Stigmasterol protects human brain microvessel endothelial cells against ischemia-reperfusion injury through suppressing EPHA2 phosphorylation / 中国天然药物

Stigmasterol is a plant sterol with anti-apoptotic, anti-oxidative and anti-inflammatory effect through multiple mechanisms. In this study, we further assessed whether it exerts protective effect on human brain microvessel endothelial cells (HBMECs) against ischemia-reperfusion injury and explored the underlying mechanisms. HBMECs were used to establish an in vitro oxygen and glucose deprivation/reperfusion (OGD/R) model, while a middle cerebral artery occlusion (MCAO) model of rats were constructed. The interaction between stigmasterol and EPHA2 was detected by surface plasmon resonance (SPR) and cellular thermal shift assay (CETSA). The results showed that 10 μmol·L-1 stigmasterol significantly protected cell viability, alleviated the loss of tight junction proteins and attenuated the blood-brain barrier (BBB) damage induced by OGD/R in thein vitro model. Subsequent molecular docking showed that stigmasterol might interact with EPHA2 at multiple sites, including T692, a critical gatekeep residue of this receptor. Exogenous ephrin-A1 (an EPHA2 ligand) exacerbated OGD/R-induced EPHA2 phosphorylation at S897, facilitated ZO-1/claudin-5 loss, and promoted BBB leakage in vitro, which were significantly attenuated after stigmasterol treatment. The rat MCAO model confirmed these protective effects in vivo. In summary, these findings suggest that stigmasterol protects HBMECs against ischemia-reperfusion injury by maintaining cell viability, reducing the loss of tight junction proteins, and attenuating the BBB damage. These protective effects are at least meditated by its interaction with EPHA2 and inhibitory effect on EPHA2 phosphorylation.

Pyridine pigments from functional Monascus rice / 药学学报

The trace chemical components in functional Monascus rice were studied to explore the potential bioactive substances. MCI column, Sephadex LH-20 gel, and preparative liquid chromatography were used to purified the ethyl acetate extract from functional Monascus rice. Two novel pyridine Monascus pigments were isolated and identified, named monascopyridine G (1) and monascopyridine H (2), respectively based on extensive mass spectrometry (MS), infrared radiation (IR), and nuclear magnetic resonance (NMR) analysis. The molecular docking experiments between compounds 1 and 2 and peroxisome proliferators-activated receptor-gamma (PPARγ) showed that they exhibited obvious binding force with the receptor protein. Besides, the biosynthetic pathways of the two compounds were proposed, which provide a valuable reference for the selective production of these potential bioactive substances.

Liver inflammation and fibrosis in HBV-infected patients with a low viral load / 临床肝胆病杂志

Objective To investigate liver inflammation and fibrosis in patients with chronic HBV infection with a low viral load. Methods Among the HBsAg-positive patients who attended Ganzhou Fifth People's Hospital from April 2019 to June 2022, 41 patients with 20 IU/mL 200-2 000 IU/mL and 4 (26.67%) had an HBV DNA level of 20-200 IU/mL; the patients with G2 liver inflammation accounted for 73.33% (11/15), and those with S2 liver fibrosis accounted for 46.67% (7/15); the patients with ALT ≤30 U/L accounted for 46.67% (7/15); the patients aged ≥30 years accounted for 86.66% (13/15); the patients with LSM > 17 kPa accounted for 6.67% (1/15), those with an LSM value of 12.4-17 kPa accounted for 46.67% (7/15), and those with an LSM value of 9.4-12.4 kPa accounted for 33.33% (5/15). Conclusion Patients with chronic HBV infection and low-level viremia have a relatively high risk of progression of inflammation and fibrosis. ALT level cannot be used as a basis for antiviral therapy in HBV-infected people with a low viral load. LSM based on transient elastography can be used as a noninvasive test to screen for CHB patients with a low viral load, and antiviral therapy should be considered when HBV-infected patients with a low viral load have an age of > 30 years and an LSM value of > 9.4 kPa persistently.

