1.Identification of a JAK-STAT-miR155HG positive feedback loop in regulating natural killer (NK) cells proliferation and effector functions.
Songyang LI ; Yongjie LIU ; Xiaofeng YIN ; Yao YANG ; Xinjia LIU ; Jiaxing QIU ; Qinglan YANG ; Yana LI ; Zhiguo TAN ; Hongyan PENG ; Peiwen XIONG ; Shuting WU ; Lanlan HUANG ; Xiangyu WANG ; Sulai LIU ; Yuxing GONG ; Yuan GAO ; Lingling ZHANG ; Junping WANG ; Yafei DENG ; Zhaoyang ZHONG ; Youcai DENG
Acta Pharmaceutica Sinica B 2025;15(4):1922-1937
The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.
2.The mechanism of the effects of bisphenol A and high-fat diet on non-alcoholic fatty liver disease in mice
Yunfeng LIN ; Jiaoxiang ZHANG ; Zhilin ZHANG ; Zeqi LU ; Ruijuan YAO ; Lanlan XU ; Congzheng QI ; Lili LIU ; Qiansheng HU ; Wei ZHU
China Occupational Medicine 2025;52(4):376-385
Objective To explore the effects of combined exposure to bisphenol A (BPA) and high-fat diet on liver lipid metabolism and hepatocyte senescence in mice, and to elucidate the potential mechanisms of the onset and development of non-alcoholic fatty liver disease (NAFLD). Methods Specific pathogen free C57BL/6J mice were randomly divided into six groups, with 10 mice with equal numbers of each sex in each group. The mice in the control group and the simple BPA group were fed with regular diet, while others four groups of mice were fed with high-fat diet. At the same time, the mice in the simple BPA group were intragastric administered with BPA at a dose of 50 μg/kg body weight, while the mice in the low-, medium- and high-dose BPA+high-fat groups were intragastric administered with BPA at doses of 5, 50 and 500 μg/kg body weight respectively. The mice in the control group and the high-fat group were intragastric administered with the same volume of corn oil once per day for 90 consecutive days. Liver tissues were subjected to hematoxylin-eosin (HE) and Oil Red O staining. Liver coefficients and lipid-stained area ratios were calculated. Serum level of total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, and the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined using an automatic biochemical analyzer. The hepatic tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 levels were quantified by enzyme-linked immunosorbent assay. The relative expression of cholesterol regulatory element binding protein 1 (SREBP1), CCAAT enhancer binding protein α, P16, and phosphorylated histone H2AX (γ-H2AX) in liver tissues was detected using Western blotting. The interaction effect of the combined exposure to BPA and high-fat diet was observed based on the result of mice in the control group, the simple high-fat group, the simple BPA group, and the medium-dose BPA group+high-fat group (the combined exposure group) using a 2×2 factorial design. The results of mice in the simple high-fat group and the low-, medium-, and high-dose BPA+high-fat groups were used to observe the effect of BPA exposure dose under high-fat diet conditions. Results i) The interactive effect of combined exposure to BPA and high fat. The HE and Oil Red O staining results indicated that the combined exposure to BPA and high-fat diet successfully established NAFLD in mice. The interactive effect of combined exposure to BPA and high-fat diet on serum ALT activity and the relative expression of P16 in the liver tissue of female mice, as well as the serum ALT and AST activities and the relative expression of SREBP1 in the liver tissue of male mice was significant (all P<0.05). Specifically, the serum ALT activity of male mice in the combined exposure group was higher than that in the simple high-fat group (P<0.05), while the ALT activity in the serum of female mice in the combined exposure group was lower than that in the simple BPA group (P<0.05). The relative expression of SREBP1 protein in the liver tissue of male mice in the combined exposure group was higher than that in the control group, the simple high-fat group, and the simple BPA group (all P<0.05). For the other indicators, there were no significant differences in the interactive effect of combined exposure to BPA and high-fat diet (all P>0.05). ii) Dose effects of BPA exposure. The HE and Oil Red O staining result showed that the degree of vacuolar steatosis in the liver of female and male mice of medium- and high-dose BPA + high-fat groups was aggravated, and the range of inflammatory cell infiltration was expanded when compared with same-sex mice in the simple high-fat group. The serum ALT activity and the fat stained area ratio, as well as the relative expression of P16 in liver tissue of female mice in high-dose BPA + high-fat group increased (all P<0.05), while the level of IL-10 in liver tissue decreased (P<0.05), compared with the female mice in simple high-fat group. The serum ALT activity, the TNF-α level in liver tissue, and the relative expression of SREBP1, P16 and γ-H2AX proteins in liver tissue of male mice in high-dose BPA + high-fat group increased (all P<0.05), while the IL-6 level in liver tissue decreased (P<0.05), compared with the male mice in simple high-fat group. For the female or male mice in the low- and medium-dose BPA + high-fat groups, only some of the above indicators showed significant changes (all P<0.05). Conclusion The combined exposure to BPA and high-fat diet has a synergistic effect on the onset and development of NAFLD. The mechanism may be related to inducing cellular senescence and modulation of lipid synthesis pathways, thereby affecting liver steatosis. The exposure dose of BPA may affect the synergistic effect.
