Objective To explore the intrinsic steady-state electrophysiological properties of mouse heart under physiological conditions by high-resolution quantitative analysis.Methods Twenty-two young adult C57BL/6 mice with a 1:1 male-to-female ratio were used.The limbs of the mice were fixed without anesthesia,and electrocardiographic waveforms,including characteristic P-waves,R-waves,and ST-waves,were recorded using a sensitive 12-lead electrophysiological recorder(ECGsqa)under spontaneous breathing.LabScribe software was used to extract and quantify high-resolution time course and amplitude parameters within a single cardiac cycle from the V3 precordial lead.Pearson correlation test combined with simple linear regression was used to generate a scatter plot of ECG parameter fitting.The common and unique correlation parameters were separately identified by joint associations for profiling the quantitative association network.Results ECGsqa analysis identified and quantified 14 characteristic ECG parameters,28.6%of which showed statistical differences between the groups.Compared to male mice,female mice exhibited higher amplitudes and velocities of R and ST waves.Among the 51 association pairs identified in primary association analysis,47.1%were positively correlated,including shared(29.2%),male-specific(29.2%),and female-specific(41.7%)association groups.Second-order clustering of the association pairs revealed that the amplitude-rate association pairs of each waveform voltage in both male and female mouse hearts were strongly correlated.The male mice showed an atrioventricular interconnection pattern,while the female mice showed a unique atrial conduction system quality dependence.The distribution network characteristics of the association groups showed that sex-specific and common correlation sets formed a certain series pattern.Conclusion We discovered a novel intrinsic correlation network of cardiac electrophysiological traits in male and female mice,which reveals the key internal quantitative characteristics and gender difference of both atrial and ventricular conduction systems.

Objective:To investigate the predictive ability of Glypican-3 (GPC3) positive hepatocellular carcinoma based on the hepatobiliary specific contrast agent gadoxetate disodium enhancement of the liver imaging reporting and data system version 2018 (LI-RADS v2018) imaging features, and to assess the relevant clinical imaging features for postoperative recurrence in GPC3 positive HCC patients.Methods:This study was a cohort study. A total of 122 hepatocellular carcinoma patients who underwent gadoxetate disodium enhanced MRI examination with hepatic tumor resection in Henan Provincial People′s Hospital from January 2017 to December 2021 were retrospectively collected, including 96 GPC3 positive and 26 GPC3 negative patients. The imaging features defined by LI-RADS v2018 of HCC lesions were analyzed. Patients were followed up for 40 months to determine recurrence free survival (RFS). The logistic regression was used to analyze the risk factors of GPC3 positivity. An imaging model, and a clinical-imaging model which combined the patient′s alpha-fetoprotein levels were constructed. The efficacy of the model for predicting GPC3 positivity was assessed using receiver operating characteristic curves. Kaplan-Meier method was used to draw the survival curve, and the log-rank test was used to compare the RFS between GPC3 positive and negative patients. Risk factors affecting the recurrence of GPC3 positive HCC were assessed by Cox regression.Results:The results of logistic multivariate regression analysis confirmed that rim enhancement ( OR=5.685, 95% CI 1.229-26.287, P=0.026) and irregular tumor margin at hepatobiliary phase ( OR=4.431, 95% CI 1.684-11.663, P=0.003) were independent risk factors for GPC3 positive HCC. The area under the curve for predicting GPC3 positivity was 0.745 (95% CI 0.636-0.854) for the imaging model and 0.776 (95% CI 0.677-0.876) for the clinical-imaging model. The mean RFS in the GPC3 positive group was 22 months, and it was 32 months in the negative group. There was a statistically significant difference in RFS between the two groups ( χ2=5.15, P=0.023). The multivariate Cox regression analysis showed that the arterial rim enhancement ( HR=5.460, 95% CI 1.966-15.162, P=0.001), microvascular invasion ( HR=2.402, 95% CI 1.210-4.769, P=0.012), portal vein tumor thrombus ( HR=3.226, 95% CI 1.114-9.344, P=0.031) were independent risk factors for recurrence after hepatic tumor resection for GPC3-positive HCC. Conclusions:A model based on the LI-RADS v2018 imaging features of hepatobiliary specific contrast agent gadoxetate disodium enhancement can effectively predict GPC3 positive HCC. The arterial rim enhancement, microvascular invasion and portal vein tumor thrombus are independent risk factors for postoperative recurrence of GPC3 positive HCC.

