1.Linagliptin synergizes with cPLA2 inhibition to enhance temozolomide efficacy by interrupting DPP4-mediated EGFR stabilization in glioma.
Dongyuan SU ; Biao HONG ; Shixue YANG ; Jixing ZHAO ; Xiaoteng CUI ; Qi ZHAN ; Kaikai YI ; Yanping HUANG ; Jiasheng JU ; Eryan YANG ; Qixue WANG ; Junhu ZHOU ; Yunfei WANG ; Xing LIU ; Chunsheng KANG
Acta Pharmaceutica Sinica B 2025;15(7):3632-3645
The polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.
2.Evolution and genetic variation of HA and NA genes of H1N1 influenza virus in Shanghai, 2024
Lufang JIANG ; Wei CHU ; Xuefei QIAO ; Pan SUN ; Senmiao DENG ; Yuxi WANG ; Xue ZHAO ; Jiasheng XIONG ; Xihong LYU ; Linjuan DONG ; Yaxu ZHENG ; Yinzi CHEN ; Chenyan JIANG ; Chenglong XIONG ; Jian CHEN
Shanghai Journal of Preventive Medicine 2025;37(9):719-724
ObjectiveTo analyze the evolutionary characteristics and genetic variations of the HA (hemagglutinin) and NA (neuraminidase) genes of influenza A(H1N1) viruses in Shanghai during 2024, to investigate their transmission patterns, and to evaluate their potential impact on vaccine effectiveness. MethodsFrom January to October 2024, throat swab specimens were collected from influenza like illness (ILI) patients at 4 hospitals in Shanghai. Real-time fluorescence ploymerase chain reaction (RT-PCR) was used for virus detection and isolation of H1N1 influenza viruses. Forty influenza A(H1N1) virus strains were sequenced using Illumina NovaSeq 6000 platform, followed by phylogenetic analyses, genetic distance analysis, and amino acid variation analyses of HA and NA genes. ResultsPhylogenetic tree of the HA and NA genes revealed that the 40 influenza A(H1N1) virus strains circulating in Shanghai in 2024 exhibited no significant geographic clustering, with a broad origin of strains and complex transmission chains. Genetic distance analyses demonstrated that the average intra-group genetic distances of HA and NA genes among the Shanghai strains were 0.005 1±0.000 6 and 0.004 6±0.000 6, respectively, which were comparable to or higher than those observed in global surveillance strains. Both HA and NA genes displayed frequent mutations. Compared to the 2023‒2024 and 2024‒2025 Northern Hemisphere A(H1N1) vaccine strains (WHO-recommended), the HA proteins of 40 Shanghai strains exhibited amino acid substitutions at positions 120, 137, 142, 169, 216, 223, 260, 277, 356 and 451, with critical mutations at positions 137 and 142 located within the Ca2 antigenic determinant. Furthermore, mutations in the NA protein were observed at positions 13, 50, 200, 257, 264, 339 and 382. ConclusionThe genetic background of the 2024 Shanghai influenza A(H1N1) virus strains is complex and diverse, and antigenic variation may affect vaccine effectiveness. Therefore, it is recommended to enhance genomic surveillance of influenza viruses, evaluate vaccine suitability, and implement more targeted prevention and control strategies against imported influenza viruses.
