Objective:To analyze the potential therapeutic targets of Huangqin Tang in treatment of colorectal cancer(CRC)by network pharmacology and molecular docking techniques,and to clarify the related molecular mechanism.Methods:The active component and target dataset for Huangqin Tang were constructed based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP);the CRC-disease related target dataset was built by Databases such as GeneCards,Online Mendelian Inheritance in Man(OMIM),and pharmacogenetics and Pharmacogenomics Knowledge Base(PharmGKB).Drug-disease target intersect,Huangqin Tang herbal formula network,and protein-protein interaction(PPI)networks were built by R software,Cytoscape software,and STRING Database;Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were conducted by R software and Metascape platform;molecular docking validation was performed with AutoDock and PyMOL software to assess the ligand-receptor binding.Results:A total of 136 effective active components of Huangqin Tang were screened,and 242 potential targets were identified for treatment of CRC,including 18 core targets.Five core key targets closely related to CRC,identified through signaling pathway analysis,were protein kinase B1(AKT1),mitogen-activated protein kinase 3(MAPK3),proto-oncogene FOS,tumor protein p53(TP53),and proto-oncogene MYC.The GO functional enrichment analysis results mainly involved various biological processes related to cellular stress responses.The KEGG signaling pathway enrichment analysis results showed that potential targets were highly enriched in the cancer pathway;further analysis on CRC core targets via KEGG signaling pathway revealed involvement primarily in pathways related to endocrine resistance,apoptosis,and epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI)resistance.The molecular docking results showed that the active components of Huangqin Tang,including quercetin,kaempferol,baicalein,7-methoxy-2-methyl isoflavone,and naringenin,were stably docked with AKT1,MAPK3,FOS,TP53,and MYC,and quercetin exhibited the best binding with AKT1.Conclusion:The active components of Huangqin Tang can treat CRC through multi-target and multi-pathway.The core ligand quercetin and AKT1 may exert the therapeutic effect in CRC by regulating the phosphatidylinositol 3-kinase(PI3K)/AKT and mammalian target of rapamycin(mTOR)signaling pathways to influence the cell proliferation,differentiation,and apoptosis processes.

Objective In order to discuss the rationality of clinical use of medication and the strategies of serious adverse reactions(SADR),the reports of SADRs caused by nedaplatin for injection were summarized and analyzed.Methods Methods Serious adverse reactions to all medicines reported to the National Adverse Reaction Monitoring Centre(NARMC)in Tongji Hospital Affiliated to Tongji Medical College,Huazhong University of Science and Technology from January 2012 to December 2021 were collected,and a retrospective analysis of 90 patients among those cases with SADR after nedaplatin injection was carried out.Results The occurrence of SADRs was not related to the gender.In monotherapy with nedaplatin,the rate of serious adverse effects was high with the first use of nedaplatin(74.3%).The incidence of adverse reactions was highest within 30 minutes and 2-14 days,including severe allergic reaction(34.4%)and grade Ⅱ-Ⅳ myelosuppression(51.2%),respectively.Drug withdrawal and symptomatic treatment were often the preferred treatment methods in clinical practice.Conclusion While using nedaplatin as a chemotherapy regimen,especially for the first time,patients should be closely monitored for the occurrence of severe anaphylaxis within 30 minutes and severe bone marrow suppression within 2 weeks.A rescue emergency plan for resuscitation and regular checking of the hemogram should be made to prevent the occurrence of serious adverse reactions.

