1.Role of the iNOS/IRS1/AKT/GSK-3β signaling pathway in chronic intermittent hypoxia-induced insulin resistance
Meina Jin ; Xueli Zhou ; Haibo Li ; Wei Bai ; Chuxuan Jia ; Li Gao ; Lijue Ren ; Qingyu Chen ; Rui Wang ; Hua Li ; Cuiying Wei
Acta Universitatis Medicinalis Anhui 2025;60(2):210-217
Objective :
To pathological changes and inducible nitric oxide synthase(iNOS), phosphorylated insulin receptor substrate 1 serine 307(p-IRS1ser 307), phosphorylated protein kinase B serine 473(p-AKTser 473), glycogen synthase kinase-3β(GSK-3β), and gluconeogenic synthase(GS) proteins were observed in the liver of rats under the condition of chronic intermittent hypoxia-replicated oxygen in control. And to explore the role of iNOS/IRS1/AKT/GSK-3β signaling pathway in chronic intermittent hypoxia-induced insulin resistance.
Methods :
Forty SD rats were randomly divided into a control group(NC group) and an experimental group(CIH group), with 20 rats in each group. The NC group was placed in a normoxic environment for 12 weeks, while the CIH group was first subjected to intermittent hypoxia for 8 weeks, and then resumed normoxic rearing until the 12th week. Fasting blood glucose(FBG) and fasting insulin(FINS) were measured at baseline, week 8 and week 12, and liver tissues were taken for pathology and measurement of iNOS, p-IRS1ser 307, p-AKTser 473, GSK3β and GS levels, to compare the differences between groups.
Results:
t baseline, there was no significant difference in liver pathology between the two groups, and the observed indexes were not statistically significant(P>0.05); at 8 weeks, compared with the NC group, liver pathology in the CIH group showed significant disorganization of hepatic blood sinusoids and hepatocyte cords, obvious hepatocyte edema, smaller nuclei, increased lymphocyte infiltration, and a small number of fat vacuoles, significantly higher levels of FBG, FINS, insulin resistance index(HOMA-IR), iNOS mRNA, p-IRS1ser 307 protein, GSK-3β protein levels, and decreased p-AKTser 473 protein and GS protein levels, all of which were statistically significant(allP<0.05). IRS1ser 307 protein, GSK-3β protein levels were increased, p-AKTser 473 protein and GS protein levels were decreased, and the differences were statistically significant(allP<0.05); at 12 weeks, no lymphocyte infiltration was seen in the CIH group compared with that of the NC group and fat vacuoles significantly increased, and there was no improvement in the other pathological damage that had already occurred, and the levels of p-AKTser 473 protein significantly increased. AKTser 473 protein level significantly increased, p-IRS1ser 307 protein and GS protein levels were significantly reduced, all of which were statistically significant(allP<0.05), and the rest of the observational indexes were not statistically significant. Pearson′s correlation analysis showed that HOMA-IR of CIH group was significantly positively correlated with the levels of iNOS mRNA, p-IRS1ser 307 protein, and GSK-3β protein at 8 weeks(r=0.874, 0.817,0.872;allP<0.05), and significantly negatively correlated with the levels of p-AKTser 473 protein and GS protein(r=-0.886,-0.879;allP<0.05).
Conclusion
Chronic intermittent hypoxia can lead to hepatic pathological damage that cannot be reversed even by reoxygenation interventions and may mediate the development of insulin resistance by upregulating the IRS1/AKT/GSK-3β signaling pathway through the upregulation of iNOS mRNA expression.
2.Health economic evaluation of minimally invasive surgery in treatment of digestive tract cancers: a Meta-analysis
Xiaoyue YIN ; Ning ZHOU ; Xueli YANG ; Zhuoyu SUN ; Yinghui BAO ; Shengshu WANG ; Ke HAN ; Jing LONG ; Min ZHAO ; Haowei LI ; Rongrong LI ; Shimin CHEN ; Junhan YANG ; Huaihao LI ; Yueting SHI ; Guoning ZHU ; Jianhua WANG ; Shanshan YANG ; Boyan LI ; Wenchang WANG ; Shengyan DU ; Yao HE ; Enqiang LING-HU ; Huikai LI ; Miao LIU ; Juan XIE
Chinese Journal of Epidemiology 2025;46(1):154-165
Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.
