1.Human umbilical cord mesenchymal stem cell-derived exosomes attenuate renal ischemia-reperfusion injury by up-regulating ATF3 to inhibit the TLR4/NF-κB pathway
Xingyu* WAN ; Yujia LIU ; Ruiyan WANG ; Hao WANG ; Yi ZHAO ; Lu GUO ; Zhihua YANG ; Xinghua LÜ
Organ Transplantation 2026;17(2):275-286
Objective To investigate the protective effect and underlying mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) on renal ischemia-reperfusion injury (IRI). Methods hucMSC-Exos were isolated and characterized. A mouse renal IRI model was established and the animals were divided into Sham, IRI, IRI+hucMSC-Exo, IRI+hucMSC-Exo+JY-2 and Sham+JY-2 groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. Hematoxylin-eosin (HE) staining was used to evaluate renal histopathology. Enzyme-linked immune absorbent assay was performed to determine serum interleukin (IL)-1β and IL-18 levels. Western blotting was used to detect the expression of activating transcription factor 3 (ATF3), Toll-like receptor 4 (TLR4), nuclear factor (NF)-κB, NOD-like receptor protein 3 (NLRP3), cysteineyl aspartate specific proteinase (Caspase)-1 p20 and Gasdermin D(GSDMD). Real-time fluorescent quantitative polymerase chain reaction was employed to measure ATF3, TLR4 and NF-κB messenger RNA (mRNA). Immunohistochemistry was conducted to examine NLRP3, Caspase-1 p20 and GSDMD. An in vitro hypoxia/reoxygenation (H/R) model was established in HK-2 cells and divided into Control, H/R, H/R+hucMSC-Exo, H/R+hucMSC-Exo+JY-2 and Control+JY-2 groups. Western blotting was used to detect the expression of ATF3, TLR4 and NF-κB. Real-time fluorescent quantitative polymerase chain reaction was used to measure NLRP3, GSDMD and Caspase-1 mRNA. Results HucMSC-Exos were successfully isolated and identified. Compared with the Sham group, the IRI group exhibited elevated Scr and BUN, higher tubular injury scores, increased protein expression levels of ATF3, TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD, and raised mRNA expression levels of ATF3, TLR4, NF-κB. Compared with the IRI group, the IRI+hucMSC-Exo group showed decreased Scr and BUN, lower tubular injury scores, up-regulated ATF3 protein and mRNA, down-regulated TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD protein, and declined TLR4 and NF-κB mRNA. Compared with the IRI+hucMSC-Exo group, the IRI+hucMSC-Exo+JY-2 group exhibited increased Scr and BUN levels, elevated renal tubular injury scores, decreased ATF3 protein expression levels, elevated protein expression levels of TLR4, NF-κB p65, NLRP3, Caspase-1 p20, and GSDMD, decreased ATF3 mRNA expression levels, and elevated mRNA expression levels of TLR4 and NF-κB. (all P < 0.05). Compared with the Control group, the expression levels of ATF3, TLR4 and NF-κB p65 proteins were increased in the H/R group, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased. Compared with the H/R group, the expression level of ATF3 protein was increased, the expression levels of TLR4 and NF-κB p65 proteins were decreased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were decreased in the H/R+hucMSC-Exo group. Compared with the H/R+hucMSC-Exo group, the expression level of ATF3 protein was decreased, the expression levels of TLR4 and NF-κB p65 proteins were increased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased in the H/R+hucMSC-Exo+JY-2 group (all P < 0.05). Conclusions HucMSC-Exos alleviate renal IRI by up-regulating ATF3, thereby negatively regulating the TLR4/NF-κB signaling pathway and subsequently inhibiting pyroptosis.