3.A comparative study with real-world data of different surgery for lung malignancies in the context of DRG payment
Yuanlin WU ; Yao LIU ; Lanlan GAN ; Guiyuan XIANG ; Chen LI ; Shigeng CHEN ; Qiuwan XIAN
Chongqing Medicine 2024;53(11):1645-1649
Objective To compare the safety,effectiveness and affordability of robotic-assisted thoracic surgery and video-assisted thoracic surgery in the treatment of malignant pulmonary tumors,and provide ref-erences for the management of selection of different surgical strategies for malignant pulmonary tumors in hospitals and medical insurance departments.Methods The medical records homepages and information sys-tem data of patients with malignant pulmonary tumors who underwent major thoracic surgery in this hospital and discharged from January 1 to December 31,2022 were obtained.The patients were divided into the robotic-assistedthoracic surgery group and video-assisted thoracic surgery group according to the surgical methodolo-gies.After performing propensity score matching (PSM),no statistically significant difference was observed in baseline data between the two groups (117 cases in each group).Then the indicators of safety,effectiveness and affordability were compared between the two groups.Results Concerning the safety,the postoperative in-cision infection rate in the robotic-assisted thoracic surgery group was significantly lower than that in the vide-o-assisted thoracic surgery group (P<0.05),and the amount of intraoperative blood loss and postoperative complication rate were not significantly different between the two groups (P>0.05).Regarding the effective-ness,the average surgical duration in the robotic-assisted thoracic surgery group was appreciably shorter than that in the video-assisted thoracic surgery group (P<0.05),no patient in the two groups was converted to open thoracotomy,and there was no statistically significant difference in the average length of hospital stay and postoperative hospital stay between the two groups (P>0.05).With regard to the affordability,the aver-age inpatient expenditure per case and average daily inpatient expenditure per case in the robotic-assisted tho-racic surgery group were significantly higher than those in the video-assisted thoracic surgery group (P<0.05),and there were disparities in the cost structure between the two procedures.The medical cost,adminis-tration cost and consumables cost in the robotic-assisted thoracic surgery group were significantly higher than those in the video-assisted thoracic surgery group (P<0.05).The cost of medical technology in the robotic-assisted thoracic surgery group was significantly lower than that in the video-assisted thoracic surgery group (P<0.05).Conclusion Physicians should comprehensively consider the clinical efficacy and cost burden of patients when selecting the robotic-assisted thoracic surgery or the video-assisted thoracic surgery,and the monitoring and evaluation of the utilization of clinical robotic-assisted thoracic surgery should be strength-ened.
4.New progress in the first-line treatment of advanced hepatocellular carcinoma
Chuanhui ZHANG ; Dongyue YAO ; Siqi LIU ; Lanlan YANG ; Zhenjing JIN
Chinese Journal of Hepatology 2024;32(2):173-179
Hepatocellular carcinoma is a kind of cancer with a strong invasion, a high incidence rate and mortality, and a poor prognosis. At the time of diagnosis, most patients are already in the advanced stages of a tumor and have lost the chance for radical surgical treatment. Advanced hepatocellular carcinoma treatment has a gradual transition from systemic chemotherapy to targeted therapy, immunotherapy, and combination therapy, especially immune checkpoint inhibitor-based immunotherapy combination therapy, such as combination with bevacizumab monoclonal antibodies and other drugs, or combination with TACE, HAIC, radiotherapy, ablation, and other treatment methods. Combination therapy has significant synergistic effects and thus has already become a future treatment trend for hepatocellular carcinoma. An immunotherapy-based combination therapy plan will run through the whole process of systemic therapy, which is expected to bring better survival benefits to patients with hepatocellular carcinoma. This article reviews the latest research progress in aspects of the first-line treatment of advanced hepatocellular carcinoma.
