Objective To investigate the effect of chronic atrial fibrillation on free calcium concentration and expression of Ca 2+ /calmodulin dependent protein kinase Ⅱ (CaMKⅡ) in human atrial myocytes. Methods The intracellular free calcium concentration in rapidly isolated atrial myocytes and the expression of CaMKⅡ in atrial tissue of rheumatic heart disease patients with atrial fibrillation (AF) or with normal sinus rhythm were measured by laser scanning confocal microscopy and Western blotting respectively. Results The intracellular Ca 2+ concentration of patients with atrial fibrillation was significantly higher than that of patients with normal sinus rhythm [(276.38?38.12) vs (122.28?45.63) nmol/L, (P

AIM: To investigate the effect of chronic atrial fibrillation (AF) on free calcium concentration and expression of Ca 2+ /calmodulin dependent protein kinase Ⅱ (CaMKⅡ) in human atrial myocytes. METHODS: The intracellular free calcium concentration in acute isolated atrial myocytes and the expression of CaMKⅡ in atrial tissue of rheumatic heart disease patients with atrial fibrillation (AF) and with normal sinus rhythm were measured by laser scanning cofocal microscopy technique and Western blotting, respectively. RESULTS: The intracellular Ca 2+ concentration in patients with atrial fibrillation was significantly higher than that in patients with normal sinus rhythm [(276.38?38.12) nmol/L vs (122.28?45.63) nmol/L, P

OBJECTIVE: To investigate the clinical and pathological features of solitary pterygoid benign lesions, as well as the treatment and outcome of endoscopic surgery. METHOD: We retrospectively analyzed clinical data of 4 patients with pterygoid benign lesions in our department. High resolution CT and enhanced MRI were performed before the operations, then endoscopic surgeries were carried out under the circumstance of general anesthesia. After a follow-up in 12 months to 48 months, nasal endoscopy and MRI examination were performed. Therefore we are able to understand the situation of operations and postoperative recurrences, and to inquire about the changes of symptoms and the relief of symptoms before and after surgery. RESULT: From the Pathological diagnosis, it showed 2 cases of cystic lesions, 1 case of spindle cell lipoma, 1 case of inflammatory lesion. Postoperative follow up showed scar formation, smooth surface, no recurrence, and no new symptom. Nasal obstruction is relieved after the surgery, and no changes in the sympotoms of headache were observed. CONCLUSION The combination of high resolution CT with enhanced MRI isimportant for ascertaining the location, extent and nature of the pterygoid lesions. Endoscopic surgery is a minimally invasive, safe, and effective method for the treatment of solitary pterygoid benign lesions.
Cysts ; diagnosis ; surgery ; Endoscopy ; Headache ; Humans ; Lipoma ; diagnosis ; surgery ; Magnetic Resonance Imaging ; Nasal Obstruction ; diagnosis ; surgery ; Nasal Surgical Procedures ; Neoplasm Recurrence, Local ; Nose ; Postoperative Period ; Retrospective Studies ; Tomography, X-Ray Computed