Objective:To evaluate right atrial (RA) volume and function in patients with hepatitis B cirrhosis by four-dimensional automatic quantitation analysis technique, and to explore its correlation with liver function grading.Methods:Ninety patients with hepatitis B cirrhosis who were clinically confirmed in Henan Provincial People′s Hospital from December 2020 to July 2021 were randomly enrolled as the research subjects. According to Child-Pugh liver function score criteria, the patients were divided into three groups: Child-Pugh A group ( n=31), Child-Pugh B group ( n=31), Child-Pugh C group ( n=28). Another 30 healthy volunteers with gender and age matched at the same period were selected as the control group. The RA maximum volume (RAVmax), RA minimum volume (RAVmin), RA presystolic volume (RAVpreA), RA maximum volume index (RAVImax), RA emptying volume (RAEV), RA ejection fraction (RAEF), RA reservoir longitudinal and circumferential strains (RASr, RASr-c), RA conduit longitudinal and circumferential strains (RAScd, RAScd-c), RA contraction longitudinal and circumferential strains (RASct, RASct-c) were obtained by four-dimensional automatic quantitation analysis technique. Spearman correlation analysis was used to explore the correlation between the volume and strain parameters of right atrium and liver function grading, and the independent correlation factors of RASr-c were analyzed by univariate and multivariate linear regression analyses. Results:Compared with the control group, Child-Pugh A and Child-Pugh B groups, RAVmax, RAVmin, RAVpreA, RAVImax, and RAEV were all increased in Child-Pugh C group (all P<0.05). Compared with control group, the absolute values of RASr, RASct, RASr-c and RASct-c were increased, and the absolute values of RAScd and RAScd-c were decreased in Child-Pugh A group (all P<0.05). Compared with control group, Child-Pugh A and Child-Pugh B groups, the absolute values of RASr, RAScd, RASct, RASr-c, RAScd-c and RASct-c were decreased in the Child-Pugh C group (all P<0.05). Correlation analysis showed that the volume and strain parameters of the right atrium were correlated with liver function grading. RASr-c was independently correlated with E/e, ALB and BNP(β=-0.543, 0.521, and -0.562 respectively, all P<0.05). Conclusions:During the compensatory stage in patients with hepatitis B cirrhosis, the RA functions of reservoir and contractile were increased, but the function of conduit was decreased. With the aggravation of liver cirrhosis, the RA functions of reservoir, conduit and contractile were all decreased. The four-dimensional volume and strain parameters of the right atrium were correlated with Child-Pugh liver function grading, and RASr-c was independently correlated with E/e, ALB and BNP.

Objective:To investigate the change of left atrial volume and function in patients with hypertensive disorders of pregnancy (HDPs) by four-dimensional automatic left atrial quantitative analysis (4D LAQ) and analyze the predictive value of risk stratification.Methods:A total of 60 patients diagnosed with hypertensive disorder of pregnancy in Henan Provincial People′s Hospital from March to December 2021 were randomly enrolled, which were divided into gestational hypertension group (low risk group, n=30) and preeclampsia group (medium and high risk group, n=30) according to the disease development and risk stratification method reported in the literature; another 30 healthy pregnant women matched for age, gestational weeks and body mass index were selected as the control group. Left atrial anteroposterior diameter (LAd), interventricular septum thickness (IVSd), left ventricular end diastolic diameter (LVd), left ventricular ejection fraction (LVEF), left ventricular myocardial mass index (LVMI), peak early diastolic (E) and late diastolic (A) velocities of mitral inflow, and e′ values on the septal and lateral mitral annulus sides were routinely measured to calculate E/A and E/e′ values. Left atrial volume and strain parameters were obtained using 4D LAQ technique, including left atrial minimum volume (LAVmin), left atrial maximum volume (LAVmax), left atrial presystolic volume (LAVpreA), left atrial maximum volume index (LAVImax), left atrial inflation index (LAEI), left atrial stroke volume (LAEV), left atrial fraction (LAEF), longitudinal strain of left atrial reserve, conduit and systolic period (LASr, LAScd, LASct), circumferential strain of left atrial reserve, conduit and systolic period(LASr-c, LAScd-c, LASct-c). The differences among the three groups were compared. Multiple Logistics regression analysis was used to obtain the relevant indicators of risk stratification of HDPs and ROC curves were used for assessment. Results:Compared with the control group, E/e′, LAVmin, LAVpreA, LAScd, and LAScd-c increased, and LAEI, LAEF, LApEF, LASr, and LASr-c decreased in the gestational hypertension group (all P<0.05). Compared with the control group and gestational hypertension group, LAd, IVSd, LVd, LVMI, E/e′ LAVmin, LAVmax, LAVpreA, LAVImax, LAEV, LAScd, and LAScd-c increased, and LVEF, LAEF, LAEI, LApEF, LASr, and LASr-c decreased in the preeclamptic group, and the differences were statistically significant (all P<0.05). The results of multiple Logistics regression showed that LAVmax, LAScd-c and LASr were the indicators relevant to risk stratification of HDPs(β=0.344, 0.216 and -0.249, respectively, all P<0.05). ROC analysis showed when the cut-off value of left atrial strain parameter LASr was 30.5%, the AUC, sensitivity, and specificity were 0.725, 0.58, 0.90, respectively; when the cut-off value of LAVmax was 44.5 ml, the AUC, sensitivity, and specificity were 0.662, 0.80, and 0.56, respectively; and when the cut-off value of LAScd-c was -17.5%, the AUC, sensitivity, and specificity were 0.706, 0.56, and 0.78, respectively. Conclusions:Left atrial remodeling occured in pregnant women with hypertensive disorders, their reserve and conduit function were impaired, and aggravated with the progress of the disease. The four-dimensional parameters LASr, LAVmax, and LAScd-c were relevant indicators for risk stratification of HDPs. In predicting the severity of HDPs, LASr has high diagnostic value and good specificity; LAVmax and LAScd-c can be considered as supplementary parameters to predict the risk stratification of HDPs.

