Objective To explore the effects of Kaixin Jieyu Pill(KJP)on peroxisome proliferator-activated receptor alpha(PPARα),serum and hippocampal tissue fibroblast growth factor 21(FGF21)and hippocampal tissue fibroblast growth factor receptor 1(FGFR1)in rats with depression model.Methods A rat chronic stress model was prepared using the chronic unpredictable mild stimulus method(CUMS)to observe behavioral changes in depression.Hippocampal FGF21,FGFR1 and liver PPARα protein and mRNA expression levels were measured in hippocampal tissues by western blot and real-time fluorescence quantification(RT-qPCT).Results The expression levels of PPARα,FGF21 and FGFR1's protein and their mRNA were dramatically decreased in the CUMS model rats compared with the normal group(P<0.001).KJP could modify the depressive-like behaviors of rats(P<0.001),upregulate the protein expression level of PPARα,FGF21,and FGFR1(P<0.05,P<0.01,P<0.01);markedly modify the mRNA expression levels of PPARα,FGF21,and FGFR1(P<0.001,P<0.01,P<0.01).Conclusion PPARα/FGF21/FGFR1 pathway may participate in the pathogenesis of depression;upregulation of PPARα/FGF21/FGFR1 pathway may be related to the antidepressant mechanism of KJP.

Objective To evaluate the dynamic efficacy of Invigorating Qi and Dissipating Depression Herbs in the treatment of depressive disorders and its effect on recurrence rate and suicidal thoughts.Methods The prospective cohort study was used to divide the patients into three cohorts according to the different exposure factors(treatment regimens):Western medicine group,integrated traditional Chinese and Western medicine group,and Invigorating Qi and Dissipating Depression Herbs group,and followed up for 2 years,and the treatment effects of each cohort at half a year,one year,one and a half years,and two years were observed respectively,and the evaluation indicators were Montgomery Depression Scale(MADRS),Hamilton Anxiety Scale(HAMA)and Social Deficit Screening Scale(SDSS)reduction rates,and endpoint events(relapse,suicidal ideation)incidence;By comparing the efficacy and endpoint event rate of the three cohorts,the effect of Invigorating Qi and Dissipating Depression Herbs on improving depressive disorders was evaluated.Results A total of 409 patients(67 in the Western medicine group,131 in the integrated traditional Chinese and Western medicine group,and 211 cases in the Invigorating Qi and Dissipating Depression Herbs group)were enrolled,and the rate of score reduction after treatment with MADRS,HAMA and SDSS increased compared with the pre-treatment treatment with the extension of the drug taking time.The difference between the MADRS and SDSS reduction rates in the Invigorating Qi and Dissipating Depression Herbs group on taking the drug for half a year and the SDSS reduction rate on one year of taking the drug were statistically significant compared with the Western medicine group,and there was no significant difference compared with the integrated Chinese and Western medicine group.On one and a half years and two years of medication,the integrated Chinese and Western medicine group had more advantages in MADRS reduction rate than the Invigorating Qi and Dissipating Depression Herbs group.The recurrence rates of depression in the three groups within 2 years were 20.9％,30.5％and 36.0％,and the difference was not statistically significant,and the length of taking medication was used as a protective factor by logistic regression analysis.The incidence rates of suicidal thoughts were 44.8％,19.1％and 17.5％,and the differences were statistically significant,and the exposure factors and income level were the protective factors by logistic regression analysis.Conclusion Invigorating Qi and Dissipating Depression Herbs can significantly improve the depressive state of patients,promote the recovery of social function,reduce the occurrence of long-term suicidal ideation,and appropriately extend the time of taking medicine can increase the long-term efficacy and reduce recurrence.

