1.Notoginsenoside R1 modulates mitophagy in human cardiomyocytes viathe Pink1/Parkin pathway after hypoxia/reoxygenation
Xiaoman XIONG ; Huan WU ; Shanglin LU ; Yong WANG ; Yuhua ZHENG ; Yi XIANG ; Haiyan ZHOU ; Xingde LIU
Acta Universitatis Medicinalis Anhui 2026;61(1):53-59
ObjectiveTo investigate the mechanism by which Notoginsenoside R1 (NGR1) ameliorates hypoxia/reoxygenation (H/R)-induced injury in AC16 human cardiomyocyte cell lines through the regulation of mitophagy. MethodsCommon genes linked to hypoxia/reoxygenation injury and mitophagy were identified by intersecting data from GeneCards and MitoCarta databases. AC16 cell viability was assessed via CCK-8 assay under varying NGR1 concentrations (0, 6.25, 12.5, 25, 50, 100, 200, 300, 400, 500 μmol/L). AC16 cells were divided into the following groups: control group (Control), model group (H/R), and treatment groups (H/R + NGR1 at 100, 200 and 300 μmol/L). Mitochondrial membrane potential (ΔΨm) was measured using 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining. Transcriptional levels of mitophagy-related genes (Parkin, Pink1, P62) were quantified by reverse transcription-quantitative PCR (RT-qPCR). Protein expression of mitophagy-related markers (Parkin, Pink1, P62, and LC3BⅡ) was evaluated via Western blot analysis. Mitochondrial ultrastructure was visualized by transmission electron microscopy (TEM). ResultsCompared to the control group, cell viability in the H/R group significantly decreased (P<0.01). Treatment with NGR1 at concentrations above 100 μmol/L significantly enhanced the cell viability of AC16 cells compared to the H/R group (P<0.01). H/R induced a significant decrease in mitochondrial membrane potential (P<0.01), which was restored by NGR1 treatment (P<0.01). The mRNA levels of Parkin, Pink1, and P62 in the H/R group were upregulated compared to the control group (P<0.05), while NGR1 intervention downregulated their expression (P<0.05). Protein expression levels of Parkin, Pink1, and LC3BⅡ in the H/R group significantly increased, while P62 expression decreased compared to the control group (P<0.01). In contrast, different doses of NGR1 treatment significantly reduced the expression of Parkin, Pink1, and LC3BⅡ while increasing P62 expression (P<0.05). TEM revealed that the mitochondrial structure in the H/R group was severely disrupted, with fragmented and disorganized cristae, which was alleviated by NGR1. ConclusionNGR1 ameliorates H/R-induced AC16 cell injury, and its mechanism may be associated with modulating the Pink1/Parkin pathway to suppress excessive mitophagy.
2.Targeting AMPK related signaling pathways:A feasible approach for natural herbal medicines to intervene non-alcoholic fatty liver disease
Yongqing CAIA ; Lu FANG ; Fei CHEN ; Peiling ZHONG ; Xiangru ZHENG ; Haiyan XING ; Rongrong FAN ; Lie YUAN ; Wei PENG ; Xiaoli LI
Journal of Pharmaceutical Analysis 2025;15(1):30-63
Non-alcoholic fatty liver disease(NAFLD)is a metabolic disease characterized by abnormal deposition of lipid in hepatocytes.If not intervened in time,NAFLD may develop into liver fibrosis or liver cancer,and ultimately threatening life.NAFLD has complicated etiology and pathogenesis,and there are no effective therapeutic means and specific drugs.Currently,insulin sensitizers,lipid-lowering agents and hep-atoprotective agents are often used for clinical intervention,but these drugs have obvious side effects,and their effectiveness and safety need to be further confirmed.Adenosine monophosphate(AMP)-activated protein kinase(AMPK)plays a central role in maintaining energy homeostasis.Activated AMPK can enhance lipid degradation,alleviate insulin resistance(IR),suppress oxidative stress and inflammatory response,and regulate autophagy,thereby alleviating NAFLD.Natural herbal medicines have received extensive attention recently because of their regulatory effects on AMPK and low side effects.In this article,we reviewed the biologically active natural herbal medicines(such as natural herbal medicine formulas,extracts,polysaccharides,and monomers)that reported in recent years to treat NAFLD via regulating AMPK,which can serve as a foundation for subsequent development of candidate drugs for NAFLD.
