Objective: To elucidate the role of A39S mutation of DJ-1 in the onset of Parkinson’s disease (PD) and identify genes for which expressions are abnormally regulated by A39S DJ-1 mutation. Methods: We established HEK293 cell lines which stably expressed empty vector, wild-type DJ-1 and A39S mutated DJ-1 respectively. DNA microarrays were used to identify genes for which expressions change in wild-type DJ-1 cells and A39S DJ-1 mutant cells. Results: Compared with the cell line expression empty vector, we identified 42 differentially regulated genes (including 14 up-regulated genes and 28 down-regulated genes) in the wild-type DJ-1 cells and 8 differentially regulated genes (including 6 up-regulated genes and 2 down-regulated genes) in the A39S DJ-1 mutant cells. Compared with the wild-type DJ-1 cells, only the expression of UGT2B7 gene was down-regulated in A39S DJ-1 mutant cells. hTese differentially regulated genes were mainly related to signal transduction, regulation of transcription, apoptosis and metabolism. Conclusion: A39S mutated DJ-1 may disturb the transcriptional activities of DJ-l and involve in the pathogenesis of PD.

OBJECTIVE To investigate the protective effects and mechanism of diterpene ginkgolides meglumine injection (DGMI) against oxidative stress induced by oxygen-glucose deprivation (OGD) in SH-SY5Y cells. METHODS SH-SY5Y cells were divided into five groups: normal control, model control (OGD group) and drug(25 mg · L- 1) administration groups including DGMI group, extract of ginkgo biloba leaves injection group (EGBLI) and lactones ginkgo biloba injection group (LGBI). The cells suffered from oxygen-glucose deprivation (OGD) for 4 h, followed by reoxygenation with drugs for 6 h. Then, cell viabilities were detect using CCK-8 assays, reactive oxygen species (ROS) levels using fluorescence probe DCFH-DA and superoxide dismutase (SOD) activities using WST-1 test. Western blotting was used to detected protein levels of hemeoxygenase-1(HO-1), NAD(P)H, quinone oxidore?ductase l (Nqo1), protein kinase B (Akt), phosphorylated Akt (p-Akt), nuclear factor-E2-related factor2 (Nrf2) and phosphorylated Nrf2 (p-Nrf2). The cells were induced by OGD for 4 h, followed by reoxygen?ation and DGMI for 1 h, combined with different concentrations of PI3K inhibitor (LY294002) (at the final concentration of 12.5, 25 and 50 μmol · L-1) before the protein levels of AKT, p-AKT, Nrf2 and p-Nrf2 were detected by Western blotting. RESULTS SH-SY5Y cells induced by OGD for 4 h resulted in an increase in ROS(P<0.01), but a decrease in cell viabilities(P<0.01), SOD activities(P<0.01), and antioxidant protein levels ( Akt, p-Akt, Nrf2, p-Nrf2, HO-1 and Nqo1) (P<0.01). Compared with OGD group, treatment with reoxygenation and drugs (DGMI,EGBLI and LGBI respectively) for 6 h resulted in a decrease in ROS (P<0.01), but an increase in cell viabilities, SOD activities and antioxidant protein levels of p-Nrf2, HO-1, Nqo1 and p-Akt(P<0.05,P<0.01). DGMI group showed the best efficiently. Moreover, after OGD for 4 h, compared with DGMI group, combining reoxygenation and DGMI with LY294002 for 1 h resulted in a concentration-dependent inhibition of the protein levels of p-AKT and p-Nrf2(P<0.01). CONCLUSION DGMI 25 mg · L-1 can inhibit oxidative stress in SH-SY5Y cells induced by OGD by increasing the activity and expression of Nrf2 through PI3K/Akt pathway, which may be one of the mechanisms by which DGMI protects neurons from stroke.

Objective To review the current research and application of root cause analysis (RCA) method in China's hospital management.Methods A retrospective analysis in six aspects was made by means of formulating a retrieval strategy and inclusion criteria, retrieval of databases, and literature review.Results The number of Chinese RCA researches was increasing year by year, mostly from researcher of the eastern coastal areas.These studies focused on the effects of RCA application outcomes and nursing safety.Tools in use were mainly fishbone diagram, brainstorming and 3-why method.72.24% of the root causes as found in literature were system factors, and 27.76% were human factors.Most of the researches made positive comments on RCA.Conclusions RCA is being warmly embraced by China's hospital management as it can positively change the accountability culture towards adverse events.Yet RCA has not been satisfactorily applied, and its future research and application in China's hospital management need more in-depth study and critical analysis.

