OBJECTIVE: To observe the effects of electroacupuncture (EA) on improving motor function and regulating microglial activation based on Notch receptor 1 (Notch1)/Hes family bHLH transcription factor 1 (Hes1) pathway in mice with Parkinson's disease (PD). METHODS: Thirty-six male C57BL/6 mice were randomly divided into a control group, a model group and an EA group, 12 mice in each group. PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days in the model group and the EA group. From the 1st day of modeling, EA was applied at "Baihui" (GV20) and bilateral "Shenshu" (BL23) in the EA group, with continuous wave, in frequency of 2 Hz and current of 2 mA, 15 min a time, once a day for 14 days continuously. The behavioral performance was evaluated by gait test, pole climbing test and hanging test, the number of positive cells of tyrosine hydroxylase (TH) and the co-expression positive cells of Notch1/ionized calcium binding adaptor molecule 1 (Iba-1) in the substantia nigra of midbrain was assessed by immunofluorescence, the protein expression of TH, α-synuclein (α-syn), Notch1, Hes1, Iba-1, inducible nitric oxide synthase (iNOS), Arginase-1 (ARG1), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10 was detected by Western blot, the mRNA expression of Notch1 and Hes1 was detected by real-time PCR. RESULTS: Compared with the control group, in the model group, the stride frequency was accelerated (P<0.001) and the stride length was shortened (P<0.001) for the four limbs, the pole climbing test time was prolonged (P<0.01) and the grip level was reduced (P<0.01); in the substantia nigra of midbrain, the number of positive cells of TH was decreased (P<0.001), the number of co-expression positive cells of Notch1/Iba-1 was increased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-1βand IL-6 was increased (P<0.01, P<0.05, P<0.001), the protein expression of TH, ARG1 and IL-10 was decreased (P<0.01, P<0.001), the mRNA expression of Notch1 and Hes1 was increased (P<0.01). Compared with the model group, in the EA group, the stride frequency was decelerated (P<0.001) and the stride length was increased (P<0.05, P<0.01, P<0.001) for the four limbs, the pole climbing test time was shortened (P<0.05) and the grip level was increased (P<0.05); in the substantia nigra of midbrain, the number of positive cells of TH was increased (P<0.01), the number of co-expression positive cells of Notch1/Iba-1 was decreased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-6 and IL-1β was decreased (P<0.05, P<0.01), the protein expression of TH, ARG1 and IL-10 was increased (P<0.05, P<0.001, P<0.01), the mRNA expression of Notch1 and Hes1 was decreased (P<0.05). CONCLUSION EA can improve the behavioral performance and protect the dopaminergic neurons in PD mice, its mechanism may relate to the inhibition of Notch1/Hes1-mediated neuroinflammation, thus inhibiting the microglial activation.
Animals ; Electroacupuncture ; Microglia/metabolism* ; Male ; Receptor, Notch1/metabolism* ; Parkinson Disease/physiopathology* ; Transcription Factor HES-1/metabolism* ; Mice ; Mice, Inbred C57BL ; Humans ; Signal Transduction

The American College Gastroenterology(ACG)recently released the 2024 edition of Guidelines for the management of acute pancreatitis.The guidelines first discuss the diagnosis,etiology,severity,and early management of acute pancreatitis,as well as the management of complications,especially pancreatic necrosis,and then the guidelines propose the clinical decisions such as antibiotics,nutrition,endoscopy,radiology,and surgical intervention.This article makes an excerpt of the key concepts and recommendations in the guidelines.

Objective:To analyze the risk factors of clinically significant bleeding in patients with severe acute pancreatitis (SAP).Methods:The clinical data of SAP patients who were managed at Changhai Hospital affiliated to Naval Medical University from January 1, 2014 to October 31, 2022 were retrospectively analyzed. Twenty-nine SAP patients with clinically significant bleeding were classified to form the bleeding group. There were 23 males and 6 females, aged (56.25±14.01) years old. Another 116 SAP patients with similar general data but with no clinically significant bleeding during the same hospitalization period were included to form the non-bleeding group based on a ratio of 1∶4. There were 94 males and 22 females, aged (56.14±13.96) years old in this non-bleeding group. The general data, modified CT severity index (MCTSI), bedside index for severity of acute pancreatitis (BISAP) and other clinical data of the two groups were collected to determine the risk factors of bleeding in SAP patients.Results:Of the 29 patients with bleeding, 6 had gastrointestinal bleeding, 14 had intra-abdominal bleeding, and 9 had mixed bleeding sites, 15 were cured and discharged, and 14 died. All the 29 SAP patients with bleeding received treatment using drugs. In addition, 8 patients underwent successful hemostasis using digital subtraction angiography, 3 underwent successful endoscopic hemostasis, 2 underwent successful surgical hemostasis, and 2 underwent successful conservative drug hemostasis. Multivariate logistic regression analysis showed that SAP patients with higher MCTSI ( OR=1.824, 95% CI: 1.187-2.802), longer prothrombin time (PT) ( OR=3.431, 95% CI: 1.470-8.007) and higher BISAP ( OR=2.286, 95% CI: 1.054-4.957) had an increased risk of bleeding (all P<0.05). Conclusion:The prognosis of SAP patients was compromised with bleeding. High MCTSI, prolonged PT, and high BISAP were independent risk factors for bleeding in SAP patients.