Comparison of squint angle measured by right angle prism and isosceles angle prism / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the differences in squint angle measured by right angle prism and isosceles angle prism.METHODS: Case control study. A total of 176 cases of concomitant strabismus admitted to our hospital from June 2021 to April 2022 were selected, among which 79 cases were concomitant esotropia and 97 cases were concomitant exotropia. The squint angle of all patients was measured respectively by alternating cover right angle prism and isosceles angle prism.RESULT: For patients with concomitant esotropia, the right angle prism degree was 49.167△±13.573△ and the isosceles angle prism degree was 38.250△±10.756△ (P<0.01), with a difference of 10.917△±3.752△; the measurement of right angle prism converted to circular degree was 19.096°±2.456°, and the isosceles angle prism value was 20.847°±5.364°(P<0.05), with a difference of 2.443°±2.702°. For patients with concomitant exotropia, the right angle prism degree was 51.875△±13.567△, and the isosceles angle prism degree was 40.492△±11.753△ (P<0.01), with a difference of 11.383△±4.783△; the measurement of right angle prism converted to circular degree was 19.589°±2.521°, and the isosceles angle prism value was 21.947°±5.864°(P<0.01), with a difference of 3.200°±3.077°. There was no significant statistical difference in the differences of the two prism degree and the circular degree for concomitant esotropia and concomitant exotropia(P>0.05).CONCLUSIONS: The squint angle measured by different shaped prisms is different. The degree measured by right angle prism is larger than that by isosceles angle prism.

Etiological diagnostic value of metagenomic next-generation sequencing in peritoneal dialysis-related peritonitis / 中华肝脏病杂志

Objective: To explore the etiological diagnostic value of metagenomic next-generation sequencing (mNGS) in peritoneal dialysis (PD)-related peritonitis. Methods: The study was a retrospective cohort study. The clinical data of patients with PD-related peritonitis who were treated and underwent microbial cultivation and mNGS test at the same time from June 2020 to July 2021 in the Affiliated Drum Tower Hospital, Medical School of Nanjing University were analyzed. The positive rate, detection time and consistency between mNGS test and traditional microbial culture were compared. Results: A total of 18 patients with age of (50.4±15.4) years old and median dialysis time of 34.0 (12.4, 62.0) months were enrolled in the study, including 11 males and 7 females. Pathogenic microorganisms were isolated in 17 patients by mNGS test, with a positive rate of 17/18, which was higher than 13/18 of microbial culture, but the difference was not statistically significant (P=0.219). Both mNGS test and microbial culture isolated positive pathogenic bacteria in 12 patients, and mNGS test isolated the same types of pathogenic bacteria as microbial cultivation did in 11 patients. In five patients with negative microbial culture, mNGS test also isolated pathogenic microorganisms, including 3 cases of Staphylococcus epidermidis, 1 case of Mycobacterium tuberculosis and 1 case of Ureaplasma urealyticum. In 1 patient, microbial culture isolated pathogenic bacteria (Escherichia coli) whereas mNGS test did not. The detection time of mNGS was 25.0 (24.0, 27.0) h, which was significantly shorter than 89.0 (72.8, 122.0) h of microbial culture (Z=3.726, P<0.001). Conclusions: mNGS test can improve the detection rate of pathogenic microorganisms in PD-related peritonitis and greatly shorten the detection time, and has good consistency with microbial culture. mNGS may provide a new approach for pathogen identification of PD-related peritonitis, especially refractory peritonitis.