2.Technology optimization and in vitro anti-tumor effect evaluation of reactive oxygen species-responsive metho-trexate-modified paclitaxel/icariin micelles
Naijian ZOU ; Liang KONG ; Lei CHANG ; Pengbo WAN ; Xiaolin JIANG ; Mingdian YUAN ; Yingqiang LU
China Pharmacy 2025;36(3):285-292
OBJECTIVE To prepare reactive oxygen species (ROS)-responsive methotrexate (MTX)-modified paclitaxel (PTX)/icariin (ICA) micelles (MTX-oxi-Ms@PTX/ICA), and perform technology optimization and in vitro anti-tumor effect evaluation. METHODS Synergistic toxicity concentration range of PTX and ICA was screened by synergistic toxicity test. The micelles were prepared by thin film hydration method, and their technology was optimized by response surface methodology. The fundamental characteristics of the micelles prepared by the optimal technology were evaluated. The micelles’ cytotoxicity, targeting ability to renal carcinoma RENCA cells of mice, and their inhibitory effects on invasion and migration were assessed. RESULTS Results of synergistic toxicity experiments demonstrated that the strongest synergistic effect occurred when PTX concentrations ranged from 2.5 to 10 μmol/L and ICA concentrations ranged from 5 to 15 μmol/L. The optimal technology of MTX-oxi-Ms@PTX/ ICA was determined to include 80 mg Soluplus®, Soluplus® and TPGS1000 mass ratio of 4∶1 (mg/mg), 2 mg DSPE-PEG2000-TK- PEG5000, 2 mg DSPE-PEG2000-MTX, 1 mg PTX, and 1.5 mg ICA, with a hydration temperature of 35 ℃ and a formulation volume of 5 mL. Under the optimal conditions, average encapsulation efficiency of PTX and ICA in 3 batches of MTX-oxi- Ms@PTX/ICA reached 92.75%, the critical micelle concentration (CMC) was 0.007 9 mg/mL, the particle size was (62.09±1.68) nm, the polydispersity index (PDI) was 0.046±0.032, and the Zeta potential was (-2.47±0.15) mV. Within 30 days of placement, there was no significant change E-mail:yingqiang_1126@163.com in particle size and polydispersity index of micelle. In vitro release experiments showed that MTX-oxi-Ms@PTX/ICA released drugs more rapidly in oxidative environments. The half maximal inhibitory concentration of MTX-oxi-Ms@PTX/ICA against RENCA cells was (5.170±0.036) μmol/L. In vitro cellular uptake experiments indicated that compared with unmodified micelles, MTX modified micelles had stronger targeting effects on cancer cells, and also significantly enhanced the inhibitory ability of invasion and migration of RENCA cells (P<0.05). CONCLUSIONS MTX-oxi-Ms@PTX/ICA micelles are successfully prepared, which exhibit high encapsulation efficiency, low critical micelle concentration, and good stability. These micelles demonstrate significant cytotoxicity against RENCA cells and effectively inhibit cancer cell invasion and migration.
3.Effect of Modified Chaihu Shugansan on CaMKⅡ/CREB Signaling Pathway in Rats with Myocardial Ischemia and Depression
Fen WAN ; Xiaohong LI ; Ying CHEN ; Yangyu PAN ; Yanna LUO ; Fangge LU ; Chuncheng ZHENG ; Pengyun KONG ; Chengxiang WANG ; Liqiang YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):1-11
ObjectiveTo observe the effects of modified Chaihu Shugansan on the calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)/cAMP-response element binding protein (CREB) signaling pathway in the hippocampus and heart tissue of a rat model with myocardial ischemia and depression and explore the mechanism by which this formula prevents and treats coronary heart disease combined with depression. MethodsThe model of myocardial ischemia combined with depression was established by high-fat diet, intraperitoneal injection of isoproterenol (ISO), and chronic unpredictable mild stress (CUMS). A total of 108 SD male rats were randomly divided into normal group, model group, high (23.4 g·kg-1), medium (11.7 g·kg-1), and low (5.85 g·kg-1) dose groups of modified Chaihu Shugansan, CaMKⅡ inhibitor (KN93) group, and KN93 + high, medium, and low dose groups of modified Chaihu Shugansan, with 12 rats in each group. From the first day of modeling to the end of modeling, drugs were administered once a day. In the seventh and eighth weeks, the KN93 group and the KN93 + high, medium, and low dose groups of modified Chaihu Shugansan were intraperitoneally injected with KN93 three times weekly. At the end of the eighth week, behavioral tests including sucrose preference, open field, and elevated plus maze were conducted. Electrocardiogram (ECG) lead Ⅱ changes were observed in each group of rats, and hematoxylin-eosin (HE) staining was performed