3.Impact of spinal sagittal balance on reinforced vertebral recompression fractures following percutaneous kyphoplasty
Lide TAO ; Huajian SHAN ; Jun DAI ; Jinyu BAI ; Wentao ZHONG ; Chaowen BAI ; Xueli QIU ; Xiaozhong ZHOU ; Bingchen SHAN
Chinese Journal of Orthopaedics 2025;45(15):977-983
Objective:To investigate the correlation between postoperative spinal sagittal parameters and reinforced vertebral recompression fractures in patients with osteoporotic vertebral compression fractures (OVCFs) who have undergone percutaneous kyphoplasty (PKP).Methods:Data on patients with OVCFs treated with PKP at the Department of Orthopaedics, Second Affiliated Hospital of Soochow University, from August 2020 to August 2024, were collected. Among these, 31 patients who underwent single-segment PKP experienced postoperative reinforced vertebral recompression fractures (recompression fracture group), comprising 8 males and 23 females, with a mean age of 73.74±8.76 years, a body mass index (BMI) of 23.83±1.87 kg/m 2, and a bone mineral density T-value of -2.29±0.55. The remission rate of the visual analogue scale (VAS) after surgery was 80.14%±4.86%, with a mean volume of bone cement used at 5.37±0.69 ml. The surgical segments involved included T 5 (1 case), T 8 (1 case), T 10 (1 case), T 11 (4 cases), T 12 (9 cases), L 1 (7 cases), L 2 (4 cases), L 3 (2 cases), and L 4 (2 cases). Following a 1∶1 matching principle, 31 patients whose vertebrae did not experience reinforced recompression fractures during the same period (non-recompression fracture group) were included. This group also comprised 8 males and 23 females, with a mean age of 74.88±8.31 years, a BMI of 23.15±2.04 kg/m 2, a bone mineral density T-value of -2.76±0.64, and a VAS remission rate of 79.75%±5.01%. The mean volume of bone cement used in this group was 5.41±0.72 ml. The surgical segments involved included T 8 (1 case), T 10 (1 case), T 11 (4 cases), T 12 (8 cases), L 1 (7 cases), L 2 (5 cases), L 3 (2 cases), L 4 (2 cases), and L 5 (1 case). There were no statistically significant differences in the aforementioned indicators between the two patient groups ( P>0.05). A comparison of the postoperative spinal sagittal parameters between the two groups was conducted, focusing on the local kyphosis angle (LKA), lumbar lordosis (LL), thoracic kyphosis (TK), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and the lumbar-pelvic matching value (PI-LL). Indicators that exhibited statistically significant differences were included in the binary logistic regression analysis to evaluate the impact of spinal sagittal parameters following PKP on the recompression of the reinforced vertebral. Results:The time to reinforced vertebral recompression fractures after PKP ranged from 35 to 184 d, with a median of 69 d. The TK in the recompression fracture group (46.56°±7.02°) was significantly greater than that in the non-recompression fracture group (41.95°±5.76°). Additionally, the LKA, PI and SS were all smaller in the recompression fracture group (9.84°±2.13°, 41.36°±4.27°, 22.69°±5.53°, respectively) compared to the non-recompression fracture group (12.37°±2.64°, 48.09°±6.33°, 28.41°±7.64°), with all differences being statistically significant ( P<0.05). However, no significant differences were observed between the LL, PT, and PI-LL values ( P>0.05). TK, LKA, PI, and SS were included in the binary logistic regression analysis, which indicated that TK [ OR=1.533, 95% CI(1.47, 1.59)] after PKP was positively correlated with the occurrence of reinforced vertebral recompression fractures. Conversely, LKA [ OR=0.882, 95% CI(0.80, 0.96)], PI [ OR=0.815, 95% CI(0.71, 0.91)], and SS [ OR=0.833, 95% CI(0.73, 0.93)] were negatively correlated. Conclusions:The incidence of reinforced vertebral recompression fractures following PKP is associated with spinal sagittal parameters, including TK, LKA, PI, and SS. Specifically, a larger TK and smaller values of LKA, PI, and SS are correlated with an elevated risk of reinforced vertebral recompression fractures.