Influencing factors of metabolic syndrome among adults in Nanjing， China： an analysis based on decision tree and logistic regress models / 上海预防医学

ObjectiveWe analyzed the prevalence of metabolic syndrome in adult residents of Nanjing and explored its influencing factors in order to provide technical references for the prevention of metabolic syndrome. MethodsBased on the data of the Nanjing adult chronic disease thematic survey from January 2017 to June 2018， the influencing factors of metabolic syndrome were analyzed using multifactorial logistic regression model and decision tree model. ResultsThe weighted prevalence of metabolic syndrome among people aged 18 years and over in Nanjing was 16.14%（95%CI：16.12%‒16.16%）. Prevalence of metabolic syndrome was statistically different（P<0.05）among respondents with different demographic characteristics. Logistic regression model analysis showed that age， gender， education， physical activity level， marriage status， smoking status， drinking status， weight status， diabetes and hypertension family history were the influencing factors for the prevalence of metabolic syndrome（P<0.05）. The results of the decision tree model showed that weight status was the most influential factor for metabolic syndrome， followed by age， gender， diabetes family history and smoking status. ConclusionThe prevalence of metabolic syndrome is high among the adult population in Nanjing， and special attention should be paid to middle-aged and elderly men who are overweight and obese， have a family history of diabetes and smoking.

Treatment of moderate functional mitral regurgitation during aortic valve replacement in patients with aortic valve disease: A retrospective cohort study / 中国胸心血管外科临床杂志

@#Objective    To evaluate the impact of different surgical strategies for moderate functional mitral regurgitation (FMR) at the time of aortic valve replacement (AVR) on patients' prognosis. Methods    A total of 118 AVR patients, including 84 males and 34 females, aged 58.1±12.4 years, who were complicated with moderate FMR were retrospectively recruited. Patients were divided into three groups according to the treatment strategy of mitral valve: a group A (no intervention, n=11), a group B (mitral valve repair, n=51) and a group C (mitral valve replacement, n=56). The primary endpoint was the early and mid-term survival of the patients, and the secondary endpoint was the improvement of FMR. Results    The median follow-up time was 29.5 months. Five patients died perioperatively, all of whom were from the group C. Early postoperative FMR improvement rates in the group A and group B were 90.9% and 94.1% (P=0.694). The mid-term mortality in the three groups were 0.0%, 5.9% and 3.9%, respectively (P=0.264), while the incidences of major cardiovascular and cerebrovascular events were 0.0%, 9.8% and 17.7%, respectively (P=0.230). Improvements of FMR in the group A and group B were 100.0% and 94.3% at the mid-term follow-up (P>0.05). Conclusion    For patients receiving AVR with moderate FMR, conservative treatment or concurrent repair of mitral valve may be more reasonable, while mitral valve replacement may increase the incidence of early and mid-term adverse events.

Preparation and intestinal absorption of Panax notoginseng saponins chitosan nanoparticles / 中国中药杂志

In this experiment, Panax notoginseng saponins chitosan nanoparticles(PNS-NPs) were prepared by self-assembly and their appearance, particle size, encapsulation efficiency, drug loading, polydispersity index(PDI), Zeta potential, and microstructure were characterized. The prepared PNS-NPs were intact in structure, with an average particle size of(209±0.258) nm, encapsulation efficiency of 42.34%±0.28%, a drug loading of 37.63%±0.85%, and a Zeta potential of(39.8±3.122) mV. The intestinal absorption of PNS-NPs in rats was further studied. The established HPLC method of PNS was employed to investigate the effects of pH, perfusion rate, and different drugs(PNS raw materials, Xuesaitong Capsules, and PNS-NPs). The absorption rate constant(K_a) and apparent permeability coefficient(P_(app)) in the duodenum, jejunum, ileum, and colon were calculated and analyzed. As illustrated by the results, the intestinal absorption of PNS-NPs was increased in the perfusion solution at pH 6.8(P<0.05), and perfusion rate had no significant effect on the K_a and P_(app) of PNS-NPs. The intestinal absorption of PNS-NPs was significantly different from that of PNS raw materials and Xuesaitong Capsules(P<0.05), and the intestinal absorption of PNS-NPs was significantly improved.