3.Trends of Incidence and Age at Onset of Leukemia in Jiangsu Cancer Registration Areas from 2009 to 2019
Haiyan LU ; Xinxin DONG ; Xingxing ZHU ; Dekun ZHANG ; Yuxue YANG ; Xiaolan ZHAO ; Renqiang HAN ; Jinyi ZHOU ; Ran TAO ; Weigang MIAO ; Pengfei LUO
China Cancer 2025;34(2):125-131
[Purpose]To analyze the trends of incidence and age at onset of leukemia in Jiangsu cancer registration areas from 2009 to 2019.[Methods]The continuous monitoring data of leukemia from 2009 to 2019 were collected from 16 cancer registries in Jiangsu Province.All datasets were checked and evaluated based on data quality control criteria and were included in the analysis.Crude incidence rate(CIR),age-standardized incidence rate by Chinese standard population(ASIRC),the average annual percentage change(AAPC),the standardized average age at onset,the changes in the age structure of incidence and the changes in the birth cohort by year were calculated.[Results]The incidence rate of leukemia significantly increased from 5.22/105 in 2009 to 7.88/105 in 2019,with a significant upward trend(for CIR,AAPC=4.95%,95%CI:3.82%~6.09%;for ASIRC,AAPC=2.97%,95%CI:1.52%~4.43%).The incidence rates were in-creased in all age groups and increased with the birth cohort by years.There was a tendency of backward shift for the age composition of the population,with the increasing of composition for those over 60 years old.The mean age at onset increased from 48.62 years old in 2009 to 57.96 years old in 2019,with a backward shift in the mean age(β=0.773,P<0.001),and the mean age at onset increased with the year only in rural areas after standardization(β=0.428,P=0.017).[Conclusion]Leukemia incidence rate in Jiangsu Province increased from 2009 to 2019,and the age at onset has shifted backwards.It's important to strengthen the early prevention and control of leukemia.
4.Quercetin inhibits zearalenone-induced ferroptosis of porcine small intestinal epi-thelial cells via regulating Nrf2/GPX4 signaling pathway
Haiyan CHEN ; Huifang LU ; Zhigao CAO ; Panfeng SUN ; Shouxuan LIU ; Chao SONG
Chinese Journal of Veterinary Science 2025;45(3):527-534,593
The aim of this study was to investigate the mechanism of quercetin in inhibiting the fer-roptosis induced by zearalenone(ZEN)via mediating the nuclear factor erythroid-2-related factor 2(Nrf2)/glutathione peroxidase 4(GPX4)signaling pathway.IPEC-J2 cells were cultured in vitro and treated with ZEN(25 mg/L)and different concentrations of quercetin(10,20,40 μmol/L).Bi-ochemical methods were used to detect the levels of lactate dehydrogenase(LDH)in the cell cul-ture medium supernatant,total antioxidant capacity(T-AOC),superoxide dismutase(SOD),glu-tathione(GSH),and malondialdehyde(MDA).Fluorescence probes were used to detect the levels of Fe2+,reactive oxygen species(ROS),and lipid peroxidation.Western blot was performed to de-tect the expression levels of Nrf2,long chain acyl CoA synthetase 4(ACSL4),and GPX4.The IPEC-J2 cells were divided into the control group,ZEN group,quercetin group,and ML385(Nrf2 inhibitor)+quercetin group for further analysis.Except for the control group,the other groups were treated with ZEN in the prescence of quercetin and ML385.The changes of Nrf2/GPX4 path-way-related proteins and ferroptosis-related indexes(LDH,Fe2+,MDA,and GSH)were detected.Compared with the control group,IPEC-J2 cells in the ZEN group exhibited a decrease in cell via-bility,T-AOC,and GSH,SOD levels,Nrf2,and GPX4 protein expressions(P<0.05),while LDH release rate,Fe2+and ROS,lipid peroxidation,MDA levels,and ACSL4 protein expression de-creased in the ZEN group(P<0.05).Compared with ZEN group,the cell viability,the levels of T-AOC,SOD and GSH,the protein expression of Nrf2 and GPX4 in quercetin groups were increased(P<0.05),while the LDH release rate,the levels of Fe2+,ROS,lipid peroxidation,and MDA as well as the protein expression of ACSL4 were decreased(P<0.05).Compared with the quercetin group,the protein expression of Nrf2 and GPX4 and the level of GSH in ML385+quercetin group reduced(P<0.05),the LDH release rate and the levels of Fe2+and MDA increased(P<0.05).In summary,quercetin could inhibit ZEN-induced ferroptosis of IPEC-J2 cells,and its mechanism may be related to the induction of Nrf2/GPX4 signaling pathway.