Objective:To investigate the clinical efficacy of the combination therapy of lenvatinib and programmed death-1 (PD-1) antibodies in unresectable or advanced hepatocellular carcinoma (HCC).Methods:The retrospective and descriptive study was conducted. The clinico-pathological data of 59 patients with unresectable or advanced HCC who were admitted to Zhongshan Hospital of Fudan University from September 2018 to January 2020 were collected. There were 54 males and 5 females, aged from 25 to 73 years, with a median age of 52 years. All 59 patients underwent combination therapy with lenvatinib and PD-1 antibodies including 43 cases undergoing first-line therapy and 16 cases who cannot tolerate first-line therapy or with tumor progressed after first-line therapy undergoing second-line therapy. Observation indicators: (1) clinical efficacy; (2) adverse drug reactions and treatment; (3) follow-up and survival. Follow-up was performed using outpatient examination or telephone interview to detect tumor diameter of the target lesion, overall survival and progression free survival of patients up to December 2020. Measurement data with skewed distribution were expressed as M ( P25,P75) or M (range). Count data were represented as absolute numbers and (or) percentages. The Kaplan-Meier method was used to calculate the median duration of response (DoR), median overall survival time, median progression free survival time, survival rates and draw survival curves. Results:(1) Clinical efficacy: the objective response rate (ORR), complete response rate (CR), partial response rate (PR), stable disease rate (SD), progression disease rate (PD), time to response (TTR) and median DoR of 59 HCC patients were 37.3%(22/59), 11.9%(7/59), 25.4%(15/59), 37.3%(22/59), 25.4%(15/59), 2.6 months(2.1 months, 4.0 months), 6.3 months[95% confidence interval ( CI) as 2.2 to 10.5 months], respectively. The ORR, CR, PR, SD, PD and TTR of 43 HCC patients undergoing first-line therapy were 41.9%(18/43), 16.3%(7/43), 25.6%(11/43), 37.2%(16/43),20.9%(9/43), 2.2 months(2.0 months, 3.5 months), respectively. The median DoR of 43 patients undergoing first-line therapy was not reached. The ORR, CR, PR, SD, PD, TTR and median DoR of 16 HCC patients undergoing second-line therapy were 4/16, 0, 4/16, 6/16, 6/16, 3.8 months (3.6 months, 4.1 months), 4.2 months(95% CI as 2.0 to 6.3 months), respectively. Six of 59 HCC patients underwent R 0 resection due to tumor converting to resectable HCC with the conversion and resection rate of 10.2%(6/59). Among the 6 patients, 5 cases undergoing first-line treatment had the conversion and resection rates of 11.6% (5/43) and 1 case undergoing second-line treatment had the conversion and resection rates of 1/16, respectively. (2) Adverse drug reactions and treatment: 25 of 59 HCC patients underwent 3 to 4 grade adverse drug reactions with the incidence of 42.4%(25/59). Among the 25 patients, 10 cases including 5 cases undergoing first-line therapy and 5 cases undergoing second-line therapy had the level of gamma glutamyltransferase >5×upper limit of normal (ULN), 9 cases including 4 cases undergoing first-line therapy and 5 cases undergoing second-line therapy had the level of aspartate aminotransferase >5×ULN, 5 cases including 4 cases undergoing first-line therapy and 1 case undergoing second-line therapy occurred gastrointestinal hemorrhage, 4 cases undergoing first-line therapy had the level of white blood cell count <2.0×10 9/L, 4 cases including 1 case undergoing first-line therapy and 3 cases under-going second-line therapy had the level of total bilirubin >3×ULN, 3 cases undergoing first-line therapy had the level of neutrophil count <1.0×10 9/L, 3 cases including 2 cases undergoing first-line therapy and 1 case undergoing second-line therapy occurred ascites, 2 cases including 1 case undergoing first-line therapy and 1 case undergoing second-line therapy had the level of platelet count <50.0×10 9/L, 2 cases undergoing first-line therapy had the level of alanine aminotransferase >5×ULN, 2 cases undergoing first-line therapy occurred hyponatremia, 2 cases including 1 case undergoing first-line therapy and 1 case undergoing second-line therapy occurred pulmonary infection, 2 cases including 1 case undergoing first-line therapy and 1 case undergoing second-line therapy occurred type 1 diabetes, 1 case undergoing first-line therapy occurred hypokalemia, 1 case undergoing first-line therapy occurred myocarditis, 1 case undergoing first-line therapy occurred hypophysistis, 1 case undergoing first-line therapy occurred bullous dermatitis, 1 case undergoing first-line therapy occurred hypertension. Three of 59 HCC patients underwent 5 grade adverse drug reactions ,with the incidence of 5.1%(3/59), including 1 case undergoing first-line therapy with immune hepatitis, 1 case undergoing second-line therapy with immune pneumonia and 1 case undergoing second-line therapy with immune enteritis. Some of patients underwent multiple adverse drug reactions at the same time. Twenty five patients undergoing 3 to 4 grade adverse drug reactions were relieved with the treatment of drug reduction, drug withdrawal, symptomatic treatment or hormone therapy. Three patients undergoing 5 grade adverse drug reactions died after being treated with high-dose hormone shock and hepatoprotective treatment. (3) Follow-up and survival: all 59 patients were followed up for 1.5 to 25.2 months, with a median follow-up time of 13.3 months. Of them, patients undergoing first-line therapy were followed up for 1.9 to 25.2 months, with a median follow-up time of 13.5 months. During follow-up,20 cases undergoing first-line therapy died with the fatality rate of 46.5%(20/43). Patients undergoing second-line therapy were followed up for 1.5 to 24.4 months, with a median follow-up time of 10.8 months. During follow-up, 10 cases undergoing second-line therapy died with the fatality rate of 10/16. Up to the latest follow-up, the tumor diameter of the target lesion in all 59 patients, in patients undergoing first-line therapy and in patients undergoing second-line therapy was 75 mm(38 mm, 125 mm), 74 mm(36 mm, 116 mm), 84 mm(48 mm,150 mm), respectively. The ratio of tumor diameter of the target lesion at latest follow-up to tumor diameter of the target lesion at baseline were -9.05%(-27.3%, 19.7%), -16.1%(-28.8%, 13.6%), 13.2%(-24.7%, 23.5%) for all 59 patients, patients undergoing first-line therapy and patients undergoing second-line therapy, respectively. The median overall survival time and median progression free survival time of patients undergoing first-line therapy and patients undergoing second-line therapy were 17.1 months(95% CI as 11.0 to 23.2 months), 10.8 months(95% CI as 5.0 to 16.6 months) and 10.8 months(95% CI as 9.2 to 12.4 months), 3.0 months(95% CI as 1.6 to 4.4 months), respectively. Conclusion:For unresectable or advanced HCC, combination therapy with lenvatinib and PD-1 antibodies can obtain effective antitumor activity and less incidence of adverse drug reactions.

