1.Differences in deltamethrin resistance and kdr gene mutation in Culex tritaeniorhynchus population in and outside the Yellow Sea wetland
Xiao-er ZHANG ; Zhi-ming WU ; Ye TIAN ; Qian CUI ; Yu-qian JI ; Huan WANG ; Shu-juan YANG ; Yi-chao ZHAO ; Yu WANG ; Hua-yu YIN ; Yu DING ; Guo-jin YAN ; Min-sen ZHAO ; Shou-gang ZHANG ; Bing-dong SONG ; Hong-na CHEN ; Jian GAO ; Wei-fang YANG ; Yu-fu ZHANG ; Hui LIU ; Hong-liang CHU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):101-107
Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.
2.Spatiotemporal monitoring and ARIMA modeling of Blattella germanica populations in Nanjing, China (2017-2024)
Jian-jun XIA ; Pu-min ZHOU ; Yan ZHANG ; Bing-dong SONG ; Lu-yao SUN ; Shou-gang ZHANG
Acta Parasitologica et Medica Entomologica Sinica 2026;33(3):210-215
Objective Using cockroach surveillance data in Nanjing from 2017 to 2024, we have descriptively analyzed population characteristics and changes in insecticide resistance among Blattella germanica, and have established a seasonal Autoregressive Integrated Moving Average (ARIMA) model to predict monthly population densities in Nanjing spanning the year 2025. Methods B. germanica density and infestation rate were monitored using the sticky trap method, and insecticide resistance was assessed using the residual contact method. Our ARIMA model was applied to fit and estimate cockroach density fluctuations over time. Results From 2017 to 2024, B. germanica accounted for 94.90% of all cockroach specimens captured in Nanjing, with an average density of 0.37 cockroaches per trap and an average infestation rate of 5.56%. Significant differences in density and infestation rate were observed among different habitats (P<0.001). Significant downward annual trends in both density and infestation rate were found (P<0.05). ARIMA was found to be the optimal model for fitting the density data from 2017 to 2024 (0, 1, 1) × (0, 1, 1)1 2. Conclusions From 2017 to 2024, B. germanica was overwhelmingly the dominant cockroach species in Nanjing, with both its density and infestation rate declining annually. A positive correlation was observed between the amount and proportion of insecticide use and the development of insecticide resistance (P<0.05). The established model demonstrated good performance in predicting monthly B. germanica densities in Nanjing throughout 2025, providing a valuable reference for future surveillance and control efforts.
3.Risk-stratified outcomes of red blood cell transfusion in on-pump cardiac surgery.
Tianlong WANG ; Jing WANG ; Han ZHANG ; Qiaoni ZHANG ; Mingru ZHANG ; Gang LIU ; Shujie YAN ; Jian WANG ; Yuan TENG ; Bingyang JI
Chinese Medical Journal 2025;138(20):2678-2680
4.International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025).
