AIM: To explore the effects of fluctuant high blood glucose and stable high blood glucose on apoptosis and the expression of Bax and Bcl-2 in glomerular endothelial cells and renal tubular epithelial cells in diabetic rats. METHODS: 24 SD rats were divided into 3 groups: control group, stable high blood glucose group and fluctuant high blood glucose group. Diabetic rats were induced by intraperitoneal injection of STZ, and the fluctuant high blood glucose animal model was induced by intraperitoneal injection of aspart and glucose at different time points every day. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL), and immunohistochemistry was used to detect apoptosis associated gene bax and bcl-2 expression in kidney. RESULTS: After 4 experimental weeks, a significant increase in cell apoptosis, up-regulation of Bax protein expression in kidney tubular epithelial cell and down-regulation of Bcl-2 in glomerular endothelial cell in fluctuant high blood glucose rats were observed compared with stable high blood glucose rats.CONCLUSION: Fluctuant high blood glucose induces more apoptosis in renal tubular epithelial cells than that in stable high blood glucose diabetic rats.

Objective To explore the effects of oscillating blood glucose on apoptosis in renal tubular epithelial cells of diabetic rats and the role of oxidative stress.Methods Renal tubular epithelial cells (HK-2) were cultured in vitro with stable high glucose or oscillating high glucose,and MTF assay was applied to the neasurement of cell proliferation.Streptozotocin induced diabetic model was established with SD rats and the oscillating high blood glucose animal model was induced by intraperitoneal injection of insulin and glucose at different time points every.day.12 weeks later 24 h urine protein (24hUP),blood urea nitrogen (BUN),serum creatinine (Scr),superoxide dismutase (SOD), and malondialdehyde (MDA)were determined. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL),and immunohisto-chemistry was used to detect apoptosis associated gene Bax,Bcl-2,and NOX-4 expression in kidney.Changes in ultrastructure were observed.Results Oscillating high glucose may inhibit renal cells proliferation obviously when comparing with stable high glucose.In the rats with oscillating blood glucose rather than those with stable high blood glucose,there was a significant increase of BUN,Scr,24hUP,and MDA and a decrease of SOD[ (21.50 ± 1.72 vs 12.50 ± 1.85 )mmol/L,(97.51 ± 7.84 vs 82.12 ± 11.48 ) μmol/L,( 1.57 ± 0.09 vs 1.04 ± 0.12 ) mg/24 h,( 23.50 ± 1.87 vs 14.82 ± 2.96) nmol/ml,( 17.22 ± 1.12 vs 21.11 ± 1.80) U/ml,all P＜0.05 ] ; cell apoptosis was intensified with the up-regulation of Bax and NOX-4 protein expression and down-regulation of Bcl-2 in glomerular endothelial cells; and more severe pathological damages were observed.ConclusionComparing with stable high blood glucose,oscillating high blood glucose induces more apoptosis and less proliferation of renal tubular epithelial cells and the mechanism may be related to the increased oxidative stress.

Objective To explore the psychological stressors of pregnant women with chronic HBV infection.Methods Using phenomenological method of qualitative study,there were 9 pregnant women with chronic HBV infection participated in the study and their mental stress was investigated by deep interview.Results Five main psychological stressors of pregnant women with chronic HBV infection emerged:fear of children being infected; anxious about giving birth in the hospital for infectious diseases; having no idea of selecting the mode of delivery and feeding pattern; worrying about their own health; to feel nervous about playing the role of mothers.Conclusions Healthcare workers should make appropriate health guidance and psychological supports to alleviate the psychological distress combined with features of pregnant women with HBV infection.At the same time,it is necessary to make change of public misunderstanding of hepatitis B,so as to create a fair and friendly social atmosphere for all the hepatitis B patients.