3.Tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device in anterior mediastinal masses
Junmin ZHU ; Junjie WANG ; Jianming YUE ; Yixin SUN ; Yichen LIU ; Lei WANG ; Lin LIN ; Jie LI ; Jinlan ZHAO ; Xuehua TU ; Ningying DING ; Jianrong HU ; Chunmei HE ; Leilei TIAN ; Hongtao TANG ; Jiasheng ZHAO ; Cheng CHEN ; Yongxiang SONG ; Yunwei TIAN ; Yong XIAO ; Kaidi LI ; Lin MA ; Yun WANG ; Longqi CHEN ; Dong TIAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(11):1603-1609
Objective To assess the clinical value of a novel surgical technique—Tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device in the resection of anterior mediastinal masses. Methods Patients who underwent tubeless subxiphoid uniportal video-assisted thoracoscopic surgery via balance-shaped sternal elevation device in anterior mediastinal masses process at the Department of Thoracic Surgery, West China Hospital, Sichuan University from March to April 2025 were included, and their clinical data were analyzed. Results A total of 4 patients were included, with 2 males and 2 females, aged 58-75 years. The diameter of the tumor was 2.5-3.0 cm. The operation time was 60.0-150.0 min, intraoperative blood loss was 5-10 mL, pain score on the 3rd day after surgery was 0 points, and postoperative hospital stay was 2-3 days. All patients achieved complete resection of the masses and thymus without perioperative complications. Conclusion The tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device technique optimizes surgical visualization and instrument maneuverability while avoiding complications related to conventional anesthesia and tubing, thereby markedly enhancing the minimally invasive profile of anterior mediastinal masses resections. In addition to maintaining procedural safety, this approach effectively reduces postoperative pain and accelerates patient recovery, highlighting its potential for widespread clinical adoption.
4.Investigation of attention deficit hyperactivity disorder and subthreshold states among children in Chongqing
Xiuying YANG ; Zhanming SHI ; Yi LI ; Jiasheng LIU ; Dengguo CHENG ; Tingting HE ; Wei ZHAO ; Gang YUAN ; Ludan ZHANG ; Chunni HUANG ; Junhao LUAN ; Xiaoyue JIA ; Tiantian CHEN ; Mei WANG ; Shiping ZHENG ; Chunying WU ; Yuanming REN ; Mengfei LI
Sichuan Mental Health 2025;38(6):561-567
BackgroundAttention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by age-inappropriate inattention, excessive activities incongruous with setting, and emotional impulsivity. Subthreshold ADHD (sADHD) is clinically defined as the presence of ADHD symptoms that do not meet the full diagnostic criteria for ADHD. Children with sADHD exhibit deficits in executive function, demonstrate more conduct, learning, and anxiety-related problems compared to typically developing children, and show even poorer working memory performance than children diagnosed with ADHD. Currently, there is limited epidemiological research on sADHD in China, with few studies simultaneously investigating the prevalence of both ADHD and sADHD in children. ObjectiveTo investigate the prevalence of ADHD and sADHD among children aged 6–13 years in Chongqing, analyzing their distribution characteristics within this population, with the aim of providing references for developing preventive measures against both ADHD and sADHD. MethodsFrom October to November 2023, a total of 3 398 students in grades 1–6 from six primary schools in Jiangbei District, Chongqing were selected using a stratified cluster random sampling method. The occurrence of ADHD and sADHD was evaluated by using the short version (18-item version) of the Swanson, Nolan, and Pelham IV rating scales (SNAP-IV) and the Chinese vision of Schedule for Affective Disorder and Schizophrenia for School-aged Children-Present and Lifetime Version (K-SADS-PL). ResultsThe ADHD detection rate among children in Chongqing was 1.90% (95% CI: 0.014–0.024). Boys showed a significantly higher ADHD detection rate than girls (χ2=7.733, P=0.005). No statistically significant differences were found in ADHD detection rates across different grades or age