OBJECTIVEFactor VIII( FVIII) gene knockout mouse model was established for further study on the treatment of hemophilia A.

METHODSExons 16-19 of the mouse FVIII gene were knocked out by ET clone, ES homologous recombination and tetraploid embryo compensation technology. PCR, reverse transcriptase-PCR(RT-PCR) and immunohistochemistry were used to detect the transcription and translation pattern of FVIII. The phenotype of the knockout mice was analyzed by examining the activated partial thromboplastin time (APTT) and FVIII activity (FVIII:C).

RESULTSPCR, RT-PCR and immunohistochemistry confirmed that FVIII was deficient in the FVIII gene knockout mouse. The APTT results showed that FVIII-deficient mouse plasma had a prolonged clotting time compared to normal mouse plasma. The FVIII:C in heterozygous, hemizygous and homozygous mice was 80%, 8% and 10% of that in normal mice, respectively.

CONCLUSIONThe phenotype of the FVIII gene knockout mouse appears grossly similar to that of human with hemophilia A. Establishment of this model may promote the development of new technologies of treatment to hemophilia A.

Animals ; Disease Models, Animal ; Embryo, Mammalian ; Factor VIII ; genetics ; metabolism ; Female ; Hemophilia A ; genetics ; metabolism ; physiopathology ; Humans ; Male ; Mice ; Mice, Inbred ICR ; Mice, Knockout ; Partial Thromboplastin Time