Improving the thermal stability of Proteus mirabilis lipase based on multiple computational design strategies / 生物工程学报

Proteus mirabilis lipase (PML) features tolerance to organic solvents and great potential for biodiesel synthesis. However, the thermal stability of the enzyme needs to be improved before it can be used industrially. Various computational design strategies are emerging methods for the modification of enzyme thermal stability. In this paper, the complementary algorithm-based ABACUS, PROSS, and FoldX were employed for positive selection of PML mutations, and their pairwise intersections were further subjected to negative selection by PSSM and GREMLIN to narrow the mutation library. Thereby, 18 potential single-point mutants were screened out. According to experimental verification, 7 mutants had melting temperature (Tm) improved, and the ΔTm of K208G and G206D was the highest, which was 3.75 ℃ and 3.21 ℃, respectively. Five mutants with activity higher than the wild type (WT) were selected for combination by greedy accumulation. Finally, the Tm of the five-point combination mutant M10 increased by 10.63 ℃, and the relative activity was 140% that of the WT. K208G and G206D exhibited certain epistasis during the combination, which made a major contribution to the improvement of the thermal stability of M10. Molecular dynamics simulation indicated that new forces were generated at and around the mutation sites, and the rearrangement of forces near G206D/K208G might stabilize the Ca2+ binding site which played a key role in the stabilization of PML. This study provides an efficient and user-friendly computational design scheme for the thermal stability modification of natural enzymes and lays a foundation for the modification of PML and the expansion of its industrial applications.

The effects of robotic-assisted versus laparoscopic-assisted radical right hemicolectomy on short-term outcome and long-term prognosis based on propensity score matching / 中华外科杂志

Objective: To compare the short-term and long-term outcomes between robotic-assisted and laparoscopic-assisted radical right hemicolectomy in patients with adenocarcinoma of the right colon. Methods: Retrospective review of a prospectively collected database identified 288 right colon cancer patients who underwent either robotic-assisted (n=57) or laparoscopic-assisted right hemicolectomy (n=231) between October 2014 and October 2020 at Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University. There were 161 males and 127 females, aging (60.3±12.8) years (range: 17 to 86 years). After propensity score matching as 1∶4 between robotic-assisted and laparoscopic-assisted right hemicolectomy, there were 56 cases in robotic group and 176 cases in laparoscipic group. Perioperative outcomes and overall survival were compared between the two groups using t test, Wilcoxon rank sum test, χ2 test, Fisher exact test, Kaplan-Meier method and Log-rank test, respectively. Results: The total operative time was similar between the robotic and laparoscopic group ((206.9±60.7) minutes vs. (219.9±56.3) minutes, t=-1.477, P=0.141). Intraoperative bleeding was less in the robotic group (50 (20) ml vs. 50 (50) ml, Z=-4.591, P<0.01), while the number of lymph nodes retrieved was significantly higher (36.0±10.0 vs. 29.0±10.1, t=4.491, P<0.01). Patients in robotic group experienced significantly shorter hospital stay, shorter time to first flatus, and defecation (t: -2.888, -2.946, -2.328, all P<0.05). Moreover, the overall peri-operative complication rate was similar between robotic and laparoscopic group (17.9% vs. 22.7%, χ²=0.596,P=0.465). The 3-year overall survival were 92.9% and 87.9% respectively and the 3-year disease-free survival rates were 83.1% and 82.6% with no statistical significance between the robotic and laparoscopic group (P>0.05). Conclusions: Compared to laparoscopic-assisted right hemicolectomy, robot-assisted right hemicolectomy could improve some short-term clinical outcomes. The two procedures are both achieving comparable survival.

Risk factors of residual tumor in single small hepatocellular carcinoma after thermal ablation treatment / 中华内科杂志