4.Toxicity and sublethal effects of calcium cyanamide against susceptible strains of Aedes albopictus
Luyang ZHENG ; Huiyi XU ; Qingqiu WEN ; Ning ZHOU ; Xueli ZHENG
Chinese Journal of Schistosomiasis Control 2025;37(2):196-200
Objective To examine the toxicity and sublethal effects of calcium cyanamide against susceptible isolates of Aedes albopictus, so as to provide insights into rational use of calcium cyanamide for integrated management of Ae. albopictus. Methods The sublethal concentrations [30% lethal concentration (LC30) and median lethal concentration (LC50)] of calcium cyana mide against susceptible strains of Ae. albopictus were determined using the larval immersion test. With 100 mL of dechlorinated water as the control group, after the larvae of susceptible strains of Ae. albopictus were immersed in calcium cyanamide for 24 hours, the pupation rate, pupation duration, emergence rate, number of eggs laid, percentage of eggs hatched, and lifespan of Ae. albopictus were calculated and compared post-treatment with calcium cyanamide at different sublethal concentrations. The midgut tissues of larvae of susceptible strains of Ae. albopictus treated with 100 mg/L calcium cyanamide were sampled for pathological sectioning to observe midgut tissue damages. To evaluate the residual activity, 100 larvae of susceptible strains of Ae. albopictus were treated with 200 mg/L and 500 mg/L calcium cyanamide, and the mortality of larvae was calculated every 24 hour, with dead larvae replaced until no larval death. Results The regression equation for the toxicity of calcium cyanamide against larvae of susceptible strains of Ae. albopictus was y = -9.441 + 4.657x, with an LC50 of 106.42 mg/L [95% confidence interval (CI): (94.64, 118.36) mg/L] and an LC30 of 82.17 mg/L [95% CI: (94.64, 118.36) mg/L], respectively. After larvae of susceptible strains of Ae. albopictus were treated with sublethal concentrations (LC30 and LC50) of calcium cyanamide for 24 hours, there were reduced pupation and emergence rates of larvae (all P values < 0.000 1), prolonged pupal stage (both P values < 0.000 1), reduced numbers of eggs laid by survival female Ae. albopictus (both P values < 0.000 1), reduced percentages of eggs hatched by Ae. albopictus eggs (both P values < 0.000 1), and reduced median survival period of survival female Ae. albopictus (χ2 = 9.36 and 20.33, both P values < 0.01) in the LC30 and LC50 groups relative to the control group. There was a numerical decline in the median survival period of survival female Ae. albopictus in the LC30 groups relative to the control group (χ2 = 2.42, P > 0.05), and there was a significant decline in the median survival period of survival female Ae. albopictus in the LC50 group relative to the control group (χ2 = 11.42, P < 0.01). Histopathological examinations showed severe damages to the midgut tissues of larvae of susceptible strains of Ae. albopictus, and residual activity assay revealed that the mortality of larvae of susceptible strains of Ae. albopictus was both 0 on day 32 post-treatment with calcium cyanamide at a concentration of 200 mg/L and on day 70 post-treatment with calcium cyanamide at a concentration of 500 mg/L, showing complete loss of the larvicidal activity of calcium cyanamide. Conclusions Calcium cyanamide is highly toxic against susceptible strains of Ae. albopictus, and calcium cyanamide at sublethal concentrations (LC30 and LC50) may inhibit growth, development, and reproductive capability of susceptible strains of Ae. albopictus, and shorten the lifespan of adult mosquitoes.