Objective To explore the intrinsic steady-state electrophysiological properties of mouse heart under physiological conditions by high-resolution quantitative analysis.Methods Twenty-two young adult C57BL/6 mice with a 1:1 male-to-female ratio were used.The limbs of the mice were fixed without anesthesia,and electrocardiographic waveforms,including characteristic P-waves,R-waves,and ST-waves,were recorded using a sensitive 12-lead electrophysiological recorder(ECGsqa)under spontaneous breathing.LabScribe software was used to extract and quantify high-resolution time course and amplitude parameters within a single cardiac cycle from the V3 precordial lead.Pearson correlation test combined with simple linear regression was used to generate a scatter plot of ECG parameter fitting.The common and unique correlation parameters were separately identified by joint associations for profiling the quantitative association network.Results ECGsqa analysis identified and quantified 14 characteristic ECG parameters,28.6%of which showed statistical differences between the groups.Compared to male mice,female mice exhibited higher amplitudes and velocities of R and ST waves.Among the 51 association pairs identified in primary association analysis,47.1%were positively correlated,including shared(29.2%),male-specific(29.2%),and female-specific(41.7%)association groups.Second-order clustering of the association pairs revealed that the amplitude-rate association pairs of each waveform voltage in both male and female mouse hearts were strongly correlated.The male mice showed an atrioventricular interconnection pattern,while the female mice showed a unique atrial conduction system quality dependence.The distribution network characteristics of the association groups showed that sex-specific and common correlation sets formed a certain series pattern.Conclusion We discovered a novel intrinsic correlation network of cardiac electrophysiological traits in male and female mice,which reveals the key internal quantitative characteristics and gender difference of both atrial and ventricular conduction systems.