5.Progress on recombinant viral vector vaccines of African swine fever
Yunyun MA ; Wei LIU ; Haiyan LU ; Shandian GAO ; Junjun SHAO ; Huiyun CHANG
Chinese Journal of Veterinary Science 2025;45(4):859-866
African swine fever(ASF)caused by African swine fever virus(ASFV)is a febrile,hem-orrhage and highly fatal infectious disease in pigs,which poses a serious threat to the global pig in-dustry.Currently,no vaccine is available for the prevention and control of ASF,and several ASF vaccines,including gene deletion attenuated live vaccines,live vector vaccines,and subunit vaccines are under the development stage in the laboratory research.As one of the most promising vaccines,live vector vaccine has the characteristic of safety and simulation of the pathogen natural infection to effectively stimulate the innate and adaptive immune responses,which becomes one of the hotspots in the research and development of novel ASF vaccines.This review focuses on the pro-gress in using modified viruses as vectors for ASF live vector vaccines,and aims to provide valua-ble information for future development of safe and effective ASF vector vaccines.
6.Trends analysis of pancreatic cancer mortality in Xuhui district, Shanghai from 1992 to 2021
Jingshu XU ; Jianhua SHI ; Haiyan GU ; Lei CHEN ; Xiaolin QIAN ; Lu LU ; Deng NIU
Journal of Surgery Concepts & Practice 2025;30(1):34-40
Objective To study the death status of pancreatic cancer among residents in Xuhui district, Shanghai, from 1992 to 2021, and analyze its trends of change, so as to provide evidence for the prevention and treatment of pancreatic cancer. Methods Based on the database of Shanghai death registration system from 1992 to 2021, the crude mortality rate, standardized mortality rate, age-specific mortality rate and other indicators of pancreatic cancer among registered residents in Xuhui district were calculated. The Joinpoint software was used to analyze the trends of average annual percent change (AAPC) of pancreatic cancer mortality rate, and the age-period-cohort model was used to analyze the age effect, period effect and birth cohort effect pairs significant changes in pancreatic cancer mortality. Results In 2021, the mortality rate of pancreatic cancer in Xuhui district, Shanghai, ranked fourth among malignant tumors, and the winning rate and world standard rate of the whole population, males and females were 8.34/100 000 (8.81/100 000, 7.98/100 000) and 7.28/100 000 (7.69/100 000, 6.96/100 000), respectively, with males higher than females. AAPC of crude mortality rate and the standardized (6) mortality rate were higher in males than that in females. The age-specific mortality rate increased with the increase of age, and the highest mortality rate was found in 60-84 years old group. The age-period-cohort model showed that from 1992 to 2021, the annual net shift of pancreatic cancer mortality among the whole population, male and female residents in Xuhui district, Shanghai, was 1.22%, 1.58%, 1.15% (P=0.20, 0.19, 0.45) respectively, and the time trend was not significant. From the perspective of age effect, the risk of death from pancreatic cancer in the whole population and with age deviation in males had an obvious trend with increasing age (P<0.05), while the age effect in females had no obvious trend. From the perspective of period effect, no period deviation was significant in the whole population, males and females (P>0.05). In terms of cohort effects, there were significant differences in the whole population and the male cohort deviations(P<0.05). No significant cohort effect was observed in the female population. Conclusions The mortality rate of pancreatic cancer among registered residents in Xuhui district, Shanghai from 1992 to 2021, was on the rise, especially in the 60-84 years old group and male. The prevention and control of pancreatic cancer needs to develop effective epidemic prevention measures for corresponding populations.