5.Bibliometrics analysis of wound healing after tooth extraction
Xueli WAN ; Xiaorong ZHOU ; Wenqiang JIANG ; Yanjun DIAO ; Xian LIU ; Yongle SHI
Journal of Practical Stomatology 2025;41(1):118-125
Tooth extraction is one of the most common procedures in oral surgery.Poor wound healing is a common problem after tooth extraction.Poor wound healing may not only lead to eating difficulties and impaire psychological health,but also increase the difficulty and cost of treatment,prolong the treatment period and lead to osteonecrosis of the jaw in severe cases.Currently,there is a lack of systematic integration and evaluation of domestic and international studies related to post-extraction wound healing.In this study VOSviewer,Bibliometrix and CiteSpace software were used to econometrically analyse the literature on post-extraction wound healing from 2013 to 2023,with the aim of providing a reference for developing more scientific and systematic strategies for post-ex-traction wound management and prevention of the complications.
6.GSTP1-mediated inhibition of ACSL4-dependent ferroptosis via JNK pathway in DOX-induced cardiomyopathy.
Mingbo WU ; Ye ZHAO ; Dong LI ; Xueli HU ; Jiaojiao ZHOU ; Siyi CHEN ; Xin YANG ; Zegang LI ; Xiaomiao RUAN ; Jingwen YANG ; Wenwu LING
Chinese Medical Journal 2025;138(19):2498-2510
BACKGROUND:
Doxorubicin hydrochloride (DOX) is extensively used in the treatment of various tumors. However, its clinical application is limited due to dose-dependent cardiotoxicity. Currently, few effective strategies exist to mitigate or eliminate DOX-induced cardiomyopathy (DIC). Although ferroptosis is implicated in DIC and its inhibition partially alleviates the condition, the direct targets of DOX in the progression of cardiotoxicity remain unclear. This study aimed to discover the direct targets of DOX in ferroptosis-mediated DIC.
METHODS:
A DOX pulldown assay was performed to identify proteins specifically binding to DOX in murine hearts, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify candidate proteins. A cardiac injury mouse model was established by DOX treatment. Based on this, multiple ferroptosis biomarkers were detected by flow cytometry, quantitative real-time polymerase chain reaction, western blotting, immunochemistry, etc. Besides, specific activator and inhibitor of signaling pathways were applied to illuminate molecular mechanisms.
RESULTS:
Glutathione S-transferase P1 (GSTP1) was identified as a DOX target. GSTP1 activity was inhibited in DOX-treated cardiomyocytes, while its overexpression significantly alleviated DIC. Moreover, GSTP1 overexpression inhibited acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. Mechanistically, GSTP1 overexpression suppressed c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing reactive oxygen species (ROS) production and inhibiting ferroptosis in DIC.
CONCLUSIONS
This study identifies the DOX/GSTP1/JNK axis as a critical pathway mediating ACSL4-dependent ferroptosis in DIC. GSTP1 is highlighted as a potential key mediator of ferroptosis and a promising therapeutic target for DIC.
7.Journey map of health management for patients with disability caused by accidental trauma from the perspective of social ecosystem theory
Hengchang CAO ; Lili JIANG ; Yangchun ZHANG ; Feng CHEN ; Zheng ZHOU ; Xueli JI
Chinese Journal of Modern Nursing 2025;31(35):4761-4769
Objective:To develop a journey map for health management of patients with disability caused by accidental trauma from the social ecosystem theory perspective, so as to gain deeper insights into their actual needs during medical treatment and rehabilitation.Methods:The descriptive qualitative research was adopted. Purposeful sampling was employed to select patients with disability caused by accidental trauma admitted to the Trauma Center of the Department of Emergency and Critical Care Medicine at the First Affiliated Hospital with Nanjing Medical University between April and May 2024 for semi-structured interviews. Traditional content analysis method was employed to analyze the interview data.Results:From three dimensions of microsystem, mesosystem, and macrosystem, the needs and potential issues of medical treatment at different stages of the health management process for patients with disability caused by accidental trauma were analyzed, forming a patient journey map.Conclusions:Patients with disability caused by accidental trauma face prolonged periods of medical treatment, rehabilitation, and lifestyle readjustment, imposing significant burdens on themselves, their caregivers, and their families. Healthcare providers may proactively engage with patients based on their current and potential issues and needs, offer specialized guidance at critical junctures and meet the need of patients for continuity of care, thereby improving patients' quality of life and overall health outcomes.