Objective : To analyze the overall survival( OS) of sequential osimertinib treatment in patients with epidermal growth factor receptor(EGFR) exon 20 T790M mutant advanced non⁃small cell lung cancer(NSCLC) and risk factors of the efficacy of sequential osimertinib treatment. Methods : The data of 138 advanced NSCLC patients with acquired EGFR exon 20 T790M mutation who took sequential osimertinib as second⁃line treatment. KaplanMeier variable was used for survival analysis. The Log⁃rank method was used for univariate analysis. The COX risk regression model was used for multivariate analysis. The survival status and influencing factors of patients treated with sequential osimertinib were analyzed. Results : At the last follow⁃up , 99 of the 138 patients died. Median progression free survival (PFS1)of first⁃line of first⁃ or second⁃generation epidermal growth factor receptor tyrosine kinase inhibitors(EGFR⁃TKIs) was 11 months (95% CI: 10. 1 - 11. 9) ; median PFS2 of osimertinib was 10 months (95% CI: 8. 5 - 11. 5) ; The median PFS with sequential osimertinib treatment was 24 months(95% CI: 21. 7 -26. 3) , the median OS was 32 months(95% CI: 28. 9 - 35. 1) . In univariate and multivariate analysis , PFS1 was an independent prognostic factor for PFS and OS(P < 0. 001) . Conclusion Sequential osimertinib treatment for advanced NSCLC patients with acquired EGFR exon 20 T790M mutation achieved good PFS(24 months) and OS (32 months) .

Humans ; Pulmonary Disease, Chronic Obstructive ; Smoke/adverse effects* ; Tobacco ; Tobacco Smoke Pollution

Objective:To summarize the experience of the precise prevention and control strategy of novel coronavirus infection in the pediatric intensive care unit(PICU)during the epidemic of the Omicron variant.Methods:A retrospective analysis was performed on the strategies and management experience of precise prevention and control of novel coronavirus infection in PICU at Pediatric Hospital of Fudan University from March 1 to May 10, 2022.Results:According to the national and Shanghai novel coronavirus infection prevention and control standards, the PICU in our hospital, in accordance with the specialty characteristics of PICU, cooperated with the hospital′s department of infection and medical department to jointly construct a precise ward management strategy for the outbreak of the omicron mutants infection.Precise prevention and control management strategies were formulated from four aspects: the admission process of critically ill children, the division of PICU ward areas and nosocomial infection protection, the reception management system for children′s family members, and the " bubble management" system for PICU staff, and run them for 3 months.During the epidemic, there was no nosocomial infection of novel coronavirus infection in children or medical staff.During the period, a total of 140 critically ill children were admitted, including 87 cases transferred from the general ward in the hospital, 48 cases from the emergency department(non-febrile, 3 cases transferred by the transfer team), four cases from fever clinic, and one case from control ward.Four of the critically ill children had no emergency nucleic acid test report when they were admitted to the PICU.Among the 140 critically ill children, 54 patients received mechanical ventilation, 18 patients received blood purification, and two patients were monitored after liver transplantation.Seventy-eight (55.7%) children had underlying diseases.Conclusion:During the current round of novel coronavirus epidemic in Shanghai, PICU in our hospital formulated the admission and ward management procedures for critically ill children, which ensured the prevention and control of nosocomial infection of novel coronavirus, and at the same time ensured the treatment of critically ill children to the greatest extent.

D-allulose-3-epimerase (DPEase) is the key enzyme for isomerization of D-fructose to D-allulose. In order to improve its thermal stability, short amphiphilic peptides (SAP) were fused to the N-terminal of DPEase. SDS-PAGE analysis showed that the heterologously expressed DPEase folded correctly in Bacillus subtilis, and the protein size was 33 kDa. After incubation at 40 °C for 48 h, the residual enzyme activity of SAP1-DSDPEase was 58%. To make the recombinant B. subtilis strain reusable, cells were immobilized with a composite carrier of sodium alginate (SA) and titanium dioxide (TiO2). The results showed that 2% SA, 2% CaCl2, 0.03% glutaraldehyde solution and a ratio of TiO2 to SA of 1:4 were optimal for immobilization. Under these conditions, up to 82% of the activity of immobilized cells could be retained. Compared with free cells, the optimal reaction temperature of immobilized cells remained unchanged at 80 °C but the thermal stability improved. After 10 consecutive cycles, the mechanical strength remained unchanged, while 58% of the enzyme activity could be retained, with a conversion rate of 28.8% achieved. This study demonstrated a simple approach for using SAPs to improve the thermal stability of recombinant enzymes. Moreover, addition of TiO2 into SA during immobilization was demonstrated to increase the mechanical strength and reduce cell leakage.
Bacillus subtilis/metabolism* ; Carbohydrate Epimerases/genetics* ; Enzyme Stability ; Enzymes, Immobilized/metabolism* ; Fructose ; Hydrogen-Ion Concentration ; Racemases and Epimerases ; Temperature