This study was aimed to explore the suppression of nitric oxide (NO) production in RAW264.7 cells by total lactones fraction from Andrographis paniculata. The inflammatory model in vitro was established by stimulating the RAW264.7 cells with lipopolysaccharide (LPS). The NO production and inhibitory rate were determined by Griess assay. Cytotoxicity was evaluated by MTT method. The results showed that total lactones fraction ofA. paniculata suppressed NO production in a concentration-dependent manner in the concentration range from 5 to 50μmol·L-1 and their IC50 values were 8.58μmol·L-1, 11.52μmol·L-1 and 8.94μmol·L-1, respectively. In this condition, major constituents were andrographolide (5-60μmol·L-1), dehydroandrographolide (5-100μmol·L-1) and neoandrographolide (5-100μmol·L-1) inhibited NO production in a dose-dependent manner with an IC50 values of 17.54μmol·L-1, 49.54μmol·L-1 and 41.80μmol·L-1, respectively. It was concluded that the NO inhibitory activity of total lactones fromA. paniculata was better than three active ingredients, which may be able to provide a theoretical foundation and scientific basis for the preparation and clinical application of total lactones fraction fromA. paniculata.

Objective To investigate clinical and genetic characteristics of Chinese patients with hereditary spastic paraplegia (HSP).Methods To perform retrospective analyses of clinical data from 179 HSP Han Chinese patients from Xiangya Hospital and National Laboratory of Medical Genetics of China.Results The 179 patients comprised of 114 familial cases (from 41 families with AD inheritance and 37 families with AR inheritance ) and 65 sporadic cases.Genetic anticipation was not found, and nonpenetrance was observed in some HSP families.Male to female ratio was 1.84 to 1.The mean age of onset was ( 18.1 ± 14.0) years, and the mcan duration of disease was ( 12.3 ± 11.5) years.AD-HSP patients had an older age of onset ( ( 19.7 ± 14.0) years) and a longer duration ( ( 17.9 ± 14.4) years) than ARHSP patients (t =2.196 and 4.404, P value were less than 0.05 and 0.01 respectively).Most AD patients manifested as "pure" form, while "complicated" form occurred more frequently in AR patients (F =19.322, P ＜ 0.01 ).Leg stiffness and clumsiness were often the early symptoms at the beginning of the disease, and the most common leg signs were hypertonia, hyperreflexia and pathological reflexes.Other signs included ankle clonus (46.9% ), weakness (42.5% ) and deformities (30.7% ).Ataxia, dysarthria,mental retardation, and foot deformity were more frequently seen in AR-HSP patients than AD-HSP patients,but the frequency of urinary symptoms was higher in AD-HSP patients.Among 65 patients with MRI examination of the head, 13 cases and 9 cases showed corpus callosal dysplasia and cerebellar atrophy,respectively.In addition, spinal cord atrophy was found in 7 of 45 patients undergone MRI examination of the spine.Conclusions Adolescent onset of HSP is common, and more males than females are affected.When compared with AR-HSP, AD-HSP patients have an older age of onset, a longer duration, and more marked urinary symptoms.Most AD-HSP cases are of "pure" form, while most AR-HSP cases manifest as "complicated" form with ataxia, dysarthria, and mental retardation.Dysplasia of corpus callosum is commonly seen in AR-HSP individuals than AD-HSP.HSP manifest gender-related clinical heterogeneity,illustrating the phenomenon of "female protection".