Objective To determine the radiation dose of sensitive organs under different protective methods in lung CT scanning environment, and to explore the best protective scheme of corresponding organs. Methods Annealed thermoluminescence dose elements were placed in the stomach, liver, colon, and thyroid gland of a simulated human body model. The dose effect experiment of protective methods included non-protective group, half lead apron group, and full lead apron group. The dose effect experiment of protective thickness included 0.50 mmpb full lead apron group and 0.35 mmpb full lead apron group. The same exposure conditions of lung CT scan were used in the above experiments. Results Compared with the non-protective group, the exposure dose of the stomach, liver, colon, and thyroid gland increased significantly in the half lead apron group (P < 0.05), and the exposure dose of the thyroid gland and colon decreased significantly in the full lead apron group (P < 0.05). There were no significant differences in the exposure dose of the liver, stomach, and colon in the simulated human body model between the 0.35 mmpb full lead apron group and the 0.50 mmpb full lead apron group. Conclusion For lung CT scan, the protective measure of lead apron may not reduce the exposure dose of subjects. The protective thickness of lead apron does not necessarily have a substantial influence on the exposure dose of human body.

Objective:To investigate the diagnostic value of bronchial arteriography CT (BA-ACT) combined with bronchoscopy (BS) in bronchial Dieulafoy′s disease (BDD), and the role of bronchial artery embolization (BAE) in the treatment of BDD.Methods:Retrospective analysis was made on the clinical data of 5 patients suspected of being BDD treated by BS in Guangzhou First People′s Hospital or Guangzhou Thoracic Hospital from January 2008 to January 2018 due to hemoptysis. Bronchial arteriography (BAG) and BA-ACT were performed during the operation of interventional embolization. BAG rotary acquisition data were post-processed according to BS findings, and BA-ACT reconstruction images of the diseased bronchi and bronchial arteries were obtained. BS reexamination and clinical follow-up observation were carried out after embolization to analyze the effect of embolization.Results:There were one BDD lesion for the five patients respectively, and the BAG lacked characteristic manifestations. Bronchoscopy revealed BDD foci to present as papillary (case 1-case 3), nodular (case 4), or lirellate (case 5) subbronchial submucosal protrusion lesions. On the BA-ACT reconstruction plot, the BDD lesions of papillary, nodular and carination manifested correspondingly as a bronchial artery branches locally " pointed arch" shaped (cases 1-case 4) or " bead-like" (case 5) fold and protruding toward the bronchial lumen. The BDD lesions of the cases 1-case 4 retraction and disappearance after one BAE were observed by BS examination, and no hemoptysis recurrence during the follow-up period (54-91 months). The ridge like BDD lesion of the case 5 remained unchanged after BAE, and hemoptysis recurred at 71 months after the first BAE; the uncollapsed foci were supplied by two collateral vessels that confirmed by second BAG and BA-ACT, and no hemoptysis for 71 months followed up after second BAE.Conclusions:BA-ACT combined with BS enables a locative and qualitative diagnosis of BDD, and BAE is a very effective treatment method for BDD.