Sheng-Sheng ZHANG ; Lu-Qing ZHAO ; Xiao-Hua HOU ; Zhao-Xiang BIAN ; Jian-Hua ZHENG ; Hai-He TIAN ; Guan-Hu YANG ; Won-Sook HONG ; Yu-Ying HE ; Li LIU ; Hong SHEN ; Yan-Ping LI ; Sheng XIE ; Jin SHU ; Bin-Fang ZENG ; Jun-Xiang LI ; Zhen LIU ; Zheng-Hua XIAO ; Jing-Dong XIAO ; Pei-Yong ZHENG ; Shao-Gang HUANG ; Sheng-Liang CHEN ; Gui-Jun FEI
Journal of Integrative Medicine 2025;23(5):502-518
Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy*
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Humans
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Medicine, Chinese Traditional/methods*
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Practice Guidelines as Topic
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Drugs, Chinese Herbal/therapeutic use*
5.Inhibitory effect and mechanism of active components of Alpinia katsumadai on tumor xenograft growth and tumor angiogenesis of human pancreatic cancer cells in nude mice
Gang LIANG ; Jianlin HUANG ; Jian WANG ; Dan ZHANG ; Minghua LIU
China Pharmacy 2025;36(24):3054-3059
OBJECTIVE To investigate the inhibitory effect and mechanism of the active components of Alpinia katsumadai (ACAK) on tumor xenograft growth and tumor angiogenesis of human pancreatic cancer PANC-1 cells in nude mice. METHODS A tumor xenograft model in nude mice was established using human pancreatic cancer PANC-1 cells. The mice were randomly divided into model control group (intragastric administration of 0.9% normal saline), solvent control group (intragastric administration of 0.5% carboxymethyl cellulose sodium), positive control group (intraperitoneal injection of 0.5% carboxymethyl cellulose sodium+bevacizumab suspension 5 mg/kg ), and ACAK 50, 100, and 200 mg/kg groups (intragastric administration of 0.5% carboxymethyl cellulose sodium+ACAK suspension 50, 100, 200 mg/kg). The administration was carried out for 5 consecutive days followed by a 2-day interval, and this cycle was repeated for a total duration of 28 days. The tumor volume (TV), relative tumor volume (RTV), and relative tumor proliferation rate (T/C) at various time points from day 1 to day 28 after drug administration were measured and calculated for each group of nude mice. After the drug administration, the tumor weights were measured, and microvessel density (MVD) in the tumor xenograft tissues of nude mice, as well as relative protein expression levels of vascular endothelial growth factor (VEGF) and its receptor [fas-like tyrosine kinase-1 (Flt-1), kinase insert domain receptor (KDR)] were detected. RESULTS On the 24th day of ACAK administration,compared with the model control group, the TV and RTV (except for ACAK 50 and 100 mg/kg groups) of nude mice in the positive control group and ACAK dose groups were significantly decreased (P<0.05 or P<0.01), and the T/C of ACAK dose groups showed a dose-dependent decrease; the microvascular distribution of nude mice in the positive control group and ACAK dose groups was relatively sparse, and the tumor weight (except for the ACAK 50 mg/kg group), MVD, and relative expression levels of VEGF, KDR, and Flt-1 in the tumor xenograft tissues were significantly reduced (P<0.05 or P<0.01). CONCLUSIONS ACAK has a good anti-pancreatic cancer effect, and its mechanism may be related to its inhibition of VEGF/ VEGFR signaling pathway, thereby inhibiting angiogenesis in pancreatic cancer.
6.Establishment of an evaluation system for conversion to laparotomy in laparoscopic cholecystectomy and exploration of surgical grading management
Nannan ZHANG ; Jinxing GUO ; Gang WU ; Hui YI ; Yuanhang ZHOU ; Zhiwei LIAO ; Qi HUANG ; Jian DONG
Journal of Surgery Concepts & Practice 2025;30(1):54-60
Objective To develop and validate a scoring system to predict the possibility of laparoscopic cholecystectomy (LC) conversion to laparotomy based on preoperative clinical data, and to establish a grading management model of surgery. Methods A retrospective analysis was conducted on the clinical data of 9 414 patients who underwent LC at Renhe Hospital and Huashan Hospital from June 2013 to June 2018. The patients were divided into two groups: the LC group (9 246 patients who successfully underwent LC) and the conversion to laparotomy group (168 patients who required conversion to open surgery). The data of two groups were compared, and the risk factors affecting conversion to laparotomy were screened out by single factor analysis of Chi-square test. Then, the risk factors were analyzed by multiple Logistic regression, and the pre-coefficient of each variable of the risk factors was assigned according to the established conversion to laparotomy possibility function. After calculating the score of each case, the difference in the actual conversion rate of each group was compared. The area under receiver operating characteristic (ROC) curve was calculated to evaluate the performance of the scoring system. According to the scoring system, LC surgical grading management model was created and verified. Results The following factors were identified as significant risk factors for conversion to laparotomy (P < 0.001): body temperature ≥ 38.5℃, frequency of acute cholecystitis ≥3 times, maximum thickness of gallbladder wall ≥ 5 mm, gallbladder neck stone incarceration, diameter of common bile duct ≥8 mm, and surgical experience ≤50 cases were the risk factors for conversion to laparotomy (P < 0.001). A score >3 points was associated with a high risk of conversion to laparotomy. Conclusions The LC scoring system and surgical grading management are reliable and effective tools for predicting and reducing the conversion rate of LC to laparotomy.