Objective:To evaluate the risk factors of residual tumor after thermal ablation in patients with small hepatocellular carcinoma.Methods:This was a retrospective study recruiting 107 patients diagnosed as single hepatocellular carcinoma with maximum diameter ≤3 cm from December 2009 to August 2015 in National Cancer Center. The cohort enrolled 81 males and 26 females, including 83 patients younger than 70 years old. All patients were treated with radiofrequency ablation or microwave ablation, and evaluated by CT or MRI after 4-6 weeks compared with baseline data. Potentially related factors were analyzed such as patients′ characteristics, tumor location and adjacent, ablation pattern, hepatitis B/C infection. A multivariate logistic regression analysis was conducted for the independence of risk factors.Results:Six patients (5.6%) with residual tumor was detected in the whole population of 101 cases. Univariate analysis suggested that tumor adjacent to vascular structure, poor differentiation, AFP≥200 μg/L were the risk factors of residue disease (all P<0.05). Multivariate logistic regression suggested that pathological type of poorly differentiated tumor was the only independent risk factor ( HR=2.26,95% CI 0.25-20.50, P=0.030). Conclusions:Poorly differentiated pathology is an independent predictive factor for residual disease in small hepatocellular carcinoma after thermal ablation. Such patients should be routinely followed up after operation.

Clinical application of dense fine spot anti-nuclear antibody in children with autoimmune diseases / 中华实用儿科临床杂志

Objective:To analyze the differences of the clinical characteristics and laboratory indexes in children with positive dense fine spot (DFS) type anti-nuclear antibody, and thereby to explore the value of positive DFS in the diagnosis of immunological diseases.Methods:Among 9 613 cases who were routinely tested for antinuclear antibody (ANA) from August 2017 to February 2020, there were 197 cases with DFS positive, who were subjected to a retrospective analysis.These patients were divided into the autoimmune diseases (AID) group (39 cases) and the non-AID group (158 cases) according to clinical diagnosis.Healthy children in the same physical examination were used as healthy control group (40 cases). T test was applied to analyze the differences of humoral immunity markers between AID and non-AID groups.What′s more, DFS positive patients in different clinical departments, initial symptom and the part of body were further compared. Results:Among 9 613 children tested for autoantibodies, 2 654 (27.61%) were ANA positive, with the highest detection rate of the spotted type and 197 DFS positive cases, accoun-ting for 7.42% of ANA positive children; 97 DFS positive male patients accounted for 8.20% (97/1 183 case) of ANA positive male patients, 100 DFS positive female patients accounted for 6.80% (100/1 471 cases) of ANA positive female patients, and there was no significant difference in the positive rate.The departments with high positive ANA detection included the nephrology department (27.88%) and the rheumatology department (24.83%). The departments with a higher ANA positive rate in DFS positive children included the gastroenterology department (13.25%) and the infectious department (11.76%). Among the children with DFS antibody positive, 39 cases had AID, among which 38 cases had organ-specific AID, and juvenile idiopathic arthritis (JIA) had the highest detection rate in 13 cases.The diseases with a high DFS positive rate in 158 non-AID cases included allergic purpura (46 cases). Serum immunoglobulin (IgG) level in the AID group was significantly lower than this in the non-AID group, serum IgM and C 4 levels in AID children were significantly lower than those in the non-AID group and healthy control group, and the serum IgA level of DFS positive group was significantly higher than that of children in the healthy control group.All children with DFS antibody positive had no specific autoantibodies. Conclusions:DFS antibody positive is important for the diagnosis of systemic AID in children.The combined detection with the DFS, other autoimmunity antibody index, humoral immune function index contributes to the early differential diagnosis of autoimmune diseases in children.

Current status of antimicrobial therapy for tuberculosis / 中国基层医药

Multidrug-resistant tuberculosis has a long treatment course and a low sputum-negative conversion rate, which have always been the treatment challenges. New drugs for multidrug-resistant tuberculosis have been constantly explored by scholars worldwide. Multiple antibacterial drugs have been found to have the therapeutic effects on multidrug-resistant tuberculosis. Treatment options that can shorten the duration of tuberculosis are also being explored. Addition of certain antibacterial drugs has been found to shorten the duration of tuberculosis. This paper reviews the effects of antibacterial drugs against tuberculosis.

Tocilizumab in patients with moderate or severe COVID-19: a randomized, controlled, open-label, multicenter trial / 医学前沿

Tocilizumab has been reported to attenuate the "cytokine storm" in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI-7.19%-21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 (P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI-99.17% to-17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.