Objective:To investigate the efficacy and safety of radium-223 in combination with new-generation hormonal agents in patients with bone metastases of prostate cancer.Methods:The clinical data of 17 patients (12 from the First Affiliated Hospital of Airforce Military Medical University and 5 from Xi'an International Medical Center Hospital) with metastatic castration-resistant prostate cancer(mCRPC) treated by radium-223 combined with new-generation hormonal agents from January 2021 to June 2022 were retrospectively analyzed. In all cases, the average age was (73.3±8.5) years old. Before treatment, the median prostate-specific antigen (PSA) was 15.7 (3.2, 36.5) ng/ml, the median alkaline phosphatase (ALP) was 131.5 (79.0, 430.7) U/L. All patients had ≥ 2 bone metastases but no visceral or lymph node metastases. The median number of bone scan lesions was 10(8, 15). Bone pain symptom was present in 16(94.1%) patients. There were 9 cases (52.9%) with Eastern Cooperative Oncology Group (ECOG) score of ≥2, 1 case (5.9%) with ECOG score of 1 and 6 cases (35.2%) with ECOG score of 0. All patients were treated with radium-223 (55 kBq/kg, injected every 4 weeks for a maximum of 6 cycles), of which 5 patients were combined with enzalutamide, 8 patients combined with apatamide and 4 patients combined with bicalutamide. PSA response (PSA decreased by ≥30% from baseline and maintained for at least 1 month), ALP response (ALP decreased by ≥30% from baseline and maintained for at least 1 month) and pain relief rates were analyzed. Imaging evaluation was performed before and after treatment to calculate the objective response rate of metastases. The incidence of treatment-related adverse effects and skeletal related event (SRE) were also recorded.Results:Eleven patients completed 6 courses, 3 patients completed 5 courses and 3 patients completed ≥4 courses. The median ALP after 1 month of last treatment was 83.2 (51.5, 126.5) U/L, which was significantly decreased than baseline. 12 patients (70.6%) showed an ALP response and the other 5 (29.4%) showed varying degrees of ALP elevation. PSA response was observed in 4 patients (23.5%), of which 2 (11.8%) had a continuous decrease and 2 (11.8%) had a late-stage increase in PSA. Pain relief was relieved in 15 cases (88.2%) during treatment, 1 case (5.9%) had worsening pain due to disease progression and 1 case (5.9%) had no change during treatment. The ECOG score decreased in 15 (88.2%) patients. The median number of bone metastases in patients decreased to 5 (4, 9). One patient (5.9%) had complete remission during treatment, 11 patients (64.7%) had a partial response, 4 patients (23.5%) were stable, and 1 (5.9%) showed imaging progression after 4 months of treatment. The overall objective remission response rate was 70.5% (12/17). Treatment-related hematologic adverse effects included anemia (1 case, 5.9%, grade 3), thrombocytopenia (1 case, 5.9%, grade 3) and leukopenia (1 case, 5.9%, grade 2). Non-hematologic adverse effects included fatigue (3 cases, 17.6%, 2 cases in grade 1, 1 case in grade 2), gastrointestinal bleeding (1 case, 5.9%, grade 3), diarrhea (1 case, 5.9%, grade 2) and fever (1 case, 5.9%, grade 1). Patients with grades 1 to 2 relieved with symptomatic management. Three cases (17.6%) were discontinued due to intolerance of grade 3 adverse reactions and 1 case (5.9%) terminated on its own. There was no SRE during treatment and follow-up.Conclusions:Radium-223 combined with New-generation hormonal agents has a high objective remission rate in patients with mCRPC, which could provide pain relief and improve quality of life. The incidence of adverse reactions was low and well tolerated.

Objective:To evaluate the short-term efficacy of split liver transplantation (SLT) in patients with acute-on-chronic liver failure (ACLF).Methods:The clinical data of 9 ACLF patients receiving SLT in our center from Mar 2021 to May 2022 were retrospectively analyzed to evaluate its safety and efficacy.Results:The preoperative APASL ACLF Research consortium (AARC) score of the 9 ACLF patients was 8 points in 1 case, 9 points in 3 cases, 10 points in 3 cases, 11 points in 1 case and 12 points in 1 case, 7 cases were in AARC-ACLF grade 2, and 2 cases in grade 3.In-situ liver splitting was performed in 9 deceased donors, including 4 classical split cases, 5 full size split cases. Among these 9 ACLF patients, 2 received left half liver transplantation, 3 received right half liver transplantation, and 4 received extended right lobe liver transplantation. After transplantation, all 9 recipients were discharged fully recovered, 1 case developed Clavien grade Ⅳa complication and 2 cases developed Clavien grade Ⅲb complication.After SLT treatment the median postoperative hospital stay was 27 days, the 1-year survival rate was 100%, and the organ survival rate was 88.9%.Conclusion:Split liver transplantation is a safe and feasible treatment method for ACLF patients.