Objective Our retrospective study is aimed to analyze the correlative clinical features of be-tween expressions of miR -135b and miR-141 in colorectal cancer.Methods Clinical data and specimens of patients with colorectal carcinoma at our hospital from 2013 to 2014 were retrospectively collected .The expres-sions of miR-135 b and miR-141 between colon cancer and matched normal colonic tissues were compared .The correlation between the expressions of miR -135 b and miR-141 in colorectal carcinoma and the clinical charac-teristics were discussed .Results A total of 42 patients was retrospective analyzed .The expressions of miR -135b,miR-141 in the colon cancer tissues were obviously higher than that in the normal colonic tissues .The differences of the expression of miR -141 in the colon cancer tissues of different Dukes stages ,degree of differen-tiation,lymph node metastasis and infiltration depth were all significant .The expressions of miR -135 b and miR-141 displayed a positive linear correlation .Conclusion The expressions of miR-135b,miR-141 in colorec-tal cancer are significantly increased ,and the expressions display a remarkable correlation with the Dukes stages , degree of differentiation ,lymph node metastasis and infiltration depth of tumor .The expressions of miR-135 b and miR-141 demonstrate a positive correlation .

The aim of this study was to evaluate the roles of interleukin (IL)-17A in risk stratification and prognosis of patients with sepsis-associated acute kidney injury (SAKI). Methods: We enrolled 146 sepsis patients (84 non-SAKI and 62 SAKI patients) admitted to the emergency department from November 2020 to November 2021. Patients with SAKI were differentiated based on the severity of acute kidney injury. All clinical parameters were evaluated upon admission before administering antibiotic treatment. Inflammatory cytokines were assessed using flow cytometry and the Pylon 3D automated immunoassay system (ET Healthcare). In addition, a receiver operating characteristic (ROC) curve was utilized to determine the prognostic values of IL-17A in SAKI. Results: The levels of creatinine, IL-2, IL-4, IL-6, IL-17A, tumor necrosis factor alpha, C-reactive protein, and procalcitonin (PCT) were significantly higher in the SAKI group than in the non-SAKI group (p < 0.05). The level of IL-17A revealed significant differences among stages 1, 2, and 3 in SAKI patients (p < 0.05). The mean levels of PCT, IL-4, and IL-17A were significantly higher in the non-survival group than in the survival group in SAKI patients (p < 0.05). In addition, the area under the ROC curve of IL-17A was 0.811. Moreover, the IL-17A cutoff for differentiating survivors from non-survivors was 4.7 pg/mL, of which the sensitivity and specificity were 77.4% and 71.0%, respectively. Conclusion: Elevated levels of IL-17A could predict that SAKI patients are significantly prone to worsening kidney injury with higher mortality. The usefulness of IL-17A in treating SAKI requires further research.

Objective:To investigate the clinical effect of lateral rectus abdominis approach combined with presacral decompression for surgical treatment of old Denis type II sacral fractures complicated with upper sacral plexus injury.Methods:A retrospective case series study was performed on the clinical data of 9 patients with old Denis type II sacral fractures complicated with upper sacral plexus injury (L 4-S 1) admitted to Zhongnan Hospital of Wuhan University from June 2010 to December 2016. There were 6 males and 3 females, aged (33.1±7.5)years (range, 15-58 years). Embolization of internal iliac artery and preimplantation of abdominal aortic balloon were performed 2 hours before operation under the guidance of digital subtraction angiography (DSA). Surgery was performed using a single lateral rectus abdominis approach combined with presacral decompression. The operation time, intraoperative blood loss and full weight-bearing time were recorded. The visual analogue scale (VAS) and European QOL Five Dimensional health scale (EQ-5D) were compared before and after operation. The Gibbons' impairment scale was used to assess neurological function. X-ray and CT scan were used to observe internal fixation and fracture healing. The complications during and after operation were recorded. Results:The patients were followed up for 24-52 months [(35.2±5.2)months]. The operation time was (2.9±0.6)hours. The intraoperative bleeding was (573±138)ml, and the full weight-bearing time was (11.6±1.2)weeks. X-ray and CT scan showed bone healing in all patients at the latest follow-up. The VAS and EQ-5D scale improved from preoperative (7.8±0.6)points and (0.34±0.07)points to the final follow-up of (0.8±0.3)points and (0.81±0.05)points ( P<0.05). According to Gibbons classification, 8 patients were grade I and 1 patient was grade II one year after operation ( P<0.01). Namely, the radiation pain of lower extremities was significantly improved in all patients, among which 8 patients showed pain disappeared and completely returned to normal and 1 patient showed residual numbness and hypoesthesia of the affected limbs. No major complications (eg, iatrogenic lumbosacral plexus injury, vital blood vessels or pelvic organs injury) occurred during the operation. During the follow-up period, only one patient developed traumatic hip arthritis and underwent total hip arthroplasty 6 months after operation. Fractures of the remaining patients were healed well without complications like infection, pressure ulcer or implant failure. Conclusions:For old Denis type II sacral fractures complicated with upper sacral plexus injury, lateral rectus abdominis approach combined with presacral decompression can fully decompress the upper sacral plexus nerve, relieve pain, and promote functional rehabilitation, with low incidence of complications. It is an alternative surgical method for the treatment of old Denis type II sacral fractures complicated with upper sacral plexus injury.