Objective:To investigate the prognosis of liver transplantation (LT) elderly recipients and analyze the influencing factors for prognosis.Methods:The retrospective cohort study was conducted. The clinicopathological data of 400 LT recipients who were admitted to three medical centers from January 2015 to June 2020 were collected, including 368 cases in the First Affiliated Hospital of Zhejiang University School of Medicine, 17 cases in the Affiliated Hangzhou First People's Hospital of Zhejiang University School of Medicine and 15 cases in the Affiliated Hospital of Qingdao University. There were 297 males and 103 females, aged from 22 to 75 years, with a median age of 60 years. Of the 400 LT recipients,200 cases aged ≥60 years were divided into elderly recipients (ER) group and 200 cases aged <60 years were divided into non-elderly recipients (NER) group. Reci-pients underwent orthotopic LT or modified piggyback LT. Observation indicators: (1) survival of recipients and grafts for two groups; (2) influencing factors for death of LT recipients; (3) stratification analysis of ER group. Follow-up using the outpatient examination and telephone interview was conducted to detect survival and prognosis of patients up to May 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Kaplan-Meier method was used to calculate survival rates and draw survival curves. Log-Rank test was used for survival analysis. COX regression model was used for univariate and multivariate analyses. Results:(1) Survival of recipients and grafts for two groups: 400 recipients were followed up for 1 day to 71.7 months, with a median follow-up time of 16.3 months. Survival analysis showed that the 1-, 3-year overall survival rates and 1-, 3-year graft survival rates for ER group were 72.70%, 60.66% and 72.70%, 59.64%, respectively, versus 78.84%, 75.48% and 78.84%, 74.22% for NER group, showing significant differences in the overall survival and graft survival between the two groups ( χ2=5.712, 5.681, P<0.05). (2) Influencing factors for death of LT recipients: results of univariate analysis showed that age, score of model for end stage liver disease, Child-Pugh score, cold ischemia time(CIT) of liver donor, hypertension, blood type of recipients and donors, volume of intraoperative blood loss, volume of intraoperative red blood cell transfusion, volume of intraoperative plasma transfusion, volume of intraoperative crystalloid fluid transfusion, the maximum alanine aminotransferase within postoperative 7 days, the maximum aspartate aminotransferase within postoperative 7 days, total bilirubin were related factors for death of LT recipients ( odds ratio=1.026, 1.022, 1.084, 1.070, 1.701, 2.728, 1.000, 1.056, 1.089, 1.000, 1.000, 1.000, 1.003, 95% confidence interval as 1.006-1.045, 1.005-1.040, 1.060-1.170, 1.011-1.132, 1.133-2.554, 1.701-4.374, 1.000-1.001, 1.031-1.082, 1.039-1.142, 1.000-1.003, 1.001-1.004, 1.000-1.002, 1.001-1.004, P<0.05). Results of multivariate analysis showed that age, blood type of recipients and donors, the maximum aspartate aminotransferase within postoperative 7 days, total bilirubin were independent influencing factors for death of LT recipients ( odds ratio=1.022, 2.761, 1.000, 1.007, 95% confidence interval as 1.001-1.044, 1.612-4.727, 1.000-1.001, 1.002-1.012, P<0.05). (3) Stratification analysis of ER group: ① of 200 recipients in ER group, cases with 0 hour≤CIT≤8 hours, 8 hours12 hours were 96, 73, 31 ,respectively. The 1-year overall survival rates for above recipients were 77.46%, 73.33%, 54.07%, and the 3-year overall survival rates were 62.67%, 65.05%, 41.30%. There was a significant difference in the overall survival between the three groups ( χ2=6.708, P<0.05). ② Of 200 recipients in ER group,182 cases were ABO compatible and 18 were ABO incompatible. The 1-year overall survival rates for above recipients were 77.32%, 27.78%, and the 3-year overall survival rates were 64.63%, 22.22%. There was a significant difference in the overall survival between the two groups ( χ2=23.165, P<0.05). Conclusions:The overall survival of ER is inferior to NER. Age, blood type of recipients and donors, the maximum aspartate aminotransferase within postoperative 7 days, total bilirubin are indepen-dent influencing factors for death of LT recipients. Controlling CIT within 12 hours and avoiding ABO incompatible-liver transplantation can significantly improve the prognosis of ER.

Objective: To investigate the clinical results of arthroscopic double-pulley double row suture technique for the treatment of bigger Ideberg Ia glenoid fracture. Methods: From January 2014 to July 2017, data of patients with Ideberg Ia glenoid fracture who were treated by arthroscopic double-pulley double row suture technique were retrospectively analyzed. Totally 24 patients were enrolled of whom 13 were males and 11 were females. The mean age was 50.14±10.60 years (range, 34-67). In those patients, there were 8 cases of glenoid fracture alone, 4 cases of glenoid fracture associated with greater tuberosity fracture, 5 cases of glenoid fracture with rotator cuff tear, 4 cases of glenoid fracture with shoulder anterior dislocation and greater tuberosity fracture, 2 cases of glenoid fracture with shoulder anterior dislocation and rotator cuff tear, and 1 case of shoulder anterior dislocation with ipsilateral distal radius fracture. The fragment accounts for 28.91±5.35% (range, 25.1%-38.5%) of the glenoid articular surface. According to the size of the fragment, one medial row anchor was used to implant at the medial edge of the fracture bed of the anterior edge of the glenoid; two to four lateral row suture anchors were used to implant at the margin of the glenoid joint surface sequentially from low level to higher level, and simplified double-pulley technique was finally used to fix the fragment. The situation of fracture reduction and healing and the post-operative complications were evaluated. The Constant-Murley, DASH and VAS were also recorded. Results: Satisfactory fracture reduction and fixation were achieved in all 24 patients. The mean follow-up time was 19.5 months (range, 12-36). Mean VAS was 0.8±0.8 (range, 0-2). The range of motion at the latest follow-up was: anterior flexion 145°-180° (mean, 161.00°±5.77°), external rotation at the side 35°-60° (mean, 46.43°±6.63°), internal rotation L₃-T₁₀ level. The mean Constant-Murley score was 88.1±3.7 (range, 81-93), and mean DASH score was 8.4±4.7 (range, 0-40.4). All cases except one showed no dislocation or disability of the shoulder. The CT scans showed: 19 cases of which the step-off of articular surface was less than 2 mm; 4 cases of which the step-off was between 2 mm to 4 mm and 1 case of which the step-off was more than 4 mm. No severe osteoarthritis was identified at the latest follow-up, and only 1 patient at the age of 67 showed slight osteoarthritis. Two patients with shoulder anterior dislocation and rotator cuff tear committed significant restricted shoulder range of motion. Conclusion The arthroscopic simplified double-pulley double row suture technique was identified safe, effective and reliable for treating the bigger Ideberg Ia glenoid fracture. The technique is able to provide clear visulization of the fracture and achieve excellent clinical results.