Objective    To compare the outcomes following emergency surgery or conservative treatment for patients with acute type A aortic intramural hematoma (IMH). Methods    Clinical data of consecutive patients diagnosed with acute type A aortic IMH in our hospital from September 2014 to December 2018 were retrospectively analyzed. The patients who met our surgical indications received surgery (an operation group) and other patients received strict conservative treatment (a conservative treatment group). Results    Finally 127 patients were enrolled, including 112 males and 15 females with an average age of 53.6±13.0 years. Of 127 patients, 85 (66.9%) patients accepted emergency surgery and 42 (33.1%) patients accepted strict conservative treatment. There was no difference between the two groups in early mortality or complications (P>0.05). The 5-year survival rate was 90.4% in the operation group and 74.3% in the conservative treatment group (P=0.010). A maximum aortic diameter in the ascending aorta and aortic arch≥45 mm and maximum thickness of IMH in the same section≥8 mm were risk factors for IMH-related death in patients undergoing conservative treatment (P<0.001). Conclusion    The mortality associated with emergency surgery for patients with acute type A aortic IMH is satisfactory. In clinical centers with well-established surgical techniques and postoperative management, emergency surgical treatment may provide a better outcome than conservative treatment for patients with acute type A aortic IMH.

OBJECTIVE To op timize the i ntegrated technology of producing area processing and decoction pieces processing of Curcuma longa （hereinafter refer to “integrated technology ”）. METHODS The content of ethanol-soluble extract in C. longa was determined by hot leaching method ；the contents of curcumin ，demethoxycurcumin and bisdemethoxycurcumin were determined by high performance liquid chromatography. On the basis of identification of producing area processing technology ， Using overall desirability （OD） value of the contents of ethanol-soluble extract ， curcumin， demethoxycurcumin and bisdemethoxycurcumin as evaluation indexes ，moisture content ，slice thickness and drying temperature as factors ，the integrated technology of C. longa was optimized by single factor tests combined with central composite design-response surface method ，and the validation tests were conducted. At the same time ，prepared product was compared with traditional decoction pieces prepared according to 2020 edition of Chinese Pharmacopoeia （part Ⅰ）. RESULTS The best integrated technology was that the fresh C. longa was boiled in boiling water for 5 min，dried at 50 ℃ to 40％ water content ，cut into 2 mm thin slices ，and dried at 50 ℃ until moisture content not exceeding 15.0％. After validation ，The deviation between the average OD value （0.811 3，RSD＝2.13％） and the predicted value （0.848 1）of the contents of ethanol-soluble extract ，curcumin，demethoxycurcumin and bisdemethoxycurcumin was 4.34％. OD value of the contents of ethanol-soluble extract ，curcumin，demethoxycurcumin and bisdemethoxycurcumin in decoction pieces prepared by integrated technology were all higher than those prepared by traditional technology. CONCLUSIONS The process optimized in this study is simple ，stable and feasible.

Objective:To evaluate the value of quantitative analysis of the relative signal intensity (SI) of liver gadolinium disodium enhanced MRI in the grading of liver fibrosis.Methods:From January 2018 to October 2020, the relevant data of 131 patients who underwent gadoxetate disodium enhanced MRI examination were retrospectively analyzed in Henan Provincial People′s Hospital. All patients had histopathological results. According to the Laennec grading system of liver fibrosis, the patients were classified in F0-F1 (27 cases), F2 (19 cases), F3 (17 cases) and F4 (68 cases). The signal intensity of the liver, erector spinae and spleen were measured before and after the enhancement; and 5 post-contrast relative SI parameters were calculated, including the relative enhancement (RE), liver-to-muscle contrast ratio (LMC), liver-to-spleen contrast ratio (LSC), LMC increase rate, LSC increase rate. The differences of 5 post-contrast relative SI parameters among the different fibrosis grades were compared using one-way analysis of variance. The receiver operating characteristic (ROC) curves were drawn to evaluate the diagnostic efficacy of 5 post-contrast relative SI parameters in the diagnosis of clinically significant liver fibrosis (F2-F4), advanced liver fibrosis (F3-F4) and liver cirrhosis (F4).Results:The differences of RE, LMC, LSC, LMC increase rate, LSC increase rate among different liver fibrosis grades were statistically significant (all P<0.001). With the increasing of the degree of liver fibrosis, the RE, LMC increase rate and LSC increase rate showed decreased. ROC results showed that the area under the curve (AUC) of RE, LMC increase rate, LSC increase rate in diagnosing liver fibrosis in all levels were greater than those of LMC and LSC. The AUC values of RE, LMC increase rate, LSC increase rate in the diagnosis of significant fibrosis (F2-F4) were 0.89, 0.86, 0.83, with the sensitivity as 81.7%, 71.2%, 81.7%, and the specificity as 96.3%, 85.2%, and 74.1%, respectively. The AUC values of RE, LMC increase rate, LSC increase rate in the diagnosis of advanced liver fibrosis (F3-F4) were 0.93, 0.88, 0.86, with the sensitivity as 84.7%, 72.9%, 91.8%, and the specificity as 91.3%, 87.0 %, 71.7%; and the AUC values for diagnosing liver cirrhosis (F4) were 0.92, 0.86, 0.85, with the sensitivity as 82.4%, 76.5%, 92.7%, and the specificity as 88.9%, 81.0%, 65.1%, respectively. Conclusion:Gadoxetate disodium enhanced MRI relative SI parameters including RE, LMC increase rate and LSC increase rate might be used as a useful imaging marker in liver fibrosis grading.

