1.Mechanism of effect of rosiglitazone on pancreatic cancer in diabetic mice based on impact of PPARy on glucose transport and metabolism
Rui-Ping HU ; Li-Feng SHANG ; He-Jing WANG ; Hong-Xia CHE ; Ming-Liang WANG ; Huan YANG ; Yuan-Yuan JIN ; Fei-Fei ZHANG ; Jian-Ling ZHANG
Chinese Pharmacological Bulletin 2024;40(7):1325-1334
Aim To explore the mechanism of the effect of rosiglitazone(Rsg)on the pancreatic cancer in diabetic mice based on the impact of PPARγ on glu-cose transport and metabolism.Methods A high-fat and high sugar diet combined with STZ was used to construct T2DM model;T2DM mice and normal mice were subcutaneously injected with PANC02 cells to construct a transplanted tumor model.T2DM trans-planted tumor mice and normal transplanted tumor mice were divided into the following groups:Rsg,PPARy inhibitor(PIN-2),rosiglitazone+PPARγ in-hibitor(Rsg+PIN-2),and normal transplanted tumor mice(NDM)and T2DM transplanted tumor mice(DM)were used as control groups,respectively.Tis-sue samples were collected after intervention.Tissue pathological changes were observed by HE staining.The expressions of Ki67 and PCNA proteins were de-tected by immunohistochemistry.Cell apoptosis was detected by TUNEL assay.The expression of PPARγwas detected by immunofluorescence.The expressions of Glucokinase,GLUT2,Nkx6.1,PDX-1RT-PCR were determined by Western blot.Results Rsg could significantly reduce the tumor mass,pathological chan-ges,Ki67 and PCNA expression of transplanted tumors(P<0.05),increase cell apoptosis and the expression of PPARγ,Glucokinase,GLUT2,Nkx6.1,PDX-1 proteins in NDM and DM mice(P<0.05).PIN-2 could reverse the indicator changes caused by Rsg in NDM and DM mice.However,compared with NDM mice,the above related indicators of the DM group mice were more sensitive to Rsg and PIN-2.Conclu-sions Compared to non-diabetic pancreatic cancer,rosiglitazone can more sensitively inhibit the prolifera-tion of pancreatic cancer with T2DM,induce apopto-sis,and reprogram the metabolism of pancreatic cancer with T2DM by activating PPA Rγ and altering the ex-pression of glucose and lipid metabolism genes,there-by exerting an anti-cancer effect.
2.Molecular epidemiological analysis of group A rotavirus in diarrhea cases in children under 5 years of age in Guangdong Province,2021-2022
Cai-Xia LI ; Chang ZHANG ; Wei ZHANG ; Han-Ri ZENG ; Huan-Ying ZHENG ; Bo-Sheng LI ; Bi-Xia KE
Chinese Journal of Zoonoses 2024;40(9):834-840
This study investigated the epidemiological and genotypic characteristics of group A rotavirus(RVA)in children under 5 years of age with diarrhea at a viral diarrhea surveillance sentinel hospital in Guangdong Province from 2021 to 2022,to provide a basis for RVA prevention and control.A total of 1 858 fecal samples from children under 5 years of age with diarrhea in 2021-2022 were collected.Rotavirus antigen was detected with ELISA,and positive samples were further sequenced and categorized.Among the 1 858 samples,156 were RVA positive.The positivity rates in boys and girls were 8.76%and 7.87%,respectively.Significant differences were observed in the detection rates of RVA infection among age groups.The rate of RVA infection increased gradually from December to April of the following year.In 2021,the main endemic strains of RVA in the Guangdong region were of the G9P[8]subtype,and the rare G8P[8]subtype increased in China.In 2022,the G8P[8]subtype surpassed the G9P[8]subtype for the first time.In cases of diarrhea in infants younger than 5 years in Guangdong Province from 2021 to 2022,the RVA genotypes were diverse,the G9P[8]genotype significantly decreased,and the G8P[8]subtype became a dominant genotype.Continuous RVA genotype monitoring remains necessary to assess the risk of RVA-related disea-ses.