to observe changes in heart tissue. Serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and lactate dehydrogenase (LDH) were measured by using an enzyme-labeled instrument. Creatine kinase (CK) and creatine kinase-MB (CK-MB) were detected by ultraviolet spectrophotometry, while serum monocyte chemoattractant protein-1 (MCP-1) was measured by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect mRNA expression of CaMKⅡ and CREB in hippocampal and heart tissue, and Western blot was performed to assess protein expression of CaMKⅡ, phosphorylated (p)-CaMKⅡ, CREB, and p-CREB. ResultsCompared to the normal group, the model group showed significant reductions in sucrose preference rate, total activity distance in the open field, number of entries into the center area of the open field, and percentage of entries into the open arms of the elevated plus maze (P<0.01). The ECG showed ST-segment elevation, and HE staining showed serious degeneration of myocardial fibers, disordered arrangement, and infiltration of a large number of inflammatory cells. In addition, serum TC and LDL levels increased (P<0.01), and HDL level decreased (P<0.01). CK, CK-MB, LDH, and MCP-1 levels significantly increased (P<0.05, P<0.01). The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB decreased in the hippocampal tissue (P<0.05, P<0.01), but those increased in the heart tissue (P<0.01). Compared to the model group, the high, medium, and low dose groups of modified Chaihu Shugansan showed improvements in these abnormalities. The KN93 group had reduced sucrose preference, total activity distance in the open field, number of entries into the center area of the open field, and percentage of entries into the open arms of the elevated plus maze (P<0.01), as well as decreased serum CK, CK-MB, LDH, and MCP-1 levels (P<0.05, P<0.01). KN93 also reduced ST-segment elevation, alleviated the degeneration degree of myocardial fibrosis, and lowered inflammatory cell infiltration. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB in both the hippocampal and heart tissue were reduced (P<0.05, P<0.01). The KN93 + high, medium, and low dose groups of modified Chaihu Shugansan showed further improvements in these abnormalities compared to the KN93 group. ConclusionThe modified Chaihu Shugansan exerts antidepressant and myocardial protective effects in rats with myocardial ischemia and depression, possibly related to bidirectional regulation of the CaMKⅡ/CREB signaling pathway, with the high-dose modified Chaihu Shugansan showing the best effects.
4.Impact of human papillomavirus and coinfection with other sexually transmitted pathogens on male infertility.
Xin FAN ; Ya XU ; Li-Feng XIANG ; Lu-Ping LIU ; Jin-Xiu WAN ; Qiu-Ting DUAN ; Zi-Qin DIAN ; Yi SUN ; Ze WU ; Yun-Hua DONG
Asian Journal of Andrology 2025;27(1):84-89
This study primarily aimed to investigate the prevalence of human papillomavirus (HPV) and other common pathogens of sexually transmitted infections (STIs) in spermatozoa of infertile men and their effects on semen parameters. These pathogens included Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae, Pseudomonas aeruginosa , and Staphylococcus aureus . A total of 1951 men of infertile couples were recruited between 23 March 2023, and 17 May 2023, at the Department of Reproductive Medicine of The First People's Hospital of Yunnan Province (Kunming, China). Multiplex polymerase chain reaction and capillary electrophoresis were used for HPV genotyping. Polymerase chain reaction and electrophoresis were also used to detect the presence of other STIs. The overall prevalence of HPV infection was 12.4%. The top five prevalent HPV subtypes were types 56, 52, 43, 16, and 53 among those tested positive for HPV. Other common infections with high prevalence rates were Ureaplasma urealyticum (28.3%), Ureaplasma parvum (20.4%), and Enterococcus faecalis (9.5%). The prevalence rates of HPV coinfection with Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae , and Staphylococcus aureus were 24.8%, 25.4%, 10.6%, 6.4%, 2.4%, 7.9%, 5.9%, 0.9%, and 1.3%, respectively. The semen volume and total sperm count were greatly decreased by HPV infection alone. Coinfection with HPV and Ureaplasma urealyticum significantly reduced sperm motility and viability. Our study shows that coinfection with STIs is highly prevalent in the semen of infertile men and that coinfection with pathogens can seriously affect semen parameters, emphasizing the necessity of semen screening for STIs.