Objective:To investigate the clinical outcomes of patients with intrahepatic cholangiocarcinoma (ICC) undergoing surgical resection.Methods:Patients who undergoing radical surgical resection for ICC from Jan 2015 to Apr 2021 at the Department of General Surgery, the First Affiliated Hospital of Anhui Medical University were included in this retrospective cohort study.Results:There were 67 patients in the final analysis, The median follow-up duration was 14 months (range: 1-60 months). Firty three patients (79.1%) had tumor recurrence, 52 patients (77.6%) died, Among them, 49 patients (73.1%) died from tumor recurrence. The 1-、2-、and 3-year accumulated disease-free and overall survival rate were 35.6%, 19.6%, 16.8% and 53.7%, 32.4%, 20.8%. respectively. The overall survival rate of the group without microvascular invasion was significantly better than those of the group with microvascular invasion ( χ2=5.916, P=0.015). CA19-9≥1 000 U/ml was the only independent risk factor for the disease-free survival. CA19-9≥1 000 U/ml、blood loss≥600 ml、microvascular invasion and tumor recurrence were the independent risk factors for the overall survival. Conclusion:For ICC patients with single tumor, when the tumor diameter is less than 5 cm and has no microvascular invasion, surgical resection is recommended, and a satisfactory prognosis could be achieved.

Objective:To identify the causative genes of sporadic thoracic aortic aneurysm or dissection (TAAD) and their correlation with clinical phenotype in the southern Chinese.Methods:We analyzed 11 core genes of TAAD probands without specific family history of 226 cases by next-generation sequencing technology, and performed sanger sequencing for their close relatives. Clinical data of each patient, including age of onset, syndromic phenotypes, involvement of aortic root, aortic maximum diameter and D-dimer were collected. And statistical software SPSS was used to evaluate the correlation between clinical phenotypes and gene mutations.Results:A total of 106 variants were detected in 226 probands with gene-positive frequency of 44.69%, consist of 16 pathogenic (P) variants, 18 likely pathogenic (LP) variants and 71 variants of uncertain significance (VUS). More than half of the mutations were from the non-syndromic TAAD, in which the FBN1 still was the most common causative gene. Earlier age of onset, an increase of women, larger diameter of aorta, Stanford B dissection and severe aortic regurgitation were likely to occur on carriers of P/LP, while thoracic aortic aneurysm occurs on carriers of VUS. Phenotype of both syndrome and dissection with aneurysm could increase the likelihood of carrying gene mutation, but D-dimer and involvement of aortic root couldn’t.Conclusion:Patients with sporadic aortic diseases in southern China have significant genetic heterogeneity and specific correlation between their clinical phenotype and gene mutation, especially in non-syndromic population. Earlier age of onset in carriers of FBN1 or ACTA2 genes, and larger maximum diameters of aorta in carrier of P/LP.