3.Clinical Observation on Haploid Hematopoietic Stem Cells Combined with Umbilical Cord Blood Double Transplantation for Aplastic Anaemia in Children
Huan-Jun LIU ; Xing-Hua CHEN ; Wen-Bang ZHANG ; Shu-Xia GUO
Journal of Experimental Hematology 2024;32(3):890-895
Objective:To explore the efficacy and safety of haploidentical hematopoietic stem cell transplantation combined with umbilical cord blood infusion for the treatment of aplastic anaemia in children.Methods:Nine cases of children with aplastic anaemia treated with umbilical cord blood combined with haploidentical hematopoietic stem cell transplantation at the People's Hospital of Henan University of Chinese Medicine from January 1,2021 to September 15,2023 with a median age of 11(2-13)years and a median follow up of 18(7.5-21)months were included,and the clinical data were retrospectively analyzed.Hematopoiesis reconstitution,the incidence of graft-versus-host disease(GVHD),infections and survival of the patients were analyzed.Results:All 9 children were successfully implanted.The median time to neutrophil and platelet implantation was 11.11±1.27 d and 12.44±3.36 d,respectively.One case developed acute gastrointestinal GVHD of degree I,which was improved after treatment,and the patient developed superficial gastritis and chronic gastrointestinal GVHD at a later stage,which is currently under clinical follow-up.Acute GVHD of Ⅱ-Ⅳ degree was 0%.Hemorrhagic cystitis in 3 cases,CMV infection in 5 cases and bacterial and fungal infections in 5 cases improved with symptomatic treatment.All 9 children demonstrated complete donor chimerism within 1 month after transplantation,at two years of follow-up,all nine children survived without recurrence or development of grade Ⅱ-Ⅳ GVHD,and there were no children with transplant-related deaths.Conclusion:Haploidentical hematopoietic stem cell transplantation combined with umbilical cord blood transfusion for aplastic anaemia in children has a low incidence and mild degree of GVHD,with significant efficacy,and can be used as a therapeutic option for children without an HLA full donor chimeric match.
4.SEPT 12 in male infertility:Advances in studies
Hai-Xia CHEN ; Jing ZHANG ; Xiao-Huan MU ; Wen-Yan TIAN
National Journal of Andrology 2024;30(11):1030-1035
SEPT1 2,as a member of the septin gene family,is preferentially expressed in the adult male testis and plays an im-portant role in the spermatogenesis and maturation of sperm.It is also essential for the maintenance of the structural integrity of the sperm tail.SEPT12 is closely related to sperm morphological abnormality,and its mutation leads to decreased fertility or infertility of males.This review presents an overview of the advances in and affords a prospect of the studies on the structure and biological functions of SEPT12 and the impact of its mutation on male fertility.
5.Risk factors of postoperative mortality of femoral neck fractures in elderly patients and construction of a nomogram predictive model
Zhipeng LI ; Dawei HUAN ; Zhaofeng YUAN ; Yue QIU ; Chao ZHANG ; Tianwei XIA ; Jirong SHEN
Chinese Journal of Tissue Engineering Research 2024;28(21):3361-3366
BACKGROUND:With a gradually aging population,improving the ability to screen for the risk of death after arthroplasty and implementing timely personalized intervention programs for the increasing number of elderly patients with femoral neck fractures is key to improving the postoperative status of patients and prolonging survival expectations. OBJECTIVE:To investigate the risk factors for postoperative mortality in elderly patients with femoral neck fractures and to construct a nomogram predictive model to predict their mortality risk. METHODS:The study was conducted on 155 elderly patients(≥65 years old)who underwent arthroplasty for femoral neck fracture from January 2016 to January 2021,and 147 patients who met the inclusion criteria were analyzed to collect clinical data that may affect the patients'postoperative mortality.Single-factor and multi-factor Cox regression analyses were successively used to screen independent risk factors associated with postoperative mortality.The column line graph model was constructed and validated using Rstudio software. RESULTS AND CONCLUSION:(1)Age,frailty(age-adjusted Charlson comorbidities score),preoperative activity status,osteoporosis,and postoperative serum albumin level were five independent risk factors for postoperative mortality in elderly patients with femoral neck fractures(P<0.05).(2)The nomogram predictive model was constructed based on the results of multifactorial analysis,with a consistency index of 0.819(95%CI:0.771-0.868).Receiver operating characteristic curve analysis showed that the area under curve for 1-year and 3-year survival prediction was 0.8543 and 0.7263,respectively,indicating that the nomogram predictive model has good discriminatory and predictive power;calibration curve and decision curve analysis also showed good model discriminative power and clinical utility value.(3)The constructed nomogram predictive model has good diagnostic efficacy and accuracy,and can effectively assess the risk of postoperative death of patients.