Humans
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Male
;
Infertility, Male/epidemiology*
;
Coinfection/microbiology*
;
Papillomavirus Infections/virology*
;
Adult
;
Sexually Transmitted Diseases/complications*
;
China/epidemiology*
;
Staphylococcus aureus/isolation & purification*
;
Chlamydia trachomatis/isolation & purification*
;
Prevalence
;
Mycoplasma genitalium/isolation & purification*
;
Ureaplasma urealyticum/isolation & purification*
;
Neisseria gonorrhoeae/isolation & purification*
;
Enterococcus faecalis/isolation & purification*
;
Streptococcus agalactiae/isolation & purification*
;
Herpesvirus 2, Human/genetics*
;
Pseudomonas aeruginosa/isolation & purification*
;
Semen/virology*
;
Sperm Motility
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Spermatozoa/microbiology*
;
Human Papillomavirus Viruses
5.Prediction of testicular histology in azoospermia patients through deep learning-enabled two-dimensional grayscale ultrasound.
Jia-Ying HU ; Zhen-Zhe LIN ; Li DING ; Zhi-Xing ZHANG ; Wan-Ling HUANG ; Sha-Sha HUANG ; Bin LI ; Xiao-Yan XIE ; Ming-De LU ; Chun-Hua DENG ; Hao-Tian LIN ; Yong GAO ; Zhu WANG
Asian Journal of Andrology 2025;27(2):254-260
Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans
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Male
;
Azoospermia/diagnostic imaging*
;
Deep Learning
;
Testis/pathology*
;
Retrospective Studies
;
Adult
;
Ultrasonography/methods*
;
Sperm Retrieval
;
Sertoli Cell-Only Syndrome/diagnostic imaging*
6.Molecular targeted therapy for progressive low-grade gliomas in children.
Yan-Ling SUN ; Miao LI ; Jing-Jing LIU ; Wen-Chao GAO ; Yue-Fang WU ; Lu-Lu WAN ; Si-Qi REN ; Shu-Xu DU ; Wan-Shui WU ; Li-Ming SUN
Chinese Journal of Contemporary Pediatrics 2025;27(6):682-689
OBJECTIVES:
To evaluate the efficacy of molecular targeted agents in children with progressive pediatric low-grade gliomas (pLGG).
METHODS:
A retrospective analysis was conducted on pLGG patients treated with oral targeted therapies at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, from July 2021. Treatment responses and safety profiles were assessed.
RESULTS:
Among the 20 enrolled patients, the trametinib group (n=12, including 11 cases with BRAF fusions and 1 case with BRAF V600E mutation) demonstrated 4 partial responses (33%) and 2 minor responses (17%), with a median time to response of 3.0 months. In the vemurafenib group (n=6, all with BRAF V600E mutation), 5 patients achieved partial responses (83%), showing a median time to response of 1.0 month. Comparative analysis revealed no statistically significant difference in progression-free survival rates between the two treatment groups (P>0.05). The median duration of clinical benefit (defined as partial response + minor response + stable disease) was 11.0 months for vemurafenib and 18.0 months for trametinib. Two additional cases, one with ATM mutation treated with olaparib for 24 months and one with NF1 mutation receiving everolimus for 21 months, discontinued treatment due to sustained disease stability. No severe adverse events were observed in any treatment group.