Regulation of RNA Binding Protein Mbnl1 on Development of Mouse Embryonic Hematopoietic Stem Cells / 中国实验血液学杂志

OBJECTIVE@#To analyze the dynamic molecular expression characteristics of single cell RNA binding proteins (RBPs) in the development of mouse embryonic hematopoitic stem cells (HSCs), and obtain the functional research target RNA splicing factor--Mbnl1, to clarify the function of Mbnl1 involved in regulating mouse embryonic HSC development.@*METHODS@#Bioinformatics was used to analyze the single-cell transcriptome data of mouse embryos during HSC development, and the single-cell RBP dynamic molecular expression maps in HSC development was obtained. Mbnl1 was obtained by combining differential analysis and literature research screening. The Mbnl1-knockout mouse model was constructed by the CRISPER/Cas9 technology. Aorta-gonad-mesonephros (AGM) and yolk sac (YS) tissue in two genotype embryos of Mbnl1@*RESULTS@#The in vitro CFU-C experiment of hematopoietic cells preliminarily indicated that there was no significant difference in the number of cell colonies in AGM region and YS transformed by the two genotypes of Mbnl1@*CONCLUSION@#Through functional experiments in vivo and in vitro, it has been confirmed that knockout of the RNA splicing factor--Mbnl1 does not affect the development of HSPC in AGM region of mouse embryo.

S1 posterior edge inlet view for placement of percutaneous sacroiliac screws / 中华创伤骨科杂志

Objective:To evaluate the significance of S1 posterior edge inlet view for placement of percutaneous sacroiliac screws.Methods:1. CT data of the pelvis were collected from 134 normal adults and introduced into Mimics Medical 21.0 system. Anatomical parameters of sacral vertebrae were measured and analyzed to observe the anatomical disparities between the anterior and posterior edges of S1 vertebral body. A mathematical model was established using the data acquired. 2. Manual placement of sacroiliac screws was performed using a conventional S1 posterior edge inlet view on the pelvic specimens from 5 adult cadavers in simulation of actual surgical situations. After placement, the inlet views from both the S1 anterior and posterior edges were taken to observe the imaging differences and to check if the screws had pierced the sacral canal. 3. A retrospective study was conducted of the 11 patients with posterior pelvic ring fracture who had been treated at Department of Orthopaedics, Tongji Hospital from January 2019 to October 2020. Their fractures were fixated by percutaneous sacroiliac screws under the guidance of a C-arm X-ray machine. The manual placement of the screws was guided intraoperatively by the inlet views from both the S1 anterior and posterior edges to secure a safe placement. Pelvic CT examinations were performed to check any screw dislocation.Results:1. CT measurements in the normal adults showed that the angle of S1 anterior edge inlet view (20.71°±11.89°) was smaller than that of S1 posterior edge inlet view (41.99°±11.67°) and the width of S1 upper end plate [(32.22±3.41) mm] greater than that of S1 lower end plate [(20.10±3.28) mm], showing significant disparities in anatomy between the anterior and posterior edges of S1 vertebral body ( P<0.05). 2. In 2 of the 5 cadaveric specimens, imaging differences were observed between the inlet views of the anterior and posterior edges of S1 and the screws pierced out of the sacral canal. 3. Satisfactory closed reduction was achieved in all the 11 patients. A total of 17 screws were placed, with 12 ones into S1 and 5 ones into S2. Operation time ranged from 84 to 141 min (average, 114.4 min), fluoroscopy frequency from 69 to 101 times (average, 89.6 times), and intraoperative blood loss from 110 to 463 mL(average, 296.6 mL). No screw dislocation was observed on postoperative CT. Conclusion:As there is a difference between the inlet views of the anterior and posterior edges of S1 vertebral body, the inlet view of the posterior edge of S1 can display the posterior edge of S1 more clearly so as to improve the safety of placement of percutaneous sacroiliac screws.