7.Sinapine alleviates lung tissue inflammation and mucus hypersecretion in asthmatic mice by inhibiting Notch2/Notch3-Hes1 signal pathway
Hongmei Tang ; Xiaoyun Wang ; Jian Wang ; Yun Zhang ; Zhibin Wang ; Xiefang Yuan ; Xing Wang ; Guofeng Xu ; Gang Qin ; Yuejiao Li
Acta Universitatis Medicinalis Anhui 2025;60(2):286-292
Objective :
To investigate the effects of sinapine on lung tissue inflammation and mucus hypersecretion in asthmatic mice.
Methods:
Eight-week-old female C57BL/6J mice were randomly divided into Control group, ovalbumin(OVA) group, Sinapine group, and Sinapine+OVA group. The asthmatic mice model were established by intraperitoneal injection of OVA combined with aluminum hydroxide [Al(OH)3] suspension and OVA nasal stimulation. One hour before OVA nasal stimulation, the mice in Sinapine+OVA group and Sinapine group were intraperitoneally injected with sinapine solution, and the mice in OVA group and Control group were treated with the same dose of 0.9% sodium chloride solution. 24 hours after the last OVA stimulation, the inflammation of lung tissue of mice were observed by HE staining; the mucus secretion were evaluated by PAS staining; the mRNA expression levels of Interleukin-4(IL-4), Interleukin-5(IL-5), Interleukin-13(IL-13), tumor necrosis factor-alpha(TNF-α), Mucin 5ac(Muc5ac), and the mRNA of the key genes of Notch pathway such as Notch receptor 1(Notch1), Notch receptor 2(Notch2), Notch receptor 3(Notch3), and hes family bHLH transcription factor 1(Hes1) in lung tissues were detected by real-time fluorescent quantitative PCR(RT-qPCR); the expression levels of Notch1, Notch2, Notch3 and Hes1 proteins were determined by Western blot.
Results :
Compared with Control group, the inflammation score and PAS score of lung tissues of mice in OVA group increased(P<0.001); the mRNA expression levels of IL-4, IL-5, IL-13, TNF-α, and Muc5ac of mice in OVA group were enhanced(P<0.05); the mRNA and protein expression levels of Notch2, Notch3, and Hes1 of mice in OVA group significantly increased(P<0.001), while there was no significant difference in the mRNA and protein expression levels of Notch1. Compared with OVA group, the inflammation score and PAS score of lung tissues of mice in Sinapine+OVA group decreased(P<0.001); the mRNA expression levels of IL-4, IL-5, IL-13, TNF-α, and Muc5ac of mice in Sinapine+OVA group were reduced(P<0.05); the mRNA and protein expression levels of Notch2, Notch3, and Hes1 of mice in Sinapine+OVA group were downregulated(P<0.05), while there was no significant difference in the mRNA and protein expression levels of Notch1.
Conclusion
Sinapine can alleviate the lung tissue inflammation and mucus hypersecretion in asthmatic mice, and its mechanism may be related to the inhibition of Notch2/Notch3-Hes1 signal pathway.