Objective:To explore the predictive value of peripheral blood cytokine models on organ functional impairment after chimeric antigen receptor T(CAR-T) cell therapy in children with B-lineage lymphocytic leukemia.Methods:The clinical data of 44 children with acute B-lineage lymphoblastic leukemia who received CAR-T cell therapy at Children′s Hospital of Soochow University from September 2018 to October 2020 were retrospectively analyzed.Peripheral blood cytokines, including interleukin(IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, interferon(IFN)-γ and IL-17A, were measured daily for 14 days after receiving CAR-T cell therapy.The trend of peripheral blood cytokine levels was analyzed at the endpoint of organ function recovery or death within 14 days after CAR-T cell treatment.Receiver operating characteristic curve was used to establish a mathematical prediction model to predict the occurrence of organ damage in the children.Results:Of the 44 children, 31 cases were boys and 13 cases were girls, with a median age of 7.96 (5.19, 11.48)years.Cytokine release syndrome(CRS) response occurred in 95.5% (42/44) children, with 88.1% (37/42) had a grade 1-3 CRS response, and 16.7% (7/42) had a severe grade 4-5 CRS response.Using IL-6>3 892.95 pg/mL as cut-off value, the area under the curve(AUC) for predicting acute respiratory failure was 0.818, with a sensitivity of 0.8 and a specificity of 0.735, while combining IFN-γ>414.4 pg/mL, IL-6>3 892.95 pg/mL and IL-2>27.05 pg/mL were the three cut-off values, with an AUC of 0.741, sensitivity of 0.6 and specificity of 0.912 for predicting acute respiratory failure. Using IFN-γ>1 699.5 pg/mL as cut-off value, the AUC for predicting shock was 0.908, with a sensitivity of 0.722 and a specificity of 1.With IL-6>4 607.3 pg/mL as cut-off value, the AUC for predicting liver injury was 0.964, with a sensitivity of 1 and a specificity of 0.906, while combining both IL-6>4 607.3 pg/mL and IFN-γ>1 446.2 pg/mL as cut-off values, the AUC for predicting liver injury was 0.977, with a sensitivity of 1 and a specificity of 0.906.Combining both IL-6>6 972.2 pg/mL and IFN-γ>3 981.5 pg/mL predicted a positive predictive value of 62.5% and a negative predictive value of 94.4% for grade 4-5 CRS response, with an AUC of 0.846, a predictive sensitivity of 0.714 and a specificity of 0.838, and all children had a combination of two or more organ function injuries.Conclusion:The combination of IL-6 and IFN-γ can effectively predict the incidence of liver injury and cytokine release syndrome.The combination of peripheral blood cytokines IFN-γ, IL-6 and IL-2 can be used to predict the incidence of acute respiratory failure after the treatment of CAR-T cells in children with acute B-lineage lymphoblastic leukaemia.IFN-γ single index can be used to predict the incidence of shock.The combination of IL-6 and IFN-γ can be used to predict the incidence of liver injury and the severity of CRS.

Two Hofmann-Martius-like rearrangement products generated in the production of duloxetine hydrochloride were studied. The structures and generation mechanism of the two Hofmann-Martius rearrangement products were analyzed by LC-MS and NMR. The results showed that under the acidic conditions, the naphthol ether bond of duloxetine would break down and the intermediates of naphthol and the alkyl thiophene cation was generated; the two Hofmann-Martius-like rearrangement products were proven to be a pair of isomers produced by nucleophilic substitution between the naphthol intermediate state and the alkyl thiophene cation intermediate state at the ortho or the para position, respectively. The production of two isomers was related to the strong acidic and protic solvent environment. Therefore, in the salting process of duloxetine hydrochloride, the pH value should be controlled in the range of 3-7 and temperature should be maintained below 50 °C, as well as the nonprotic solvent acetone is chosen to avoid generation of the two isomers.