ObjectiveTo assess the effectiveness of tele-medicine and self-management goal(SMG) setting technique used in the diabetes management in the community setting.Methods It is a control-group study.415 type 2 diabetic residents were recruited from the Shanghai Wuliqiao community based on existing medical records.The subjects were divided into two groups,the study group was cared by general practitioners (GPs) specialists cooperation through the tele-medicine mechanism,the other was a control group.For the study group,a cooperation pathway between community health care centers and general hospitals were established.Standardized training and guidelines were provided to community health workers,regarding the setting of management goals of blood glucose and blood pressure,treatment plan,patient education,and SMG techniques.Fasting blood glucose ( FBG ) and 2 h postprandial blood glucose (2hBG) in the study group were monitored,followed by community health workers visiting monthly with seminars for diabetes education.At the baseline and the 12tb month,FBG,2hBG,HbA1C,blood pressure,triglyceride,total cholesterol,body mass index,waist-hip ratio were determined in each group.A survey was conducted to evaluate the costs of diabetes treatments,the knowledge base related to their disease,lifestyle,and the awareness of the new care model.The rates of achieving the goal of blood glucose,blood pressure,and HbA1Ccontrol were calculated.Internet case discussion between GPs-Specialists and referral to certain specialists were implemented when some patients did not reach the control goal.ResultsBy the 12 month follow up,FBG,2hBG,HbAIc,blood pressure of the study group were lower than the baseline,and as well as the control group with statical significance (P＜0.05).There are other improvcments:diabetes knowledge (29.1％ vs 5.5％ ),healthy diet (9.6％ vs -10.4％ ),blood glucose monitoring (30.3％ vs 10.8％ ),support for diabetes care in community (35.7％ vs 9.4％ ),and the preference of the new model (63.8％ vs 17.9％ ) with statistical significauce (P＜0.01 ).As for the medical costs,the study group's monthly costs were consistently lower than the control's.( -3.39Yuan vs 32.26 Yuan,P＜0.05).ConclusionsThe new diabetes care model based on GPs-Specialists tele-medicine and SMG in community opens the door to the community based care model formulation in regard to the health quality and costs control.The deployment of more technologies and management techniques could be explored further to improve the outcomes of community based chronic disease care model.

Objective:To observe the clinical efficacy of Dachengqi decoction combined with octreotide in the treatment of patients with acute pancreatitis (AP).Methods:From March 2018 to February 2021, a total of 68 patients with mild acute pancreatitis (MAP) and moderately severe acute pancreatitis (MSAP) admitted to Shanghai Traditional Chinese Medicine-Integrated Hospital were included, and they were randomly divided into western medicine treatment group and Dachengqi decoction group. The patients in the western medicine treatment group received conventional western medicine (octreotide+symptomatic treatment); in the Dachengqi decoction group, 100 mL of Dachengqi decoction was taken orally on the basis of conventional western medicine, twice a day; the observation time for both groups was 7 days. The levels of inflammation parameters [white blood cell count (WBC), interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP)] and serum amylase (Amy) before and after treatment of patients between the two groups, as well as the occurrence of clinical efficacy indicators and adverse reactions were compared.Results:Among the 68 included patients, 4 were excluded because the specimen was not obtained or the patient gave up the treatment. A total of 64 patients were finally enrolled in the analysis, including 32 cases in the Dachengqi decoction group and 32 cases in the western medicine treatment group respectively. There was no statistically significant difference in inflammation parameters or serum Amy levels before treatment between the two groups. At 7 days of treatment, the inflammatory parameters and serum Amy levels of the two groups were significantly lower than those before treatment [western medicine treatment group: WBC (×10 9/L) was 5.94±2.08 vs. 11.81±3.66, IL-6 (ng/L) was 7.22 (5.72, 14.23) vs. 30.13 (15.77, 85.37), PCT (μg/L) was 0.068 (0.052, 0.128) vs. 0.290 (0.231, 0.428), CRP (mg/L) was 26.0 (18.3, 35.8) vs. 112.0 (62.0, 126.0), Amy (U/L) was 77 (57, 116) vs. 352 (162, 1 576); Dachengqi decoction group: WBC (×10 9/L) was 5.56±2.04 vs. 12.22±2.85, IL-6 (ng/L) was 5.70 (3.26, 11.06) was 50.30 (23.99, 88.32), PCT (μg/L) was 0.038 (0.028, 0.808) vs. 0.308 (0.129, 0.462), CRP (mg/L) was 11.0 (3.5, 24.0) vs. 150.0 (75.0. 193.0), Amy (U/L) was 78 (57, 104) vs. 447 (336, 718); all P < 0.05], and the levels of IL-6, PCT, and CRP decreased more significantly after treatment in the Dachengqi decoction group (all P < 0.05). The total clinical effective rate of patients in the Dachengqi decoction group was significantly higher than that of the western medicine treatment group [93.75% (30/32) vs. 71.88% (23/32), P < 0.05]. There was no obvious adverse event during the treatment and observation period in the two groups. Conclusion:Dachengqi decoction combined with octreotide therapy could improve the clinical efficacy of AP patients, and its mechanism might be related to reducing the level of inflammatory factors, thereby inhibiting the inflammatory response, and regulating the level of serum Amy.