Objective To evaluate the mechanism of governor vessel electroacupuncture in rats with post-stroke limb spasm by observing the changes of glutathione antioxidant system-related factors.Methods A total of 60 SD rats were randomly divided into the normal group(n=12),sham operation group(n=12)and modeling group(n=36).The middle cerebral artery obstruction model was prepared by thread approach method in the modeling group,and 24 rats with successful modeling were randomly divided into the model group and the electroacupuncture group,with 12 rats in each group.At the 3rd day after modeling,the electroacupuncture group was treated with electroacupuncture at three acupoints of the governor vessel,namely,"Dazhui"(GV14),"Jizhong"(GV6)and"Houhui"(anteromedial of the transverse process of the sixth lumbar vertebra),for 30 min each time,once a day for 7 days.The neurological function of rats was assessed by Zea Longa neurological deficit score.The muscle tension of rats was detected by modified Ashworth dystonia rating and electrophysiological tracing method.The brain tissue water content was measured by the dry-wet weight method.The volume of cerebral infarction of rats was measured by the TTC staining method.The contents of glutathione(GSH),catalase(CAT),oxidized glutathione(GSSG),superoxide dismutase(SOD),and malondialdehyde(MDA)in the cortex of rats were detected by colorimetry.The protein and mRNA expressions of glutathione reductase(GR),glutamate cysteine ligase(GCL)C,GCLM,and glutathione peroxidase 4(GPX4)in the cortex of rats were measured by Western blotting and real-time PCR,respectively.Results Compared with rats in the normal and sham operation groups,the Zea Longa neurological deficit score,modified Ashworth dystonia rating,the volume of cerebral infarction,brain tissue water content,and GSSG and MDA contents in cortex were increased in the model group,the tension signal value and the proteins and mRNA expressions of GR,GCLC,GCLM,and GPX4 in cortex were decreased,and the contents of GSH,CAT,and SOD in cortex were decreased(P＜0.05).Compared with the model group,the Zea Longa neurological deficit score,modified Ashworth dystonia rating,the volume of cerebral infarction,brain tissue water content,and GSSG and MDA contents in cortex were decreased in the electroacupuncture group,the tension signal value and the proteins and mRNA expressions of GR,GCLC,GCLM,and GPX4 in cortex were increased,and the contents of GSH,CAT,and SOD in cortex were increased(P＜0.05).Conclusion Governor vessel electroacupuncture can improve the severity of post-stroke limb spasm in rats,and its mechanism may be related to the regulation of glutathione antioxidant system in cerebral cortex.

Objective To study the protective effects of sevoflurane at different anesthesia depths on periperative myocardial ischemia in coronary heart disease patients undergoing noncardiac surgery.Methods 96 patients with coronary undergoing noncardiac surgery were randomly divided into three groups:control group (Group C),high-concentration sevoflurane group (Group S 1) and low-concentration sevoflurane group (Group S2).Etomidate,Propofol,Cisatracurium Besilate and Fentanyl were used for intravenous anesthetic induction and maintenance of anesthesia.In addition,B ispectralindex (BIS) remained between 35 ～ 45 and 45 ～ 55 in groups S1 and S2,re spectively.BIS remained between 40 ～ 50 in group C.Perioperative hemodynamic changes,ECG ST-segment before induction of anesthesia,endotracheal immediate intubation and extubation were recorded.Plasma concentrations of cTnT,high sensitive cardiac troponin (hs-cTnT) and high sensitive ereaetive protein (hs-CRP) were detected with central venous blood before anesthesia induction and immediate extubation.Results Compared with group C,the incidences of hypertension,tachycardia,myocardial ischemia,proiosystole and atrial fibrillation were significantly reduced in groups S1 and S2 (P ＜ 0.05);The incidences of bradycardia and hypotension groups were significantly higher in group S1 (P ＜ 0.05).Compared with group S1,the incidences of hypotension,bradycardia,myocardial ischemia were significantly reduced in group S2 (P ＜ 0.05).Compared with group C,plasma concentrations of cTnT,hs-cTnT and hs-CRP were significantly reduced after endotracheal extubation in group S1 and S2 (P ＜ 0.05).Conclusion Myocardial protective effect is better and less risky for patients with coronary artery disease undergoing noncardiac surgery by inhalation of 1.0％ to 2.5％ sevoflurane to maintain BIS between 45 to 55.