OBJECTIVES: High fat-induced podocyte injury is one of the important factors leading to obesity related nephropathy (ORG), but the mechanism is not clear. This study aims to explore the mechanism of period circadian clock 3 (PER3) in the oxidative stress and inflammation induced by palmitic acid (PA) in podocytes. METHODS: The C57BL/6J mice were fed with chow and high-fat diet for 16 weeks. The PER3 expression in kidney tissues were detected in the normal body weight group and the obesity group. The PER3 mRNA and protein expression were detected after the podocytes were induced with different concentrations (0, 50, 150 and 300 μmol/L) of PA for 48 h. The PER3 mRNA and protein expression were detected after the podocytes were induced with 150 μmol/L PA for 0, 24, 36, and 48 h. Triglyceride (TG) levels were examined in the PA group, the adenovirus (ad)-PER3+PA group, and the siRNA-PER+PA group after the podocytes were transfected by Ad-PER3 or small interfering RNA (siRNA)-PER3 for 48 h and subsequently were induced with 150 μmol/L PA for 48 h. The differential gene expression was detected using RNA sequencing (RNA-seq) after podocytes were transfected by siRNA-PER3 (siRNA-PER3 group) and siRNA-control (siRNA-control group), respectively. The mRNA levels of nephrin, podocin, podocalyxin, podoplanin, superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPX1), catalase (CAT), and the levels of malondialdehyde (MDA), glutathione (GSH), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and interleukin-2 (IL-2) were detected after podocytes were transfected with Ad-PER3 or Ad-control for 48 h and then they were induced by 150 μmol/L PA for 48 h. RESULTS: The PER3 was down-regulated in the obesity group compared with the normal body weight group ( CONCLUSIONS PER3 can decrease the PA-induced oxidative stress and inflammatory factor secretion via inhibiting the lipogenesis in podocytes.
Animals ; Circadian Clocks ; Mice ; Mice, Inbred C57BL ; Oxidative Stress ; Palmitic Acid/toxicity* ; Podocytes/metabolism*

Objective:To explore the relationship between constitutional types of Chinese medicine and Alzheimer's disease (AD) and to construct an early warning model for AD risk.Methods:In the established multimodal interventions to delay dementia and disability in rural China (MIND-China) study, 4 033 elderly subjects aged ≥60 years old were included. The data including demographic, underlying disease and neuropsychological data were collected.The Chinese medicine service record form for the elderly was used to assess constitutional types of Chinese medicine and to apply the NIA-AA diagnostic criteria published by the National Institute on Aging and the Alzheimer's Association in 2011 for the diagnosis of clinically likely AD. Logistic regression analysis and AD risk prediction models were constructed using R statistical software, and the final prediction results were presented using columnar plots.Results:The MIND-China cohort was dominated by the abnormal constitution (69.28%), of which Phlegm-wetness type was the most common (58.05%), followed by Yang-deficiency type (23.85%). The most constitutional type of Chinese medicine among AD patients was Phlegm-wetness type (54.35%), followed by Qi-depression type (38.04%). Multi-factorial logistic regression analysis suggested that increasing age ( β=0.101, P<0.001, OR=1.107, 95% CI=1.069-1.146) and Qi-depression type ( β=0.622, P=0.016, OR=1.862, 95% CI=1.116-3.076) were able to increase the risk of developing AD, while education ( β=-1.047, P<0.001, OR=0.351, 95% CI=0.205-0.584) was able to reduce the risk of developing AD. By using the risk score model to calculate the total risk score for each subject and plotting the receiver operating characteristic curve (ROC), the area under the ROC was 0.769 and the calibration curve showed excellent consistency between prediction and reality. Conclusion:Older adults with Qi-depression type are significantly associated with an increased likelihood of AD.