5.Analysis of the grouping effect and hospitalization cost of patients with malignant proliferative disease in a hospital under DRG payment
Guiyuan XIANG ; Yuanlin WU ; Lanlan GAN ; Shigeng CHEN ; Yao LIU
China Pharmacy 2023;34(13):1637-1641
OBJECTIVE To analyze the grouping effect and composition of hospitalization costs for cases of patients with malignant proliferative disease under the diagnosis-related group (DRG) payment system, as well as any changes, in order to provide a basis for medical institutions to improve DRG payment-related measures, control drug costs, and for relevant departments to make decisions. METHODS The data of patients with malignant proliferative disease cases were collected from a “Third Grade Class A” hospital in 2021 and 2022, and the variation coefficient (CV) was used to evaluate the grouping of DRG. The structural variation degree and the new grey correlation analysis were used to study the structural variation of hospitalization cost and the correlation degree between the hospitalization cost and the cost of other items. RESULTS The overall reduction in variance (RIV) for the DRG group of patients with malignant proliferative disease was 79.36%; the CV of other groups were all lower than one except that the RW21 group was 1.09. Compared with 2021, the hospitalization cost for patients with malignant proliferative disease in 2022 decreased by 17.80%, and the decreases in management fees and drug costs were 32.15% and 21.30%, respectively, while the per capita medical expenses increased by 17.26%. The new grey correlation degree of drug cost decreased, but that of medical expenses increased. CONCLUSIONS Under the DRG payment system, hospitalization costs for patients with malignant proliferative disease in the sample hospital decrease, but the grouping efficiency of RW21 and other disease groups needs improvement, and the cost structure needs optimization.
6.Fluid management strategies for patients with severe blast injury
Minfei YANG ; Mengyun XU ; Yu KE ; Xiao LU ; Lanlan ZHANG ; Xiaoyue YAO
Chinese Journal of Practical Nursing 2023;39(14):1105-1109
Objective:To summarize the precision fluid management of patients with severe blast injury in the emergency intensive care unit, so as to help patients smoothly pass through the dangerous period and recover smoothly.Methods:Based on the experience of fluid management in 6 patients admitted to the Second Affiliated Hospital Zhejiang University School of Medicine in the tanker truck explosion on 14 June, 2020. The main measures included: fluid volume management and dynamic adjustment; assessment of intake, output and urine volume, and dynamic adjustment of infusion volume and speed; monitoring of pulmonary oxygenation and timely adjustment of fluid resuscitation strategies; monitoring indexes and providing nursing care strategies for fluid management.Results:Finally, among 6 patients with severe blast injury, 5 patients were discharged from the hospital with follow-up treatment after they suffered from the shock and infection phases and refined fluid management, 1 patient died due to severe injury and ineffective rescue.Conclusions:Adopting individualized, phased, and refined liquid management strategy has clinical significance for patients with severe blast injury to smoothly pass the risk period.
7.Exploration and construction of the new generation of intelligent ICU unit based on 5G and artificial intelligence technology
Xiaoxia HUANG ; Yao LI ; Haotian CHEN ; Jiaying TANG ; Xu WANG ; Qiang LI ; Fangmin GE ; Dong CHEN ; Yonghua CHU ; Jianping YE ; Lanlan WU ; Shuaifeng LÜ ; Mao ZHANG
Chinese Journal of Emergency Medicine 2021;30(10):1269-1273
Objective:To explore the new generation of intelligent ICU Unit based on 5G and artificial intelligence technology.Methods:This study was conducted at the Second Affiliated Hospital, Zhejiang University School of Medicine from May 2019 to August 2020. Based on a multidisciplinary team including medical, nursing, hospital management, clinical medical engineering, 5G technology, information technology, artificial intelligence technology, logistics service, etc, was assembled to intelligently design and reconstruct an intelligent ICU Unit of Emergency ICU.Results:Based on 5G technology, a new intelligent ICU unit environment was constructed to realize remote and high-speed interaction of multi-dimensional information in ICU, including intelligent assistance of remote monitoring, remote ward rounds, remote consultation and family visits. An intelligent hospital infection prevention and control system was established including automatic identification and alarm of hand hygiene and personal protection.Conclusions:The new generation of intelligent ICU unit combined with 5G and artificial intelligence technology has changed the mode of medical service for critically ill patients and improved the service level, which is worthy of further exploration and application.