8.Determination of Three Stereoisomers in Baloxavir Marboxil by Reversed-phase HPLC
Kai SHI ; Kai YAN ; Ting SUN ; Xue FENG ; Fugang ZHOU ; Yuxia HE ; Xueli LIU ; Jialiang ZHU
Herald of Medicine 2025;44(4):633-638
Objective To establish a reversed-phase HPLC method for determining three stereoisomers in baloxavir marboxil and provide a basis for the quality specification of baloxavir marboxil.Methods The chromatographic column was CHIRALPAK IC-3(4.6 mm × 150 mm,3 μm),The mobile phase was acetonitrile-0.1%formic acid aqueous solution-isopropanol(35:50:15).The column temperature was 40 ℃.The flow rate was 0.5 mL·min-1.The injection volume was 10 μL.The detection wavelength was 259 nm.Result The isomer peaks were completely separated from the principal component peak.The detection limits for stereoisomers 1,2 and 3 were 0.024 7,0.038 7,0.038 1 μg·mL-1 respectively.The quantitation limits for stereoisomers 1,2 and 3 were 0.049 4,0.077 3,0.076 1 μg·mL-1 respectively.There were good linear relationships between the concentrations and peak area within the ranges of the study,and the linearity concentration ranges of stereoisomers 1,2 and 3 were 0.049 5-0.989 0 μg·mL-1,0.051 6-1.031 0 μg·mL-1,0.050 8-1.015 0 μg·mL-1 respectively.The linear correlation coefficients were 0.999 4.The recovery was 92.28%-103.90%.The sample solution was stable in 48 h at room temperature.Conclusion The method is accurate and reliable for determining stereoisomers in baloxavir marboxil,and provide a guideline of quality standards of baloxavir marboxil and safety evalution.
9.Bibliometrics analysis of wound healing after tooth extraction
Xueli WAN ; Xiaorong ZHOU ; Wenqiang JIANG ; Yanjun DIAO ; Xian LIU ; Yongle SHI
Journal of Practical Stomatology 2025;41(1):118-125
Tooth extraction is one of the most common procedures in oral surgery.Poor wound healing is a common problem after tooth extraction.Poor wound healing may not only lead to eating difficulties and impaire psychological health,but also increase the difficulty and cost of treatment,prolong the treatment period and lead to osteonecrosis of the jaw in severe cases.Currently,there is a lack of systematic integration and evaluation of domestic and international studies related to post-extraction wound healing.In this study VOSviewer,Bibliometrix and CiteSpace software were used to econometrically analyse the literature on post-extraction wound healing from 2013 to 2023,with the aim of providing a reference for developing more scientific and systematic strategies for post-ex-traction wound management and prevention of the complications.
10.Journey map of health management for patients with disability caused by accidental trauma from the perspective of social ecosystem theory
Hengchang CAO ; Lili JIANG ; Yangchun ZHANG ; Feng CHEN ; Zheng ZHOU ; Xueli JI
Chinese Journal of Modern Nursing 2025;31(35):4761-4769
Objective:To develop a journey map for health management of patients with disability caused by accidental trauma from the social ecosystem theory perspective, so as to gain deeper insights into their actual needs during medical treatment and rehabilitation.Methods:The descriptive qualitative research was adopted. Purposeful sampling was employed to select patients with disability caused by accidental trauma admitted to the Trauma Center of the Department of Emergency and Critical Care Medicine at the First Affiliated Hospital with Nanjing Medical University between April and May 2024 for semi-structured interviews. Traditional content analysis method was employed to analyze the interview data.Results:From three dimensions of microsystem, mesosystem, and macrosystem, the needs and potential issues of medical treatment at different stages of the health management process for patients with disability caused by accidental trauma were analyzed, forming a patient journey map.Conclusions:Patients with disability caused by accidental trauma face prolonged periods of medical treatment, rehabilitation, and lifestyle readjustment, imposing significant burdens on themselves, their caregivers, and their families. Healthcare providers may proactively engage with patients based on their current and potential issues and needs, offer specialized guidance at critical junctures and meet the need of patients for continuity of care, thereby improving patients' quality of life and overall health outcomes.


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