Objective:To evaluate the efficacy and safety of omeprazole and sodium bicarbonate suspension in the treatment of peptic ulcer.Methods:This present study was a multicenter, randomized, double-blind, double-dummy, positive drug parallel controlled phase Ⅱ clinical trial. According to different indications, the trial was divided into gastric ulcer (GU) and duodenal ulcer (DU) studies. Patients were stratified-block randomly divided with a 1∶1 ratio into experimental group and control group. The patients in the experimental group were administrated with omeprazole and sodium bicarbonate suspension omeprazole (20 mg for DU or 40 mg for GU, and 1 680 mg sodium bicarbonate) once a day. The patients in the control group received omeprazole magnesium enteric-coated tablet20 mg for DU or 40 mg for GU once a day. The treatment period was 4 weeks for DU and 8 weeks for GU. The main efficacy indicator was ulcer healing rate under endoscopy. The time of pain disappearance and the total effective rate of clinical symptom relief were used as the secondary efficacy indicators, and the incidence of adverse reactions was used as the safety indicator. The data set included full analysis set (FAS), per-protocol set (PPS) and safety set (SS). Independent sample t test, Wilcoxon rank sum test, chi square test, Fisher exact test method and non-inferiority test were used for statistical analysis. Results:Two hundred and seventy two DU patients and 237 GU patients were included in the FAS, 247 DU patients and 201 GU patients were included in the PPS, and 272 DU patients and 235 GU patients were included in the SS. The results of FAS analysis showed that after 4 weeks treatment, the healing rate of DU under endoscopy in the experimental group was 91.91% (125/136) and that in the control group was 94.85% (129/136), and the difference was not statistically significant ( P>0.05). After 8 weeks treatment the healing rate of GU under endoscopy in the experimental group was 86.44% (102/118) and that in the control group was 87.39% (104/119), and the difference was not statistically significant ( P>0.05). The results of non-inferiority analysis showed the lower limit of 95% confidence interval of difference in effective rate between the two groups was over -10% (-8.84% for DU and -9.54% for GU), which indicated that the effective rate of experimental group was not inferior to that of the control group. The results of PPS analysis were consistent with the results of FAS. The results of FAS analysis showed the median time of abdominal pain disappearance of DU patients in the experimental group and the control group was both 6 d, and the difference was not statistically significant ( P>0.05). The median time of abdominal pain disappearance of GU patients in the experimental group and the control group was both 8 d, and the difference was not statistically significant ( P>0.05). After 4 weeks of treatment, the total effective rates of clinical symptom relief of DU of the trial group and the control group were 95.59% (130/136) and 97.79% (133/136), respectively, and the difference was not statistically significant ( P>0.05). After 8 weeks of treatment, the total effective rates of clinical symptom relief of GU of the experimental group and the control group were 95.76% (113/118) and 93.28% (111/119), respectively, and the difference was not statistically significant ( P>0.05). The results of SS analysis showed that the incidence of adverse reactions of DU patients in the trial group and the control group was 5.15% (7/136) and 2.21% (3/136), respectively, and the difference was not statistically significant ( P>0.05). The incidence of adverse reactions of GU patients in the experimental group and the control group was 12.71% (15/118) and 6.84% (8/117), respectively, and the difference was not statistically significant ( P>0.05). Conclusions:Omeprazole and sodium bicarbonate suspension is not inferior to omeprazole magnesium enteric-coated tablet in healing efficacy under endoscopy in peptic ulcer, and has a good safety.