7.Clinical characteristics and prognosis analysis of T-lymphoblastic lymphoma
Xiyu LI ; Min ZHANG ; Jingjing ZHANG ; Chunyan YANG ; Qian HUANG ; Haiyan WANG ; Lu JIA ; Lulu CHEN ; Hao ZHANG
Journal of Leukemia & Lymphoma 2025;34(1):30-33
Objective:To investigate the clinical characteristics and prognosis of T-lymphoblastic lymphoma (T-LBL).Methods:A retrospective case series study was conducted. Clinical data of patients diagnosed with T-LBL at the Affiliated Hospital of Jining Medical University from January 2013 to March 2023 were retrospectively analyzed, and their clinical characteristics and prognosis were statistically analyzed.Results:A total of 22 T-LBL patients were included. Among them, there were 19 males (86.4%) and 3 females (13.6%), and the median age at onset was 19.5 (15, 28) years old. Based on Ann Arbor staging, 3 cases (13.6%) were classified as stage Ⅰ-Ⅱ, while 19 cases (86.4%) were stage Ⅲ-Ⅳ; 10 cases (45.5%) presented with B symptoms, 12 cases (54.5%) without B symptoms; 16 cases (72.7%) showed elevated lactic dehydrogenase (LDH) level. At onset, 7 patients (31.8%) had mediastinal masses, 3 patients (13.6%) had central nervous system involvement, and 17 patients (77.3%) had bone marrow involvement. The overall response rate (ORR) and complete remission rate among the 22 patients were 81.82% (18/22) and 31.82% (7/22), respectively. The ORR was 84.21% (16/19) in 19 patients treated with ALL-like regimens. Among 3 patients treated with NHL-like regimens, 1 case achieved complete remission and 1 case achieved partial remission. Seven patients received allogeneic hematopoietic stem cell transplantation, with a median overall survival (OS) time of 22 months; the median OS time of patients without allogeneic hematopoietic stem cell transplantation was 14 months. The 3-year OS rates in the allogeneic hematopoietic stem cell transplantation group and group without allogeneic hematopoietic stem cell transplantation were 64.30% and 16.00%, and the difference in OS between the two groups was statistically significant ( P = 0.043). Two patients with disease progression prior to transplantation died of multidrug-resistant bacterial infections after transplantation. Conclusions:T-LBL is rare, and it is a highly aggressive tumor that predominantly occurs in adolescent males. Allogeneic hematopoietic stem cell transplantation can prolong OS, reduce relapse and improve the prognosis of patients.