groups (χ2=7.347, 12.362, P>0.05). The sADHD detection rate was 6.32% (95% CI: 0.054–0.072). Similarly, boys exhibited significantly higher sADHD detection rates than girls (χ2=21.005, P<0.01). Significant differences emerged across different grades (χ2=20.559, P=0.001), while no statistically significant difference was observed in age groups (χ2=12.070, P=0.060). ConclusionThe ADHD detection rates were comparable across all grade levels and age groups from 6–13 years old. Second-grade children demonstrated notably higher sADHD rates compared to other grades, while boys demonstrated higher prevalence rates than girls for both ADHD and sADHD. [Funded by Science and Health Joint Medical Research Project in Jiangbei District, Chongqing City in the Second Half of 2023 (number, 2023JBKWLH022)]
5.Expression of OTUD3,ILF2 in esophageal squamous cell cancer tissue and their relationship with clinical pathological characteristics and prognosis
Huijuan YU ; Yong XIN ; Hongying YIN ; Jiasheng ZHAO ; Li LI
International Journal of Laboratory Medicine 2024;45(17):2098-2102
Objective To investigate the expression of OTU deubiquitinase 3(OTUD3)and interleukin en-hancer binding factor 2(ILF2)in esophageal squamous cell cancer and their correlation with clinicopathologi-cal characteristics and prognosis.Methods A total of 102 patients with esophageal squamous cell cancer who underwent radical resection in Huai'an Fifth People's Hospital between January 2019 and July 2020 were in-cluded in this study.Immunohistochemistry was used to detect OTUD3 and ILF2 expression.Spearman rank correlation analysis was conducted to assess the relationship between OTUD3 and ILF2.Kaplan-Meier surviv-al curves were used to analyze the impact of OTUD3 and ILF2 expression on patient survival prognosis.COX regression analysis was employed to identify prognostic factors.Results Compared with adjacent tissues,the positive rate of OTUD3 was lower and the positive rate of ILF2 was higher in esophageal squamous cell cancer tissues,and the differences were statistically significant(P<0.05).A significant negative correlation was ob-served between the expression of OTUD3 and ILF2 in esophageal squamous cell cancer(r=-0.712,P<0.001).Furthermore,patients with TNM stage Ⅲ,low differentiation,and lymph node metastasis exhibited a lower positive rate of OTUD3 and a higher positive rate of ILF2 compared to patients with TNM stage Ⅰ-Ⅱ,medium-high differentiation,and no lymph node metastasis(P<0.05).The 3-year survival rate for the OTUD3-positive group was significantly higher than that of the OTUD3-negative group(Log-rank x2=5.869,P=0.015).The 3-year survival rate for the ILF2-positive group was significantly lower than that of the ILF2-negative group(Log-rank x2=16.257,P<0.001).TNM staging,lymph node metastasis,degree of differentiation,OTUD3,and ILF2 were independent factors affecting the prognosis of esophageal squamous cell cancer patients.Conclusion Decreased expression of OTUD3 and increased expression of ILF2 in esopha-geal squamous cell cancer tissues are implicated in the malignant progression of esophageal squamous cell cancer and serve as independent factors affecting patient outcomes.
6.A novel intracoronary hypothermia device reduces myocardial reperfusion injury in pigs
Zhiqiang PEI ; Jin QIU ; Yongchao ZHAO ; Shuai SONG ; Rui WANG ; Wei LUO ; Xingxing CAI ; Bin LIU ; Han CHEN ; Jiasheng YIN ; Xinyu WENG ; Yizhe WU ; Chenguang LI ; Li SHEN ; Junbo GE
Chinese Medical Journal 2024;137(20):2461-2472
Background::Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury.Methods::This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes ( n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion which was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group ( n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls ( n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (five and 42 days post-MI) and a series of biomarkers/histological studies were performed. Results::The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH.Conclusions::The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.