Objective:To explore the therapeutic effect and mechanism of Dachengqi decoction on patients with mild acute pancreatitis (MAP).Methods:A parallel randomized controlled trial was conducted. Sixty-eight patients with acute pancreatitis (AP) admitted to Shanghai Traditional Chinese Medicine (TCM)-Integrated Hospital from March 2018 to February 2021 were enrolled. Referring to the condition on admission of the patients and whether they agreed to receive the Dachengqi decoction or not, they were divided into conventional treatment group and Dachengqi decoction group according to the principle of 1∶1 equal randomness. Meanwhile, 20 healthy volunteers were recruited as controls. Both groups of patients were treated with octreotide, fasting, gastrointestinal decompression, antipyretic and analgesic, anti-inflammatory, inhibition of gastric acid and pancreatic juice secretion, maintenance of electrolyte balance and other western conventional medicine. The patients in the Dachengqi decoction group received Dachengqi decoction orally on the basis of routine treatment, 100 mL each time, twice a day, for seven consecutive days. The inflammation parameters [white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6)] before and after treatment and the recovery time of gastrointestinal function (first exhaust time, time to recover bowel sounds, first defecation time) of patients were recorded. 16S rRNA gene sequencing of stool samples was recorded, and normalized data were obtained after quality control and other related processing. The data were subjected to diversity analysis (Alpha diversity and Beta diversity) and linear discriminant analysis effect size analysis (LEfSe analysis) to observe changes in the gut microbiota of MAP patients. Spearman rank correlation coefficient was used to analyze the correlation between inflammatory indexes and microorganisms at the intestinal genus level. Blood, urine, stool samples, renal function, and electrocardiogram (ECG) during treatment of MAP patients were detected to assess the safety of the treatment.Results:Of the 68 patients with AP, 16 were excluded from moderate-severe AP, 4 were not collected or voluntarily abandoned treatment. Finally, 48 patients with MAP were enrolled, 24 in the conventional treatment group and 24 in the Dachengqi decoction group. The inflammation parameters levels at 7 days of treatment in both groups were significantly lower than those before treatment. CRP, PCT and IL-6 levels in the Dachengqi decoction group were significantly lower than those in the conventional treatment group [CRP (mg/L): 8.50 (3.50, 13.00) vs. 16.00 (9.25, 29.75), PCT (μg/L): 0.06 (0.03, 0.08) vs. 0.09 (0.05, 0.11), IL-6 (ng/L): 6.36 (3.96, 10.79) vs. 13.24 (6.69, 18.87), all P < 0.05]. The first exhaust time, time to recover bowel sounds and first defecation time in the Dachengqi decoction group were significantly shorter than those in the conventional treatment group [first exhaust time (days): 1.62±0.65 vs. 2.80±0.65, time to recover bowel sounds (days): 1.13±0.58 vs. 2.31±0.76, first defecation time (days): 3.12±0.75 vs. 4.39±0.76, all P < 0.05]. The analysis of intestinal microflora diversity showed that both the diversity and abundance of microbial communities were the highest in the healthy control group and the lowest in the conventional treatment group. In addition, the coincidence degree of microbial communities in healthy controls and MAP patients was small, while the coincidence degree of MAP patients among different treatment methods was relatively large. LEfSe analysis showed that Dachengqi decoction reduced the relative abundance of Escherichia coli-Shigella and Clostridium erysipelae, and increased the relative abundance of three beneficial bacteria, namely Lactobacillus, Rombutzia and Brutella. In the intestines of MAP patients, Lactobacillus mucilaginus and Lactobacillus conjunctus were significantly enriched. Correlation analysis showed that positive correlations between Escherichia coli- Shigella and the four inflammatory indicators including WBC, CRP, PCT, IL-6 were statistically significant ( r value was 0.31, 0.41, 0.57, 0.43, respectively, all P < 0.05). There was no significant correlation between other bacteria and inflammatory indicators. During the treatment, there was no obvious abnormality in blood, urine and feces, renal function and ECG of MAP patients. Conclusions:Dachengqi decoction could reduce inflammatory responses and promote recovery of intestinal microecological balance and gastrointestinal function in patients with MAP by regulating the composition of intestinal flora. No significant adverse effects were observed during the treatment period.