6.Effect of Esketamine on Early Negative Postoperative Behavioural Occurrence After Pediatric Concealed Penis Correction
Huan ZHANG ; Yingying SUN ; Yin XIA ; Yuanhai LI
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(5):835-843
[Objective]To investigate the effect of esketamine pretreatment on early negative postoperative behavioural occurrence after pediatric concealed penis correction.[Methods]A total of 88 children,aged 4-10 years old,of American Society of Anesthesiologists physical status Ⅰ-Ⅱ,undergoing pediatric cryptorchid penis correction operation within 1 hour,were randomly divided into the esketamine group(Group E,n=44)and the control group(Group C,n=44)according to the computer-generated random numeral order.Esketamine was infused intravenously at a dose of 0.5 mg/kg 20 minutes before entering the operating room in Group E,while equal volume of normal saline was given instead of esketamine in group C.General anesthesia with laryngeal mask and inhalation anesthesia was used in both groups.The anxiety level of children was evaluated by modified Yale Preoperative Anxiety Scale(m-YPAS)on the day before surgery and before entering operating room on the day of the operation.The induction compliance level of children was evaluated by the Induction Compliance Checklist(ICC).Heart rate(HR)and mean arterial pressure(MAP)were recorded before the induction of anesthesia(T0),immediately after the induction(T1),the beginning of the operation(T2),the time of admission to the PACU(T3),10 min after the PACU(T4),and before discharge from PACU(T5).Paediatric Anaesthesia Awakening Delirium Scale(PAED)and Pain Behavioural Assessment Scale(FLACC)scores were performed during awakening.A volume of 3 mL of peripheral venous blood was collected on the first preoperative day as well as the first postoperative day,and the levels of monocyte chemotactic protein 1(MCP-1),cortisol and epinephrine were measured.The Postoperative Behavioural Questionnaire(PHBQ)questionnaire was recorded on postoperative days 3 and 7 for all children.[Results]The incidence of NPOBCs on postoperative days 3 and 7 was significantly lower in Group E compared with that of Group C(31.8%vs.63.6%,P<0.05;18.2%vs.40.9%,P<0.05).The incidence of separation anxiety,sleep anxiety,and eating disorders in the PHBQ on postoperative day 3 was significantly lower in Group E than in Group C.The difference was statistically significant(P<0.05);there was no statistically significant difference between the two groups when comparing the incidence of overall anxiety,aggression,and apathetic withdrawal(P>0.05).On postoperative day 7,the incidence of all indicators in the PHBQ was not statistically different between the 2 groups(P>0.05).Compared with Group C,postoperative MCP-1 was significantly lower in Group E,and the difference was statistically significant(P<0.05);whereas for epinephrine and cortisol levels,there was no statistically significant difference between the 2 groups(P>0.05).Multivariable logistic regression analysis suggested that the possible risk factors for NPOBCs after pediatric concealed penis correction included the m-YPAS score[OR=1.152,95%CI(1.083,1.226);P=0.000],and the use of esketamine[OR=0.223,95%CI(0.062,0.803);P=0.022].The AUC under the ROC curve of m-YPAS and the use of esketamine as two predictors of the occurrence of NPOBCs were 0.918[P<0.001,95%CI(0.849,0.988)]and 0.659[P=0.010,95%CI(0.544,0.774)],respectively.There was no statistically significant difference in PAED scores and FLACC scores between the two groups in the PACU(P>0.05).[Conclusion]Esketamine pretreatment can reduce the incidence of NPOBCs in children undergoing concealed penis correction,which may be associated with a reduction in postoperative MCP-1,without an increase in perioperative adverse events and with a high safety profile.
7.The Regulatory Function of ADAR1-mediated RNA Editing in Hematological Malignancies
Xing-Yu WAN ; Huan-Ping GUO ; Rui-Hao HUANG ; Xiao-Qi WANG ; Ling-Yu ZENG ; Tao WU ; Lin XIA ; Xi ZHANG
Progress in Biochemistry and Biophysics 2024;51(2):300-308
RNA editing, an essential post-transcriptional reaction occurring in double-stranded RNA (dsRNA), generates informational diversity in the transcriptome and proteome. In mammals, the main type of RNA editing is the conversion of adenosine to inosine (A-to-I), processed by adenosine deaminases acting on the RNAs (ADARs) family, and interpreted as guanosine during nucleotide base-pairing. It has been reported that millions of nucleotide sites in human transcriptome undergo A-to-I editing events, catalyzed by the primarily responsible enzyme, ADAR1. In hematological malignancies including myeloid/lymphocytic leukemia and multiple myeloma, dysregulation of ADAR1 directly impacts the A-to-I editing states occurring in coding regions, non-coding regions, and immature miRNA precursors. Subsequently, aberrant A-to-I editing states result in altered molecular events, such as protein-coding sequence changes, intron retention, alternative splicing, and miRNA biogenesis inhibition. As a vital factor of the generation and stemness maintenance in leukemia stem cells (LSCs), disordered RNA editing drives the chaos of molecular regulatory network and ultimately promotes the cell proliferation, apoptosis inhibition and drug resistance. At present, novel drugs designed to target RNA editing(e.g., rebecsinib) are under development and have achieved outstanding results in animal experiments. Compared with traditional antitumor drugs, epigenetic antitumor drugs are expected to overcome the shackle of drug resistance and recurrence in hematological malignancies, and provide new treatment options for patients. This review summarized the recent advances in the regulation mechanism of ADAR1-mediated RNA editing events in hematologic malignancies, and further discussed the medical potential and clinical application of ADAR1.