CONCLUSIONS
Molecular targeted therapy demonstrates clinical efficacy with favorable tolerability in pLGG. Vemurafenib achieves high response rates and induces early tumor shrinkage in patients with BRAF V600E mutations, supporting its utility as a first-line therapy.
Humans
;
Glioma/genetics*
;
Male
;
Female
;
Child
;
Child, Preschool
;
Retrospective Studies
;
Brain Neoplasms/genetics*
;
Molecular Targeted Therapy/adverse effects*
;
Adolescent
;
Infant
;
Proto-Oncogene Proteins B-raf/genetics*
;
Pyrimidinones/therapeutic use*
;
Mutation
7.Dynamic changes in serum microRNA-15b and vascular endothelial growth factor in preterm infants with bronchopulmonary dysplasia and their value in assessing neurodevelopment.
Qian CHEN ; Pei-Pei ZHANG ; Qing-Hua LU ; Zhen-Xia WAN ; Lei HUANG
Chinese Journal of Contemporary Pediatrics 2025;27(9):1062-1070
OBJECTIVES:
To investigate the dynamic changes in serum microRNA-15b (miR-15b) and vascular endothelial growth factor (VEGF) in preterm infants with mild or moderate-to-severe bronchopulmonary dysplasia (BPD), as well as their value in assessing short-term neurodevelopment.
METHODS:
A retrospective analysis was conducted on the medical data of 156 preterm infants with BPD who were admitted to the neonatal intensive care unit from January 2020 to February 2023. According to the severity of BPD, they were divided into a mild group (n=88) and a moderate-to-severe group (n=68). Serum levels of miR-15b and VEGF were measured on postnatal days 1, 7, 14, and 28. Repeated measures analysis of variance was used to assess the dynamic changes in serum levels of miR-15b and VEGF. The mediating effect of VEGF between miR-15b and short-term neurological development was tested and analyzed using the stepwise regression method and the Bootstrap method. Logistic regression analysis was used to identify factors influencing adverse neurodevelopmental outcomes.
RESULTS:
In the mild group, there was a significant reduction in the serum level of miR-15b and a significant increase in VEGF over time (P<0.05), while in the moderate-to-severe group, there was a significant increase in miR-15b and a significant reduction in VEGF over time (P<0.05). Serum miR-15b and VEGF levels were important factors influencing neurodevelopmental outcomes, showing independent correlations (P<0.001). The mediating effect analysis indicated that miR-15b indirectly affected short-term neurodevelopment by inhibiting VEGF expression [indirect effect: -0.705 (95%CI: -1.178 to -0.372)], with the indirect effect accounting for 54.36% of the total effect.
CONCLUSIONS
There are different changing trends in serum levels of miR-15b and VEGF in preterm infants with mild and moderate-to-severe BPD. miR-15b primarily influences neurodevelopment through VEGF.
Humans
;
Bronchopulmonary Dysplasia/physiopathology*
;
MicroRNAs/blood*
;
Vascular Endothelial Growth Factor A/blood*
;
Infant, Newborn
;
Infant, Premature/blood*
;
Female
;
Male
;
Retrospective Studies
;
Child Development
;
Nervous System/growth & development*
8.Resection of mediastinal tumor combined with persistent left superior vena cava: A case report
Zongjun XIANG ; Fan ZHANG ; Lei LI ; Yongguo LU ; Xiaoming LI ; Haide MU ; Xiaowei ZHOU ; Linqi YANG ; Zhiyu WAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(07):1044-1046
Persistent left superior vena cava is a rare venous variant that is often combined with cardiovascular malformations. In thoracic surgery, especially mediastinal tumor resection, neglect of this variant may make the surgery difficult and risky, and careful preoperative imaging interpretation and adequate preoperative evaluation play an important role in the perioperative safety of the patient. In this paper, we reported a case of a 17-year-old female patient with a persistent left superior vena cava combined with mediastinal tumors. She was successfully discharged 5 days after thoracoscopic surgery, and after 3 years of postoperative follow-up, no tumor recurrence was observed.