8.Toxic effects of chlorinated organophosphate flame retardants on mice via different exposure routes
Jialei ZHU ; Meiyu ZHOU ; Huanhuan ZHU ; Ruiyang TIAN ; Dahua REN ; Haiping LIU ; Xuanying JIANG ; Linfan XU ; Ying LU ; Haiyan CHU
Chinese Journal of Preventive Medicine 2025;59(7):1031-1039
Objective:To evaluate the effects of chlorinated organophosphate flame retardants (Cl-OPFRs) via respiratory and digestive tract exposure on multiple organs in mice.Methods:A short-term repeated exposure model of tris(2-chloroethyl) phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCIPP) and tris(1, 3-dichloro-2-propyl) phosphate (TDCIPP) in mice was established through intratracheal instillation and oral gavage administration. The exposure doses were 0.7, 1 and 2 mg·kg -1·day -1, respectively, with continuous administration for 14 days. The organs of the heart, liver, spleen, lung, kidney, stomach, large intestine, small intestine, bladder and testis were collected and weighed to calculate the organ coefficients. The pathological and histological changes were observed by hematoxylin-eosin staining to quantitatively assess the effects of the three Cl-OPFRs on the various organs by using the pathology score. Results:Analysis of organ coefficients in tracheal drip-treated mice showed that the organ coefficients in the testes of the TCEP, TCIPP and TDCIPP groups were lower than those in the control group ( PTCEP-testis=0.045, PTCIPP-testis=0.012 and PTDCIPP-testis<0.001). The organ coefficients were lower in the lungs and small intestines of the TCEP group ( PTCEP-lung=0.006, PTCEP-small intestine=0.042). The organ coefficients for the stomach and large intestine were higher in the TDCIPP group ( PTDCIPP-stomach=0.014, PTDCIPP-large intestine=0.049). Analyses of gavage-contaminated mice showed that the organ coefficients for liver, stomach and small intestine in the TCEP and TDCIPP groups were higher than those in the control group ( PTCEP-liver=0.007, PTCEP-stomach=0.003, PTCEP-small intestine<0.001, PTDCIPP-liver=0.001, PTDCIPP-stomach=0.004, and PTDCIPP-small intestine<0.001). Histopathological analyses of the organs of tracheal drip dyed mice showed significant pathological damage in the lung tissue of the TCIPP group, mainly in the form of thickening of the interstitium, infiltration of inflammatory cells and alveolar collapse. The results of the analysis of gavage poisoned mice showed that TCIPP exposure could lead to blurring of the red and white medullary boundaries of spleen tissues, destruction of white medullary structures, etc., and induce small intestinal cryptitis. TDCIPP induced significant pathological damage to the liver tissues of mice, which mainly included cytoplasmic washout, infiltration of inflammatory cells, acute inflammation, and other injurious effects. Significant pathological damage to the intestinal tissues of mice was also observed. Conclusions:This study demonstrates that the toxic effects of Cl-OPFRs are significantly associated with exposure routes and compound specificity. Respiratory exposure predominantly induces TCIPP-mediated pulmonary injury, while digestive exposure causes TDCIPP-driven hepatointestinal toxicity. These findings provide preliminary evidence for the toxicity screening of Cl-OPFRs.
9.Epidemiological characteristics of respiratory human adenovirus infections in hospitalized children in Ningbo from 2019 to 2024
Bibo MAO ; Wenbo LU ; Zhuoling LI ; Chengbo ZHOU ; Changshui CHEN ; Haiyan QIU ; Wenyuan LIU
Chinese Journal of Nosocomiology 2025;35(19):2960-2964
OBJECTIVE To investigate the epidemiological characteristics of respiratory human adenovirus(H AdV)infections in hospitalized children in Ningbo,and to provide data for formulating infection prevention and control strategies for HAdV.METHODS A total of 65 022 children hospitalized with respiratory infections at the Women and Children's Hospital of Ningbo University from Jul.2019 to Dec.2024 were selected as the study sub-jects.Multiple reverse transcription-polymerase chain reaction(RT-PCR)and capillary electrophoresis were used to detect 11 non-bacterial pathogens.Basic and clinical information of the children was collected for analysis.RESULTS A total of 65 022 specimens were tested,with 4 292 cases tested positive for HAdV positivity,yielding a positive rate of 6.60%.The lowest positive rate was observed in 2023(3.22%),while the highest was in 2024(13.97%).Compared to the years 2019-2023,the overall HAdV positive rate was high in 2024,peaking at 26.80%in Jun.,indicating an outbreak.The total HAdV positive rate was higher in boys(6.82%)than in girls(6.32%)(P=0.006).The highest HAdV positive rate was observed in the 2 to<6 age group(9.00%),while the lowest was in the 0 to<1 age group(2.33%).Among the HAdV-positive specimens,2 658 cases(61.93%)were single infections,and 1 634 cases(38.07%)were co-infections.The non-bacterial respiratory pathogens with the highest co-infection rates were human rhinovirus(34.09%),Mycoplasma pneumoniae(20.44%)and human parainfluenza virus(5.75%).CONCLUSIONS A n outbreak of HAdV infections is observed among hospitalized children in Ningbo in 2024.Higher positive rates are found in boys aged 2 to<6 years,with a certain proportion of co-infections.