8.Advances in animal models of chronic heart failure and its applications in traditional Chinese medicine.
Qian ZHANG ; Xiao-Hong WEI ; Jie CHEN ; Xue-Fen WU ; Xiao-Feng XIA ; Yu-Zhuo WU ; Ling-Yan WANG ; Huan XIA ; Gui-Yang XIA ; Sheng LIN ; Hong-Cai SHANG
China Journal of Chinese Materia Medica 2023;48(3):614-624
Chronic heart failure(CHF) is a series of clinical syndromes in which various heart diseases progress to their end stage. Its morbidity and mortality are increasing year by year, which seriously threatens people's life and health. The diseases causing CHF are complex and varied, such as coronary heart disease, hypertension, diabetes, cardiomyopathy and so on. It is of great significance to establish animal models of CHF according to different etiologies to explore the pathogenesis of CHF and develop drugs to prevent and treat CHF induced by different diseases. Therefore, based on the classification of the etiology of CHF, this paper summarizes the animal models of CHF widely used in recent 10 years, and the application of these animal models in traditional Chinese medicine(TCM) research, in order to provide ideas and strategies for studying the pathogenesis and treatment of CHF, and provide ideas for TCM modernization research.
Animals
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Medicine, Chinese Traditional
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Heart Failure
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Heart Diseases
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Chronic Disease
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Models, Animal
9.Single-dose AAV-based vaccine induces a high level of neutralizing antibodies against SARS-CoV-2 in rhesus macaques.
Dali TONG ; Mei ZHANG ; Yunru YANG ; Han XIA ; Haiyang TONG ; Huajun ZHANG ; Weihong ZENG ; Muziying LIU ; Yan WU ; Huan MA ; Xue HU ; Weiyong LIU ; Yuan CAI ; Yanfeng YAO ; Yichuan YAO ; Kunpeng LIU ; Shifang SHAN ; Yajuan LI ; Ge GAO ; Weiwei GUO ; Yun PENG ; Shaohong CHEN ; Juhong RAO ; Jiaxuan ZHAO ; Juan MIN ; Qingjun ZHU ; Yanmin ZHENG ; Lianxin LIU ; Chao SHAN ; Kai ZHONG ; Zilong QIU ; Tengchuan JIN ; Sandra CHIU ; Zhiming YUAN ; Tian XUE
Protein & Cell 2023;14(1):69-73
10.Predictive analysis of the number of hospitalized patients with acute pancreatitis based on time series model
Xinyi ZENG ; Xiao PAN ; Huan XU ; Han ZHANG ; Huifang XIA ; Xiaomin SHI ; Lei SHI ; Yan PENG ; Xiaowei TANG
Chinese Journal of Pancreatology 2023;23(4):251-256
Objective:To predict and analyze the number of acute pancreatitis (AP) inpatients based on time series model, and to explore the predictive efficiency of the model.Methods:Clinical data of AP inpatients in the Affiliated Hospital of Southwest Medical University from January 2014 to December 2019 were collected. R software was used to collect the time series of AP inpatients, and the trend and seasonal characteristics of AP inpatients from 2014 to 2018 were analyzed. Furthermore, the autoregressive moving average (ARIMA) model was established through stationarity test, model ordering and model testing steps, and the best selected model was used to predict the monthly number of inpatients in 2019 to verify its prediction efficiency.Results:A total of 3 939 AP patients were included in the study. The most common etiology for AP was cholestrogenic (48.2%), followed by hyperacylglyceremia (36.3%). The peak age of hospitalization was from 40 to 60 years old. Time series analysis showed that the number of AP inpatients increased year by year. The highest peak of the disease was from February to March, followed by September to November; and there was seasonal variation and the incidence was relatively small in summer. The established original training set sequence did not pass the stationarity test ( P=0.061), so the ARIMA model was established after it was transformed into a stationarity sequence by first-order difference. According to the criterion of minimum AIC value, ARIMA(2, 1, 1)(1, 1, 1) 12 was selected as the best model. The model was used to predict the number of AP inpatients in 2019, showing that it could better fit the trend of onset time and had good short-term prediction effect. The mean root error and absolute error were 6.8790 and 4.7783, respectively. Conclusions:The number of AP inpatients increases year by year with seasonal changes. ARIMA model is effective in predicting the number of AP inpatients and can be used for short-term prediction.

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