Objective:To investigate the predictive value of acute gastrointestinal injury (AGI) score for the severity of acute pancreatitis (AP), infectious pancreatic necrosis and patients′ death.Methods:Clinical data of 719 patients with AP were collected from the AP database of the National Clinical Research Center for Digestive System Diseases from January 2016 to June 2018. According to the severity of the disease, they were divided into MAP group (506 cases), MSAP group (112 cases) and SAP group (101 cases). AGI, APACHEⅡ, MCTSI and BISAP scores were calcululated in the three groups. Receiver operating characteristic curve (ROC) was drawn and the area under the curve (AUC) was calculated. The predictive value of the above four scoring systems for the hospitalization days, disease severity, infectious pancreatic necrosis and death was analyzed, respectively.Results:There were no cases of infectious pancreatic necrosis or death in the MAP group, but there were 9 cases of infectious pancreatic necrosis and 2 deaths in the MSAP group and 19 cases of infectious pancreatic necrosis and 8 deaths in the SAP group. There was a strong correlation between AGI score and AP patients′ hospitalization days ( r=0.619). AUC of AGI, APACHEⅡ, MCTSI and BISAP score in predicting the AP patients′ severity (MSAP+ SAP) was 0.967 (95% CI 0.951-0.982), 0.769(95% CI 0.720-0.899), 0.842(95% CI 0.809-0.875), 0.862 (95% CI0.832-0.893). AUC for forecasting infectious pancreatic necrosis was 0.803, 0.677, 0.692, 0.724, and the 95% CI was 0.724-0.882, 0.573-0.781, 0.582-0.636, 0.801-0.812. AUC for predicting death in patients with AP were 0.915, 0.597, 0.659, 0.812, and the 95% CI were 0.843-0.986, 0.444-0.751, 0.498-0.698 and 0.882-0.926. AGI score had the highest predictive value, followed by BISAP score, and the correlation between these two scores was the closest. The predictive value of AGI combined with BISAP score for infectious pancreatic necrosis and patient death (AUC were 0.837, 0.942, 95% CI were 0.770-0.903, 0.897-0.987) was better than that of AGI and BISAP score alone. Conclusions:AGI score combined with BISAP score is more effective in predicting the severity of AP, the occurrence of infectious pancreatic necrosis or patient death.

Objective:To investigate the normal range of fetal ventricles and posterior cranial fossa development in the second and third trimesters and their variations with gestational age using quantitative MRI analysis.Methods:This retrospective study enrolled 675 pregnant women who underwent prenatal MRI examination with an average gestational week of 29.0±8.5 in the Third Affiliated Hospital of Guangzhou Medical University from January 2016 to January 2020. MRI data of all the subjects were collected and analyzed, including left lateral ventricle trigonometric width (LLVTW) and right lateral ventricle trigonometric width (RLVTW), third ventricle width (TVW), fourth ventricle width (FVW), the anterior-posterior diameter of the fourth ventricle (APDFV), cavum septum pellucidum width (CSPW), cisterna magna width (CMW), etc. Spearman, Pearson correlation analysis, and t-test were used for the statistical analysis. Results:(1) Totally 675 fetuses were recruited, including 392 female and 283 male fetuses. No statistical difference of gestational weeks at MRI was found between male and female fetuses. (2)The mean value of TVW and CMW of the female fetuses were significantly higher than those of male fetuses [(0.60±0.05) vs (0.63±0.04) cm, t=－5.059; (0.57±0.14) vs (0.67±0.15) cm, t=－7.445; both P<0.001]. Spearman correlation analysis showed that TVW and CMW were negatively correlated with fetal gender ( r=－0.179 and－0.312, both P<0.001). (3)Pearson correlation analysis showed that LLVTW, RLVTW, TVW, FVW, APDFV, CSPW, and CMW were all positively correlated with gestational weeks ( r=0.310, 0.267, 0.205, 0.801, 0.829, 0.216 and 0.284, all P<0.001). FVW and APDFV were significantly linearly correlated with gestational weeks (r=0.801 and 0.829, both P<0.001). (4) There was no significant change in LLVTW and RLVTW in the second trimester, but a slight increase was found in the third trimester. TVW showed a scattered distribution in the second and third trimesters and increased slightly with the gestational week at 26 to 27 +6 gestational weeks. FVW and APDFV increased linearly while. CSPW increased slowly with gestational weeks in the second and third trimesters. CMW increased slightly with gestational weeks in the second and third trimesters but showed little change in the third trimester. Conclusions:The development of fetal ventricles and posterior cranial fossa in the second and third trimesters show a growth trend of varying degrees with the increase of gestational weeks. TVW and CMW are significantly negatively correlated with the fetal gender.