OBJECTIVE: To detect potential variant in an ethical Han Chinese pedigree affected with breast cancer. METHODS: The proband and her relatives were subjected to next-generation sequencing using a target capture sequencing kit containing 121 cancer-related genes. Candidate variants were selected by analysis of their type, frequency in population, and segregation with the phenotype. Candidate variant was verified by Sanger sequencing and TA cloning. RESULTS: A c.2013_2014ins GT variant was detected in the BRCA1 gene among all breast cancer patients from this pedigree but not among healthy females. The variant was not recorded in the 1000 Genome Project database or the Exome Aggregation Consortium (ExAC) database. The frameshifting insertion was predicted to form an premature stop codon in gene transcript and can give rise to a truncated protein. CONCLUSION The BRCA1 c.2013_2014ins GT variant probably underlies the pathogenesis of breast cancer in this Chinese pedigree.
Asian Continental Ancestry Group ; BRCA1 Protein ; genetics ; Breast Neoplasms ; genetics ; Exome ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Pedigree ; Phenotype

Objective:To investigate the association of left and right ventricular diameters in normal early pregnancy and early middle pregnancy to the biological growth parameters of fetus, and to establish the reference and Z-score model for left and right ventricles.Methods:Two hundred and forty-six fetuses in normal early pregnancy (11-13 + 6 weeks) and early middle pregnancy (14-17 + 6 weeks) from February 2019 to May 2019 in Sir Run Run Shaw Hospital were examined by routine ultrasound. Non-cardiac fetal biometric parameters included crown-rump length (CRL), biparietal diameter (BPD) and femoral length (FL) and gestation age (GA) based on menstrual age were assessed. The left and right ventricular widths (LVW, RVW) and ventricular lengths (LVL, RVL) were measured at the end of diastolic period by obtaining the standard four chamber view of fetal echocardiography. The end-diastolic areas (LVA, RVA) as the products of the ventricular widths and lengths, the global spherical indexes (GSI) of left and right ventricles (LVSI, RVSI), the ratios of left and right ventricular widths (LVW/RVW), the length ratios (LVL/RVL) and the area ratios (LVA/RVA) of both ventricles were calculated.GA, BPD and FL were used as independent variables. The predicted cardiac parameters and its derivative parameters were used as dependent variables. The corresponding reference range was established. The correlation between each standard deviation (SD) and independent variables was analyzed, and the corresponding Z-scores of left and right ventricular diameters were calculated by using the formula. Results:①LVW, RVW, LVL, RVL were found positively correlated with the increase of GA, BPD and FL, and the correlation between GA and LVW, RVW was the highest ( r=0.928, 0.930; all P<0.000 1). ②There was a positive correlation between LVA, RVA and GA ( r=0.868, 0.872; all P<0.000 1). LVSI, RVSI were found negatively correlated with GA ( r=-0.844, -0.861; all P<0.000 1), and LVSI>RVSI. LVW/RVW<1 and almost close to 1, the ratios decreased with the increase of GA( r=0.147, P<0.000 1). LVL/RVL>1, the ratios increased with the increase of GA( r=0.313, P<0.000 1). LVA/RVA>1, but there was no correlation with GA. ③The SD values of LVW, RVW, LVL, RVL positively correlated with independent variables. Taking GA and LVW as an example, the linear regression equation of LVW was Y=-5.338+ 0.549GA ( r=0.928, P<0.000 1), and the linear regression equation of LVW-SD was Y=-0.322+ 0.037GA( r=0.131, P<0.000 1). The Z-scores of LVW, RVW, LVL, RVL, LVA, RVA did not change with the changes of GA, BPD, and FL. Conclusions:The normal reference range and Z-scores of left and right ventricular lengths and widths can be simply and reliably established using statistical analysis, and these parameters might have potentials for more accurately and more early evaluating the normal development of fetal heart.