Objective:Efficacy and safety of robot-assisted laparoscopic adrenalectomy as a treatment for large adrenal tumors.Three-dimensional(3D) reconstruction can effectively assist in preoperative planning of robotic adrenalectomy and reduce potential complications.Methods:We retrospectively reviewed the relevant information of patients who had a preoperative 3D reconstruction and underwent RA for adrenal masses larger than 10 cm. Thirteen male patients and sixteen female patients were included. The median(range) age was 43(25, 57) years old and the median tumor diameter was 12.1(10.3, 16.2) cm. The patients underwent preoperative CT enhancement scanning, and three-dimensional images were reconstructed based on the examination data. Robot-assisted laparoscopic adrenalectomy was performed under general anesthesia in 29 cases in this cohort.Results:All surgeries were completed successfully without major complications such as massive bleeding, secondary surgery, or even patient death. The median operative time was 131 (80, 245) min, and the median intraoperative bleeding was 330 (50, 2 200 ml) ml. 9 patients received blood transfusions. There were 11 cases of pheochromocytoma (37.9%), 10 cases of adenocarcinoma (34.5%) as well as 2 cases of teratoma (6.9%) and 6 cases of cortical carcinoma (20.7%). The patients were followed up for a median of 30 months after surgery. Except for 3 cases lost to follow-up and 2 patients with cortical cancer who developed recurrence or metastasis after surgery and died at 16 and 23 months after surgery, respectively, the remaining 24 cases have survived to date.Conclusions:RA is a safe and effective treatment for huge adrenal tumors. The 3D reconstruction could help the preoperative planning of RA and reduce potential complications.

Objective To summarize the preliminary experience of extraperitoneal laparoscopic radical prostatectomy (C.R.P.C.four-step) for localized prostate cancer and the outcomes based on early follow-up.Methods A total of 102 prostate cancer patients were screened by prostate specific antigen (PSA) and diagnosed by prostate magnetic resonance imaging and prostatic puncture biopsy with cT1c-cT3b,with average age of (67 ±5) years old,average preoperative total PSA value of (45.32 ± 18.33) ng/ml,and average prostate volume was (42 ± 12)cm3.All these patients underwent extraperitoneal laparoscopic radical prostatectomy by the four-step technique,abbreviating as C.R.P.C.[C:control DVC (dorsal deep venous complex).R:recognize three anatomical layers (prostate and bladder junction,seminal vesicle,and Denonvilliers' fascia surface).P:preserve urethral sphincter and bladder neck.C:continuous anastomosis between urethra and bladder neck (4 key needles at 3,5,7 and 9 o'clock)].The operative time,estimated blood loss,length of hospital stay and postoperative complications were recorded,and the postoperative PSA was followed up.Results All the 102 cases were successfully treated by iaparoscopic radical prostatectomy.The operative time was from 55 to 156 min (mean 92 min),and the estimated blood loss was from 55 to 185 ml (mean 105 ml).There was no case converted of open surgery,only one case received blood transfusion for postoperative hemorrhage (0.98％),and positive surgical margin was found in 15 case (14.70％) by pathological examination.Postoperative urinary extravasation within one week occurred in 2 (1.96％) cases,and resolved after tensioning the catheter and prolonging the indwelling time.During the follow-up period of 12 to 45 months,2 cases were incontinent (grade I-II),and the other cases(98.04％) had no incontinence or dysuria.However,11 cases (10.78％) developed to biochemical recurrence within 6 months after the operation.Conclusions The C.R.P.C.four-step technique of lparoscopic radical prostatectomy is easily to be grasped and performed by the greenhand urologists,and was efficient and safe.