9.Epidemiological characteristics of dengue fever in Shenzhen City in 2024
Jia WAN ; Cong NIU ; Wei LIU ; Liangqiang LIN ; Fan YANG ; Ziquan LÜ ; Zhen ZHANG ; Tiejian FENG ; Jianhua LU ; Dongfeng KONG
Chinese Journal of Schistosomiasis Control 2025;37(5):517-523
Objective To investigate the epidemiological characteristics of dengue fever in Shenzhen City in 2024, so as to provide insights into formulation of the preventive and control measures for dengue fever. Methods The epidemiological data of dengue cases reported in Shenzhen City in 2024 were extracted from the China Disease Prevention and Control Information System and field epidemiological survey data of dengue fever in Shenzhen City, and the temporal, regional and population distributions of dengue fever cases, source of acquire dengue virus infections, disease diagnosis and treatment and outbreaks were analyzed. The dengue virus nucleic acid was tested and the serotypes of dengue virus were characterized using real-time quantitative reverse transcription PCR (RT-qPCR) assay, and the dengue virus gene was sequenced using next-generation sequencing (NGS). In addition, the surveillance on the density of Aedes albopictus was performed using Breteau index (BI) and mosquito oviposition index (MOI). Results A total of 1 735 dengue fever cases were reported in Shenzhen City in 2024, including 952 local cases and 783 imported cases. Most imported dengue fever cases acquired infections from eight cities of Foshan, Guangzhou, Zhongshan, Jiangmen, Dongguan, Zhaoqing, Huizhou, and Zhuhai in the Pearl River Delta region (664 cases, 84.8% of total imported cases) into Baoan, Longgang, and Nanshan districts. The epidemic exhibited an early onset and rapid progression, peaking during the period between September and November (1 632 cases, 94.1% of total cases), and dengue fever cases were distributed across 73 subdistricts in 10 districts, with most cases reported in densely populated central and western regions. The dengue fever cases had a male-to-female ratio of 1.9∶1.0, and a median age of 37 (21) years, with a higher median age among local cases than among imported cases [40 (20) years vs. 33(15) years; Z = -10.30, P < 0.05]. Housework, unemployment, workers, and business service were predominant occupations (1 405 cases, 81.0% of total cases), and there was a significant difference in the constituent ratio of occupations between local and imported cases (χ2 = 92.30, P < 0.05). Among the 1 735 dengue fever cases, the median duration from onset to definitive diagnosis was 3.3 (2.9) days, and 1 686 cases (97.2%) were identified in healthcare facilities, with a low rate of hospitalization and isolation seen in 1 701 inpatients with available epidemiological data (485 cases, 28.5% of total inpatients). A total of 29 outbreaks of dengue fever occurred in Shenzhen City across 2024, which primarily in construction sites (27 outbreaks, 93.1% of total). Dengue virus type I was the dominant serotype causing dengue fever in Shenzhen City in 2024. Sequencing showed that the genomes of dengue virus from multiple dengue fever cases in Shenzhen City shared a high sequence homology with those from cities neighboring Shenzhen City, and there might be intra-city transmission of dengue virus among multiple construction sites in Shenzhen City. The Aedes albopictus density was significantly higher in Shenzhen City in 2024 than in 2023, peaking from May to September. The annual MOI values ranged from 0.9 to 14.0, and the BI values ranged from 0.6 to 6.0. Conclusions The overall epidemic of dengue fever was severe in Shenzhen City in 2024, which was greatly affected by case importation from neighboring cities, construction sites-centered local transmission, and the effectives of routine mosquito vector control was not satisfactory. Integrated dengue fever control measures should be implemented, focusing on regional joint prevention and control mechanisms, capacity building for mosquito vector control, addressing challenges in epidemic containment at construction sites, and strengthening case detection and management systems.
10.Mechanism of the pretreatment with electroacupuncture of "biaoben acupoint combination" for regulating cardiomyocyte mitochondrial fission in the rats of myocardial ischemia-reperfusion injury.