10.Fundus imaging features of glucocorticoid-related central serous chorioretinopathy
Bo JIN ; Pei LIU ; Shu LI ; Chenyu LU ; Guangqi AN ; Haiyan ZHU ; Liping DU ; Xuemin JIN
Chinese Journal of Ocular Fundus Diseases 2025;41(5):358-363
Objective:To compare and observe the fundus imaging characteristics of eyes with glucocorticoid-related central serous chorioretinopathy (CSC).Methods:A retrospective clinical study. A total of 149 CSC patients with 166 eyes diagnosed at Department of Ophthalmology of The First Affiliated Hospital of Zhengzhou University from March 2021 to October 2024 were included in the study. The duration of the disease from the appearance of symptoms to treatment was less than 3 months. All affected eyes underwent best-corrected visual acuity (BCVA), fundus color photography, swept-source optical coherence tomography (SS-OCT), and fundus fluorescein angiography (FFA) examinations. BCVA was tested using an international standard vision chart and converted into logarithm of the minimum angle of resolution (logMAR) visual acuity for statistical analysis. The SS-OCT instrument measured subfoveal choroidal thickness (SFCT), central macular thickness (CMT), choroidal vascular volume (CVV), and the width and height of flat irregular pigment epithelial detachment (FIPED). FIPED, subretinal fibrin, and choroidal layer strong reflective spots were identified from SS-OCTA B-scan images; multiple leakages (leak points >3) were identified from FFA images. Based on the presence or absence of a clear history of glucocorticoid administration before the onset, patients were divided into glucocorticoid-related and non-glucocorticoid-related groups, comprising 41 patients with 53 eyes and 108 patients with 113 eyes, respectively. Clinical and fundus imaging characteristics of the two groups were compared. The comparison of quantitative data between the two groups was performed using independent samples t test or non-parametric independent samples Wilcoxon test; the comparison of qualitative data was performed using χ2 test. Results:Compared with the non-glucocorticoid-related group, the glucocorticoid-related group had a smaller male-to-female ratio and a higher bilateral incidence, and the differences were statistically significant ( χ2=4.925, 17.849; P<0.05). The logMAR BCVA for the glucocorticoid-related and non-glucocorticoid-related groups were 0.45±0.33 and 0.21±0.21, respectively; SFCT were (644.43±131.91) and (507.26±121.79) μm; CMT were (389.51±233.45) and (362.59±140.85) μm; CVV were (4.44±1.07) and (3.67±0.82) mm 3; FIPED incidence were 58.49% (31/58) and 20.35% (23/113), respectively; FIPED width and height were (1 122.01±533.98) and (742.90±388.79) μm, and (99.13±92.17) and (33.01±15.99) μm; subretinal fibrin were observed in 24 (45.28%, 24/53) and 15 (13.27%, 15/113) eyes; choroidal strong reflections were found in 38 (71.70%, 38/53) and 45 (39.82%, 45/113) eyes; multiple leak points were identified in 35 (66.03%, 35/53) and 40 (35.40%, 40/113) eyes, respectively. Compared with the non-glucocorticoid-related group, the glucocorticoid-related group had worse BCVA ( Z=-4.984), thicker SFCT ( t=6.586), larger CVV ( t=5.160), higher incidence of FIPED ( χ2=23.908), and greater width and height of FIPED ( t=2.895, Z=-3.703). The glucocorticoid-related group also had a significantly increased incidence of subretinal fibrin, choroidal strong reflections, and multiple leak points, with all differences being statistically significant ( χ2=20.565, 14.663, 13.675; P<0.05); however, the comparison of CMT showed no statistically significant difference ( Z=-0.651, P>0.05). Conclusion:Compared with non-glucocorticoid-related CSC, glucocorticoid-related CSC patients have poorer vision, are more likely to affect both eyes, show no gender bias; choroidal vascular dilation is more significant, and damage to the outer retina and retinal pigment epithelium is more severe.

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