Objective:To explore the expression of miR-216a in patients with acute pancreatitis (AP) associated with acute lung injury (ALI) and its influence on endothelial cells permeability.Methods:40 AP patients admitted in Department of Gastroenterology of the First Affiliated Hospital of Navy Medical University from December 2015 to March 2016 were collected and were classified into AP with ALI (AP-ALI group, n=13) and AP without ALI (AP group, n=27) according to the presence or absence of ALI. 8 normal volunteers were enrolled in the control group. Blood samples were collected and the plasma samples were separated. Plasma RNA was extracted. miR-216a level in plasma was detected by RT-PCR. Plasma exosomes were extracted by exosome extraction kit and identified by the electron microscopy. Exosome RNA was extracted. miR-216a level in exosome was detected by RT-PCR. Plasma exosomes of AP-ALI patients were co-cultured with human umbilical vein endothelial cells (HUVEC, AP-ALI-HUVEC group) and anti-miR-216a transfected HUVECs (AP-ALI-anti-miR-216a HUVEC group) for 24 hours, respectively, and untreated HUVECs served as control group. Trans-endothelium electrical resistance (TEER) was measured by Millicell Ers-2 epithelial volt-ohmmeter to evaluate the cell permeability. Results:RT-PCR results showed that the expression level of plasma miR-216a in AP-ALI group (14.45±1.64) was significantly higher than that in AP group (11.08±1.6) and the control group (5.37±1.54) ( P<0.01). Under electron microscope, plasma exosomes were goblet like vacuoles, with the size of about 50-90 nm. The plasma exosomal miR-216a level in the AP-ALI group (14.03±1.58) was significantly higher than that in the AP group (10.86±1.31) and the control group (5.01±0.79), and the difference was statistically significant ( P<0.01). The resistance value of HUVEC in the control group was referred as 1, and the resistance ratio of HUVEC in AP-ALI-HUVEC group was 0.74±0.04, which was significantly lower than that of HUVEC in AP-ALI-anti-miR-216a HUVEC group (1.02±0.08), the difference was statistically significant ( P<0.01). Conclusions:miR-216a was highly expressed in plasma exosomes of AP patients with ALI. miR-216a can increase endothelial cell permeability, which may be associated with ALI during AP.

Objective To investigate the current status and characteristics of the immersion experience of medical students and related influencing factors. Methods The stratified random sampling method was used to conduct a survey using an immersion experience questionnaire among 732 medical students in a full-time university. Epidata 3.1 software was used for data double entry and management, and SPSS 19.0 statistical software was used for data processing and statistical analysis. The questionnaire internal consistency reliability test was used to assess the validity of the questionnaire and a logistic regression analysis was used to identify the influencing factors for the immersion experience of medical students. Results Learning immersion experience was at a moderate level among the medical students (3.13±0.64). Level of performance (OR=1.177, 95％CI=0.988-1.402), degree of satisfaction with learning (OR=1.674, 95％ CI=1.341-2.089), and professional interest (OR=2.153, 95％CI=1 . 776-2 . 610 ) were the positive influencing factors for learning immersion (P<0.05) and were positively correlated with learning immersion experience . Grade , source of origin , duty , learning stress , school satisfaction, and life satisfaction had no influence on learning immersion experience (P>0.05). Conclusion Learning immersion experience is at a moderate level among medical students. Improvement of medical students' performance, learning satisfaction,and professional interest helps to improve their immersion experience. Strengthening the attention to work immersion and enhancing learning immersion experience among medical students are beneficial to medical student education and cultivation of qualified medical talents.

Objective The aim of this study is to explore the mechanism of canonical Wnt signaling pathway in type 2 diabetes mice peripheral neuropathy. Methods Male C57BL6 mice were randomly assigned to three groups. One group treated with normal diet as control. And the rest were used to establish the diabetic model through the combination of 60 kcal% high fat diet and an administration of multipleand low dose of streptozotocin on 5 consecutive days. When the model of type 2 diabetes mice peripheral neuropathy was successfully established, one group was injected with the canonical Wnt signaling pathway inhibitor XAV 939 ( T2DM-XAV 939 group) and the other one was injected with phosphate buffer saline (PBS) as control (T2DM-PBS group). The 21stweek was the end point of the experiment, and fasting blood glucose, insulin level, homeostasis model assessment for insulin resistance (HOMA-IR), plantar test, and exercise tolerance were measured, realtime PCR were adopted to detect the related mRNA expression of the canonical Wnt signaling pathway. Results T2DM-XAV 939 group had higher total cholesterol, triglyceride, fasting blood glucose, and HOMA-IR than T2DM-PBS group, but showed no statistical difference. The enzymatic activity of glutamic oxaloacetic transaminase was lower level than that in T2DM-PBS group (P＜0.05); T2DM-XAV 939 group had significantly higher plantar test and poorer exercise tolerance than those in T2DM-PBS group (P＜0.05). The mRNA levels of genes in canonical Wnt signaling pathway such as β-catenin, c-myc, mitochondrial transcription factor A (TFAM) had slightly lower level than those in T2DM-PBS group, without statistical difference, and the protein expression of c-myc was lower than that of T2DM-PBS group (P＜0.05). The insulin receptor substeate 2 (IRS-2) mRNA expression was higher than that in T2DM-PBS group (P＜0.05). With the development of the experiment, we found that the survival rate of the T2DM-XAV 939 group was significantly reduced compared with the other groups. Conclusion Inhibition of the canonical Wnt signaling pathway may aggravate diabetic peripheral neuropathy.