Yanlin ZHANG ; Song WU ; Qianru GUO ; Yuntao YU ; Sunyi WANG ; Yuqi WEI ; Xiaoman WAN ; Zhen LU ; Xiaoru HE
Chinese Acupuncture & Moxibustion 2025;45(3):335-344
OBJECTIVE:
To observe the effect of electroacupuncture (EA) pretreatment of "biaoben acupoint combination" on cardiomyocyte mitochondrial fission in the rats with myocardial ischemia-reperfusion injury (MIRI) and explore its mechanism.
METHODS:
Fifty male SD rats were randomly divided into a sham-operation group, a model group, an EA pretreatment group, an EA pretreatment + Compound C group and an EA pretreatment+ML385 group, 10 rats in each group. In the EA pretreatment, the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, EA was delivered at bilateral "Neiguan" (PC6), "Zusanli" (ST36) and "Guanyuan" (CV4) for 20 min, with continuous wave and 2 Hz of frequency, 1 mA of current, once daily for consecutive 7 days. On day 8, in the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, 30 min before model preparation, the intraperitoneal injection with Compound C (0.3 mg/kg) and ML385 (30 mg/kg) was administered respectively. Except in the sham-operation group, the ligation of the left anterior descending coronary artery was performed to prepare MIRI rat model in the rest groups. In the sham-operation group, the thread was not ligated. After modeling, the content of reactive oxygen species (ROS) in the ischemic area was measured by flow cytometry, superoxide dismutase (SOD) was detected using xanthine oxidase method, and malondialdelyde (MDA) was detected using thiobarbituric acid (TBA) chromatometry. The morphology of myocardial tissue in the ischemic area was observed with HE staining, and the mitochondria ultrastructure of cardiomyocytes observed under transmission electron microscopy. Using immunofluorescence analysis, the positive expression of mitochondrial fission factor (MFF), mitochondrial fission 1 protein antibody (Fis1) and dynamin-related protein 1 (Drp1) was detected; and with immunohistochemical method used, the protein expression of adenosine monophosphate-activated protein kinase (AMPK), nuclear factor E2-associated factor2 (Nrf2) and Drp1 in the ischemic area was detected.
RESULTS:
Compared with the sham-operation group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 increased in the model group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 decreased (P<0.01), and the protein expression of Drp1 elevated (P<0.01). Compared with the model group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 were dropped in the EA pretreatment group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 rose (P<0.01), and the protein expression of Drp1 declined (P<0.01); and in the EA pretreatment+Compound C group and the EA pretreatment+ML385 group, the positive expression of MFF, Fis1 and Drp1, and the protein expression of Drp1 were all reduced (P<0.01). When compared with the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 were dropped in the EA pretreatment group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 rose (P<0.01, P<0.05), and the protein expression of Drp1 decreased (P<0.05). In comparison with the model group, the EA pretreatment+Compound C group and the EA pretreatment+ML385 group, the cardiac muscle fiber rupture, cell swelling and mitochondrial disorders were obviously alleviated in the EA pretreatment group. The morphological changes were similar among the model group, the EA pretreatment+Compound C group and the EA pretreatment+ML385 group.
CONCLUSION
Electroacupuncture pretreatment of "biaoben acupoint combination" attenuates myocardial injury in MIRI rats, probably through promoting the phosphorylation of AMPK and Nrf2, inhibiting the excessive mitochondrial fission induced by Drp1, and reducing mitochondrial dysfunction caused by mitochondrial fragmentation and vacuolation.
Animals
;
Electroacupuncture
;
Male
;
Rats, Sprague-Dawley
;
Myocardial Reperfusion Injury/physiopathology*
;
Myocytes, Cardiac/cytology*
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Rats
;
Acupuncture Points
;
Mitochondrial Dynamics
;
Humans
;
Reactive Oxygen Species/metabolism*
;
NF-E2-Related Factor 2/genetics*
;
Superoxide Dismutase/metabolism*

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