7.Effects of Content of Alkaloids in Aconiti Kusnezoffii Radix with Different Degrees of Processing on Vagus Nerve Action Potential and Electrocardiogram in Rats
Wenhui LI ; Wei GAO ; Liangliang SONG ; Wenting ZU ; Jiasheng WANG ; Hongyue WANG ; Jing WANG ; Ying ZHAO ; Ziqin LIU ; Liyuan BAO ; Hong DU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(12):129-135
Objective To compare the contents of alkaloid in Aconiti Kusnezoffii Radix with different degrees of processing and their effects on electrocardiogram and vagus nerve action potential in SD rats;To establish a toxicity evaluation method for Aconiti Kusnezoffii Radix and its processed products.Methods HPLC was used to determine the contents of six alkaloid components,including benzoyl neoaconitine,benzoyl aconitine,benzoyl subeaconitine,neoaconitine,subeaconitine and aconitine in Aconiti Kusnezoffii Radix and Aconiti Kusnezoffii Radix Cocta of soaking and boiled for 30 minutes,boiled for 4 h without soaking,soaking and boiled for 4 h,and soaking and boiled for 8 h.SD rats were subjected to sublingual drainage with Aconiti Kusnezoffii Radix and four types of processed products.The vagus nerve action potential and electrocardiogram of rats before and after administration were recorded,and the correlation analysis between alkaloid content and vagus nerve action potential and heart rate was conducted.Results The contents of alkaloid of the four processed products showed that the content of diester alkaloids was soaking and boiled for 30 min>boiled for 4 h without soaking>soaking and boiled for 4 h>soaking and boiled for 8 h;monoester alkaloid content:boiled for 4 h without soaking>soaking and boiled for 30 min>soaking and boiled for 4 h>soaking and boiled for 8 h.After the administration of each sample,compared with the basal discharge,the vagus nerve discharge of rats with different processed products was changed by sublingual administration,heart rate increased,the degree of arrhythmia increased,and it varied with the degree of processing;the results of correlation analysis showed that there was a significant correlation between the nerve discharge area and the contents of diester alkaloids and total alkaloids.Conclusion The action potential of the vagus nerve and electrocardiogram of rats after sublingual drainage administration can reflect the degree of numbness in the tongue,which can provide reference for the study of tongue sensation of Aconiti Kusnezoffii Radix.
8.Preparation, properties and antibacterial applications of medical nano-metals and their oxides: a review.
Jiasheng ZUO ; Ying QIN ; Zuzhen ZHAO ; Lu XING ; Tian LIU ; Song WANG ; Weiqiang LIU
Chinese Journal of Biotechnology 2023;39(4):1462-1476
Antibiotics are playing an increasingly important role in clinical antibacterial applications. However, their abuse has also brought toxic and side effects, drug-resistant pathogens, decreased immunity and other problems. New antibacterial schemes in clinic are urgently needed. In recent years, nano-metals and their oxides have attracted wide attention due to their broad-spectrum antibacterial activity. Nano-silver, nano-copper, nano-zinc and their oxides are gradually applied in biomedical field. In this study, the classification and basic properties of nano-metallic materials such as conductivity, superplasticity, catalysis, and antibacterial activities were firstly introduced. Secondly, the common preparation techniques, including physical, chemical and biological methods, were summarized. Subsequently, four main antibacterial mechanisms, such as cell membrane, oxidative stress, DNA destruction and cell respiration reduction, were summarized. Finally, the effect of size, shape, concentration and surface chemical characteristics of nano-metals and their oxides on antibacterial effectiveness and the research status of biological safety such as cytotoxicity, genotoxicity and reproductive toxicity were reviewed. At present, although nano-metals and their oxides have been applied in medical antibacterial, cancer treatment and other clinical fields, some issues such as the development of green preparation technology, the understanding of antibacterial mechanism, the improvement of biosafety, and the expansion of application fields, require further exploration.
Oxides/chemistry*
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Metal Nanoparticles/chemistry*
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Anti-Bacterial Agents/chemistry*
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Zinc
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Copper
9.Current situation and development strategy of health emergency standardization system
Jiasheng XIONG ; Huanyu WU ; Qi ZHAO
Shanghai Journal of Preventive Medicine 2022;34(5):491-498
In recent years, the increasing scale and scope of public health emergencies have brought serious challenges to China's health emergency system. It is in urgent need to develop the existing health emergency system toward the goal of multi-industry, multi-discipline, multi-professional and multi-regional, while the concept of standardization is essential to achieve this goal. This article describes the construction process of health emergency standardization system by the World Health Organization, the International Organization for Standardization, the United States, and China; analyzes the problems of China's health emergency standardization system by comparing the system between China and the United States, proposes the construction dimensions of China's health emergency standard system, and suggests development strategies targeting the shortcomings of China's health emergency standardization.

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