OBJECTIVES: To establish an electrophysiological model of alcoholic cardiomyopathy by inducing pluripotent stem cells (iPSCs) to differentiate into cardiomyocytes (iPSC-CM) in vitro. METHODS: The human iPSC were expanded in vitro and differentiated into iPSC-CM. The iPSC-CM were divided into a blank control group, an alcoholic experiment group (according to the concentration of alcoholic, the alcoholic experiment was also divided into many subgroups), and a KN93 treatment group. Then the efficiency of iPSC differentiated to iPSC-CM was detected by immunofluorescence, the function of iPSC-CM was detected by cell counting kit-8 (CCK8) assay and lactate dehydrogenase (LDH) activity assay kit. The electrophysiological activity of iPSC-CM was monitored by real time cellular analysis (RTCA), the injury of iPSC-CM caused by alcohol was further verified by the mitochondrial membrane potential fluorescence probe JC-1 staining combined with RTCA analysis. RESULTS: Compared with the blank control group, the different doses (25, 50, 100, 150, 200, 250, 300 mmol/L) of alcohol could significantly inhibit the proliferation of iPSC-CM in a dose-dependent manner (all <0.05). Compared with the blank control group, the activity of iPSC-CM was significantly reduced by 100 mmol/L alcohol, resulting in the increase of LDH release, the decrease of mitochondrial membrane potential, the amplitude and beating rate (all <0.05). Compared with the 100 mg/mL alcoholic experiment group, the KN93 treatment group significantly alleviated the damage of alcohol to iPSC-CM by blocking the necrotic apoptotic pathway, resulting in the decrease of LDH release, the increase of mitochondrial membrane potential, the amplitude and beating rate (all <0.05). CONCLUSIONS The electrophysiological model of alcoholic cardiomyopathy based on the differentiation of cardiomyocytes are successfully established, which can be used to study the electrophysiological activity and the molecular mechanism for relevant diseases, and it may provide a more reasonable and effective research tool for drug screening and clinical study.
Cardiomyopathy, Alcoholic ; Cell Differentiation ; Electrophysiological Phenomena ; Humans ; Induced Pluripotent Stem Cells ; Myocytes, Cardiac

Objective:To explore the clinical prognosis of early endarteritis (within 2 weeks) and late endarteritis (after 2 weeks) after renal transplantation.Methods:A total of 81 cases with higher creatinineand receiving renal biopsy after renal transplantation were recruited from September 2001 to December 2014. They were divided into early endarteritis group (n=43) and late endarteritis group (n=38). Baseline profiles, serum creatine, glomerular filtration rate (GFR) before and after treatment, steroid resistance, reversal rate, graft loss and survival rate were analyzed for two groups.Results:Early endarteritis group showed worse serum creatine and GFR than late endarteritis group before rejection. Early endarteritis group had a higher rate of treatment with steroid plus antibody (86 %) than that of late endarteritis group (86 %vs.18.6 %, P<0.05). No significant inter-group difference existed in graft loss (23.3 % vs.10.5 %, P=0.131). The survival curve of transplanted kidney showed no significant inter-group difference insurvival time. Conclusions:The status of patients with early simple endothelitis is significantly worse than that of those with late simple endothelitis. However, after active treatments, the prognosis of patients with early simple endothelitis is not inferior to that of those with late simple endothelitis.