI (4.16, 6.97), P < 0.01] of CHF patients. Subgroup analysis of LVEF showed that additional use of QYDP could further improve LVEF [ WMD = 8.34, 95% CI (6.23, 10.45), P < 0.01] of CHF patients and increase the distance of their 6-min walk test [WMD = 94.39, 95% CI (71.89, 116.89), P < 0.01]. But there was no statistical difference in plasma brain natriuretic peptide (BNP) between the two groups. No obvious adverse reaction and liver or kidney damage was reported during the trial.

CONCLUSIONSCompared with the Western medical treatment, additional use of QYDP was safe and could further improve clinical efficacy. However, larger and high-quality clinical trials are necessary for further evidence.