Objective:To explore the latent classes of parental feeding behaviors in preschool children, and to examine the relationship between potential types of parental feeding behaviors and parental depression status.Methods:From May to July 2021, parents of preschoolers from eight kindergartens in Shanghai were recruited and investigated.A paper-based questionnaire consisting of the Chinese preschooler’s caregivers’ feeding behavior scale (CPCFBS) and the center for epidemiological studies depression scale (CESD-10) was employed.Finally, a total of 1 006 valid questionnaires were retrieved.Mplus 8.0 and SPSS 26.0 were used for statistical analysis.The latent class analysis was used to identify subgroups of parents based on their feeding practices.Multinomial Logistic regression was used to examine the relevant influencing factors.Results:The feeding behaviors of parental of preschool children could be divided into four potential categories: " high responsiveness and high non-responsiveness type" (24.55%), " low responsiveness and high non-responsiveness type" (27.44%), " high responsiveness and low non-responsiveness type" (28.33%) and " low responsiveness and low non-responsiveness type" (19.68%). The parents with depression status were less likely to be categorized as " high responsiveness and low non-responsiveness type" ( OR=0.386, 95% CI: 0.218-0.684). The parents with older children were more likely to be categorized as " low responsiveness and low non-responsiveness type" ( OR=1.318, 95% CI: 1.039-1.672). Conclusion:The feeding practices of parents of preschool children can be categorized into four latent classes.The parents with depression status are more likely to adopt non-responsive feeding practice than responsive feeding practice.Actively paying attention to and improving the depression status of parents may help the feeder to adopt scientific feeding behavior.

Objective Constructing a risk prediction model of IgA nephropathy proteinuria treated by traditional Chinese medicine based on random survival forest model,Screening prognostic risk factors of IgA nephropathy proteinuria.Methods Collecting retrospectively clinical data of 129 cases diagnosed with IgA nephropathy,randomly divided them into training set(60%)and test set(40%).The risk prediction model of IgA nephropathy proteinuria was constructed in the training set with the random survival forest model,and the prognostic risk factors were screened by VIMP method.The accuracy of risk prediction model was validated in the test set with time-dependent ROC curve(tdROC).Results According to the result of VIMP,the prognostic risk factors for IgA nephropathy proteinuria are in the order of eGFR,hypertension,traditional Chinese medicine,24 hUPRO>1 g,genomo sclerosis ratio,Lee grading,fat,hyperlipidemia,hypertrophymia,hyparmane ledmia,Anemia,age and gender.The eGFR was negatively and non-linearly associated with the risk rate of developing persistent proteinuria.Glomerulosclerosis ratio greater than 0.3 is approximately linearly and positively associated with the risk rate of persistent proteinuria.Conclusion Random survival forest model has good predictive performance in the risk prediction model of IgA nephropathy proteinuria treated by traditional Chinese medicine.This risk model can determine the result of IgA nephropathy treated by traditional Chinese medicine,and which is helpful for clinical follow-up monitoring and formulation of individualized treatment plans.

Objective:To study the safety and treatment outcomes of portal vein embolization (PVE) combined with lenvatinib plus an anti-programmed death-1(PD-1) antibody to treat patients with initially unreasectable hepatocellular carcinoma (uHCC).Methods:This study retrospectively analyzed the data of six patients with uHCC who received first-line combined systemic therapy with lenvatinib plus an anti-PD-1 antibody, and then underwent pre-hepatectomy PVE at the Department of Liver Surgery at Zhongshan Hospital, Fudan University from May 2019 to November 2020. All enrolled patients were males, aged (54.6±6.2) (ranged 46 to 63) years. Tumor response and liver volume were evaluated by medical imagings once every 2 months (±2 weeks) and evaluated using the Response Evaluation Criteria in Solid Tumours (version 1.1). Patients were followed-up by outpatient interviews or by phone calls to record their survival and tumor outcome status.Results:Three of the six enrolled patients had Barcelona Clinic Liver Cancer stage A and three had stage B disease. One patient achieved a partial response and five patients had stable diseases. The mean ± s. d. future liver remnant (FLR) percentage was (29.0±8.9) % before PVE and the combination therapy, and was (41.3±10.8) % before the last evaluation for liver surgery ( t=10.79, P<0.001). Hepatectomy was carried out in five patients, and one patient who failed to develop significant FLR hypertrophy did not undergo hepatectomy. Grade B post-hepatectomy liver failure and major postoperative complications (i.e. pleural effusion requiring additional percutaneous drainage) occurred in one patient. After a median post-operative follow-up of 4.5 (range: 1.0-12.3) months, all five patients were alive and were tumor free. Conclusion:PVE followed by hepatectomy is feasible in a uHCC patients receiving systemic therapy with lenvatinib and an anti-PD-1 antibody.