8.Recent progress in advanced glycation end-products of gestational diabetes mellitus
Shiyu LIU ; Jiaxin FU ; Yibo MENG ; Lanlan PENG ; Hui CHEN ; Xue XIAO ; Yuan YAO
Chinese Journal of Endocrine Surgery 2018;12(4):345-347,352
Advanced glycation end-products (AGEs) are stable and toxic by-products of non-enzymatic metabolic reaction of proteins,lipids and nucleotides.The elevated serum AGEs level in pregnant women is strongly associated with hyperglycemia,oxidative stress and insulin resistance and may be one of the cause for the onset and development of the gestational diabetes mellitus(GDM).This review mainly focuses on the pathogenesis of AGEs and GDM.
9.The establishment and implementation of physique nursing clinic of Traditional Chinese Medicine
Lanlan CHEN ; Yiping WANG ; Xingfeng LU ; Li LIU ; Fei YAO ; Feng CHEN
Chinese Journal of Nursing 2018;53(5):584-587
In order to understand the patients' physique accurately,and formulate individualized conditioning scheme for patients with biased physique,our hospital established a new clinic called physique nursing clinic of Traditional Chinese Medicine (TCM) in August 2017,formed a series of corresponding rules and management regulations,and made clear the focus of the clinic and the work content of outpatient nurses.After implementation,the physique nursing clinic of TCM has achieved various goals:a total of 526 cases of TCM physique identification were carried out,324 patients with biased physique were given health guidance,and 148 cases of referral treatment.Hospital organized clinic members to go out to study for 10 times,and the voluntary community clinic were developed for 4 times.The physique nursing clinic of TCM has been appreciated by outpatients,doctors and nurses,who believed it could meet patients' individualized health needs and promote the development of TCM nursing.
10.Risk factors for progressive cardiogenic stroke
Lanlan CHEN ; Daihua TAO ; Jun XU ; Yao XU ; Hailong YU ; Tingting QIAO ; Li JIANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2018;20(1):50-54
Objective To study the risk factors for progressive cardiogenic stroke (CS).Methods Seventy-one acute ischemic stroke patients admitted to our hospital from 2008-08-01 to 2014-12-31 were divided into progressive CS group (n=14) and non-progressive CS group (n=57).The NIHSS was used to assess the neurologic deficit when the patients were admitted and 30 days after the stroke onset.Their clinical data were retrospectively analyzed.The risk factors for progressive CS were analyzed by univariate logistic regression analysis and multivariate logistic regression analysis respectively,their critical thresholds were analyzed according to the ROC curve.Results The NIHSS improvent of the progressive CS group was significantly less than that of the non-progressive CS group (P<0.01).The age was significantly older,the incidence of right-side infarction and the serum level of D-dimer were significantly higher while the serum level of glutamic pyruvic transaminase was significantly lower in progressive CS group than in non-progressive CS group (77.29±8.87 years vs 71.44±9.51 years,P=0.041;71.4% vs 33.3%,P=0.009;2.82 mg/L vs 0.91 mg/L,P=0.048;13.79±4.44 U/L vs 21.98±17.34 U/L,P=0.002).Lo gistic regression analysis showed a significant difference in age,right-side infarction and serum D-dimer level between the two groups (P=0.030,P=0.007,P=0.025).The area under the ROC curve revealed that age > 70.75 years and serum D-dimer level >1.23 mg/L were the risk factors for progressive CS.Conclusion Age,right-side infarction and serum D-dimer level are the risk factors for progressive CS and can thus be used as predictors of progressive CS.

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