Thinking on PBL teaching for health inspection and quarantine undergraduate / 中华医学教育探索杂志

This paper discusses from two aspects of case writing and PBL implementation experience. PBL cases should be based on professional requirements and reflect professional characteristics. Health inspection and quarantine cases targeted at application-oriented talent cultivation can be integrated into relevant experimental skills items. At the same time, the forms of case writing are expanded according to the differences of theme forms, which are designed as parallel cases and serial cases, so as to be applicable to the curriculum integration in different areas. In the implementation of PBL teaching, students' learning status is the key to the efficiency of classroom discussion, which determines whether the implementation of PBL is completely autonomous learning or embedded instruction. Teachers should establish cooperative learning atmosphere to improve the efficiency of classroom discussion

Research Progress in Genetic Research of Fatigue / 中国实验方剂学杂志

Fatigue refers to the manifestation of disorders in the process of carrying out or maintaining random activities， which can be regarded as an independent disease or as a symptom in a variety of chronic diseases. The high incidence of fatigue has seriously affected people's physical and mental health， and the prevention and treatment of fatigue has become an important problem to be solved urgently. The pathogenesis of fatigue mainly includes energy consumpation， accumulation of metabolites， abnormal secretion of neurotransmitters， decline of mitochondrial function， dysfunction of hypothalamus pituitary adrenal axis， etc. At present， there is no unified understanding about the pathogenesis of fatigue at home and abroad. The gene research of fatigue is the current research frontier. Gene expression profiling provides a new method for the study of the mechanism of fatigue. The combination of gene chip technology and traditional Chinese medicine（TCM） theory is expected to bring a breakthrough in the study of the pathogenesis of fatigue. In the study of fatigue gene chip， messenger RNA（mRNA） and microRNA（miRNA） are the common research objects， but few explorations are focused on the gene expression rule of fatigue by a specific signaling pathway and the effective regulation targets of TCM for treating fatigue. In recent years， the dysfunction of reward and inhibition mechanism in the central nervous system has become a research hotspot. In particular， gamma amino butyric acid （GABA） and dopamine （DA） have attracted much attention as the main substances of inhibition and reward mechanism， respectively. GABA and DA are used as inhibition and reward mechanisms to maintain the balance， and the body will not feel fatigue. Once the balance is broken， the fatigue will be formed. At the same time， DA and GABA receptors can also regulate cyclic adenosine monophosphate signaling pathway（cAMP） to affect fatigue. The research on key genes in GABA/DA balance mechanism and related cAMP signaling pathway by gene chip technology is expected to reveal the pathogenesis of fatigue in depth. The gene chip method is used to detect the changes of key genes in GABA/DA pathway and the related cAMP signaling pathway in the fatigue population and the normal population， so as to further explore the pathogenesis of fatigue. In this paper， the key genes in GABA/DA balance mechanism and cAMP signaling pathway related to fatigue were summarized by using the review method， so as to provide the basis for further study on the pathogenesis of fatigue and effective prevention and treatment from the perspective of genetics.

Research of Influence on Inflammation of Xieheyin on PCOS-IR Mice Based on Intestinal Mucosal Barrier and TLR4/NF-κB/NLRP3 Pathway / 中国实验方剂学杂志