Objective:To investigate sedation level for postoperative patients with mechanical ventilation in ICU, and to explore the related factors and patient outcomes with different sedation level.Methods:Totally 163 postoperative ICU patients from 11th June to 30th October 2018 were prospectively analyzed. Medical information and all the RASS (Richmond Agitation Sedation Scale) scores was recorded by nurses.Results:The 163 enrolled patients received 11 261.62 hours mechanical ventilation therapy, and 2 815 RASS scores were assessed and recorded by nurses. Among these scores, 80.3% (2 261/2 815) were at light sedation level, while 17.4% (490/2 815) and 2.3% (64/2 815) were at excessive or insufficient sedation level, respectively. All patients were divided into satisfactory sedation group and unsatisfactory sedation group according to the recommendations of guidelines, and used both univariate analysis and multivariate analysis. Compared to males, female patients tend to be in a satisfactory sedation level ( OR value was 0.39, P<0.05); use of midazolam may increase the risk of unsatisfactory sedation level ( OR value was 5.60, P<0.05); the longer sedation assessment interval ( OR value was 1.70, P<0.05), the more likely the patient′s sedation level is unsatisfactory ( OR value was 1.70, P<0.05) . Patients in sedation unsatisfactory group have higher rate of tracheostomy ( χ 2 value was 9.70, P<0.01), longer ICU stay ( U value was -2.33, P<0.05) and more medical expense ( t value was -4.26, P<0.01). Conclusion:The current sedation management in our ICU is satisfactory, but there is still a small part of patients in a state of insufficient sedation or excessive sedation. Sedation level is closely related to sedatives, RASS assessments interval performed by the nurses. This study provides a reference and basis for clinical sedation management and the sedation assessment strategies in the ICU.

Objective:To investigate whether in vitro cultured human bone marrow mesenchymal stem cells (BMSCs) express sodium taurocholate cotransporting polypeptide (NTCP), assess their susceptibility to hepatitis B virus (HBV) infection and analyze the role of NTCP during HBV infection. Methods:BMSCs were infected with HBV-positive serum under different conditions. HBV DNA load in cell culture supernatants as well as in BMSCs and the amount of hepatitis B virus surface antigen (HBsAg) and hepatitis B virus e antigen (HBeAg) in cell culture supernatants were detected. To analyze the role of NTCP, BMSCs were first transfected with small interfering RNA targeting NTCP (NTCP-siRNA) and then infected with HBV-positive serum under different conditions. Virus loads and the amount of HBsAg and HBsAg were also detected. Western blot assay was performed to measure the expression of NTCP in BMSCs in each group.Results:In vitro cultured adherent BMSCs were susceptible to HBV infection albeit with a really low efficiency, but the infection efficiency was significantly increased when infecting the BMSCs in suspension. NTCP was expressed in BMSCs and the expression could be upregulated during HBV infection, especially in BMSCs in suspension. HBV infection was blocked when BMSCs were transfected with NTCP-siRNA. Conclusions:In vitro cultured human BMSCs were susceptible to HBV infection and the expressed NTCP served as a functional receptor for HBV. Human BMSCs could be used as a highly susceptible and stable cell model that needed no molecular adjuvant modification for research on the early stages of the HBV life cycle and for development of antiviral therapy.