Objective:To investigate the possible mechanism of Xieheyin in alleviating obese polycystic ovary syndrome with insulin resistance（PCOS-IR）and reducing inflammatory response. Method:Ten of sixty SPF femlae C57BL/6J mice were randomly selected as the normal group，and the rest mice were given letrozole 0.002 g·kg^-1 combined with fecal suspension 2 g·kg^-1 for 28 consecutive days to establish model of PCOS-IR.The mice that were successfully modeled were randomized into the model group，metformin group（0.25 g·kg^-1），and low（10 g·kg^-1），medium（20 g·kg^-1），and high-dose（40 g·kg^-1）Xieheyin groups，and administered with the corresponding drugs by gavage，once a day，for four consecutive weeks. Except the normal control group， the mice in the other groups were continuously given fecal suspension combined with letrozole solution to maintain the model during the treatment. The mice were weighed once a week.Levels of fasting blood glucose （FBG） were detected by blood glucose test strips.And enzyme-linked immunosorbent assay （ELISA） method was used to detect serum testosterone（T），follicle stimulating hormone（FSH），luteinizing hormone（LH），fasting insulin（FINS）level，and LH/FSH and Homeostasis model assesment of insulin resistance （HOMA-IR） were calculated．The uterus and ovaries were weighed and fixed.Hematoxylin-eosin（HE）staining was used to observe ovarian tissue pathology morphology. Western blot was used to detect the expression levels of tight junction key molecular zonula occludens 1（ZO-1），occludin in colon tissues，and the expression levels of Toll-like receptor 4/nuclear factor kappa B/Nod-like receptor protein 3（TLR4/NF-<italic>κ</italic>B/NLRP3）signaling pathway and inflammation associated proteins cysteinyl aspartate specific proteinase-1（Caspase-1） and interleukin-1<italic>β</italic>（IL-1<italic>β</italic>） in colon tissues. Result:Compared with normal control group，the body weight of mice in the model control group increased significantly（<italic>P</italic><0.01）. Serum FINS，FBG，HOMA-IR，T，LH/FSH were significantly increased（<italic>P</italic><0.05，<italic>P</italic><0.01）. The uterine organ ratio were decreased significantly（<italic>P</italic><0.01），while the ovarian organ ratio were significantly increased（<italic>P</italic><0.01）. The number of atresia follicles and cystic dilatation follicles increased significantly，and the number of corpus luteum significantly decreased，the thickness of follicular granulosa cells also decreased，while the white membrane thickness of the ovary increased. Tight junction related ZO-1，occludin proteins in colon tissues were all decreased（<italic>P</italic><0.01）.The relative expression levels of inflammation-related protein IL-1<italic>β</italic>，Caspase-1 and TLR4/NF-<italic>κ</italic>B/NLRP3 target protein signaling pathway were significantly increased（<italic>P</italic><0.05）.Compared with model control group， the body weight of mice in the low，middle and high dose Xieheyin group decreased significantly（<italic>P</italic><0.01）. The serum T，LH/FSH，FINS，FBG，HOMA-IR were significantly decreased（<italic>P</italic><0.05，<italic>P</italic><0.01）. The uterine organ ratio were increased（<italic>P</italic><0.05），while the ovarian organ ratio were decreased（<italic>P</italic><0.05）. The number of cystic follicles decreased and corpus luteum increased，the thickness of follicular granulosa cells increased and be arranged normally，while the white membrane thickness of the ovary increased slightly. The expressions of ZO-1，occludin proteins were increased（<italic>P</italic><0.01）. The expression levels of IL-1<italic>β</italic>，Caspase-1 and TLR4/NF-<italic>κ</italic>B/NLRP3 target protein in the high dose group were significantly decreased（<italic>P</italic><0.01）. Conclusion:Xieheyin could activate intestinal TLR4/NF-<italic>κ</italic>B/NLRP3 signaling pathway，inhibit pro-inflammatory factor secretion，improve obesity and IR，which was correlated with rebuilding intestinal mucosal barrier and inhibiting intestinal inflammation．

Perspectives on the construction of modern disease prevention and control system in Shanghai / 上海预防医学

It is a major public health task to promote the construction of modern disease prevention and control system in the prevention and control of the novel coronavirus pneumonia epidemic. In this study, we identified the current situation and challenges in the construction of disease prevention and control system in Shanghai, including the infrastructures, disciplines, human resources, information system, operational mechanism, and legalization. It is proposed that we should promote the construction of modern disease prevention and control system in Shanghai, which is aimed to improve the capacity in the disease prevention and control services, response to the major epidemics and public health emergencies, and scientific research in public health, in accordance with municipal functional orientation large-scale metropolitan public health security requirements in Shanghai. Moreover, we should promote policy-making, including upgrading infrastructures, facilitating discipline construction and scientific research innovation, optimizing development environment for human resources, accelerating comprehensive information construction, improving systems and mechanisms, and strengthening legal governance.