8.Application of Ammonia Solution Coprecipitation Method in Strontium Isotope Analysis
Wen-Gang LIU ; Shuang WEI ; Xiao-Wei ZHANG ; Jian ZHANG ; Hong-Ying ZHOU
Chinese Journal of Analytical Chemistry 2025;53(1):115-123
In the process of strontium(Sr)isotope analysis,the separation and purification of Sr are crucial for obtaining high-precision Sr isotope ratios.In this work,ammonia solution was used as a precipitating agent to initially separate and purify Sr from geological samples through coprecipitation,followed by the combination with cation-exchange resin to quickly and effectively obtain high-purity Sr components.The experimental conditions of ammonia coprecipitation reaction were optimized using typical high Rb/Sr ratio(mass ratio)standard sample JR-2.The results showed that using 3 mL of ammonia(1 mol/L)as the precipitating agent,at 120℃for 1 h,could effectively remove more than 90%of Rb,Na and K,with Sr recovery exceeding 95%.To verify the stability and applicability of this separation process,geological standard samples(JR-2,BCR-2,AGV-2,BHVO-2,GSP-2,W-2a)with different rock types and Rb/Sr ratios were practically validated.The results demonstrated that the coprecipitation process with ammonia solution removed more than 90%of Rb,Na and K,with Sr recovery greater than 95%.To further assess the applicability of this method for samples with high Rb/Sr ratios,Rb was added to the rhyolite standard material JR-2,adjusting its Rb/Sr ratio to 500.The results showed that this separation process could still effectively achieve the separation of Rb and Sr,and high-precision Sr isotope analysis results were successfully obtained by combining thermal ionization mass spectrometer(TIMS).Ammonia solution,as a precipitating agent,offered advantages such as low cost,low procedural blanks,simplicity,and a wide range of applicability.Therefore,the combination of ammonia solution coprecipitation and cation-exchange resin enabled rapid Sr purification from geological samples,providing a novel separation approach for high-precision Sr isotope analysis of samples with high Rb/Sr ratios,with broad application prospects.
9.Effect of demethylation on the expression of miR-5194 and the biological function of miR-5194 in bladder cancer cells
Gang LIU ; Tingting ZHANG ; Dingwen GUI ; Xifeng WANG ; Jian ZHA
International Journal of Surgery 2025;52(2):118-122
Objective:To study the methylation level of miR-5194 promoter in bladder cancer tissues, and explore the effects of miR-5194 on the proliferation and migration of bladder cancer cells by targeting p21-activated protein kinase 2 (PAK2).Methods:The methylation level of miR-5194 promoter in bladder cancer tissues was analyzed using MethHC database. Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-5194 in bladder cancer MGH-U3, EJ, J82, and UMUC3 cells. 5-aza-2′-deoxycytidine (5-Aza-CdR) was used to treat bladder cancer cell lines, and RT-qPCR was used to detect the changes in the expression of miR-5194 in bladder cancer cell lines after 5-Aza-CdR treatment. UMUC3 cells were divided into miR-5194 group and NC group, and miR-5194 or miR-NC were transfected into UMUC3 cells, respectively. Colony formation assay and scratch assay were used to detect the effect of overexpression of miR-5194 on the proliferation and migration of UMUC3 cells. The bioinformatics tool miRGator and dual-luciferase reporter gene experiments verified the targeting relationship between miR-5194 and PAK2. The effect of overexpression of miR-5194 on the expression of PAK2 mRNA in UMUC3 cells was detected by RT-qPCR. The effect of overexpression of miR-5194 on the expression of PAK2 protein, proliferation-related proteins (CDK1, Cyclin B) and migration-related proteins (FOXC2, E47) in UMUC3 cells was detected by Western blotting. The measurement data were expressed as mean ± standard deviation ( ± s), the independent sample t-test was used for comparison between two groups, and one-way analysis of variance was used for comparison among multiple groups. Results:The methylation level of miR-5194 promoter in bladder cancer tissues was significantly higher than that in adjacent tissues ( P<0.01). Compared with the immortalized bladder epithelial cells SV-HUC-1, the expression of miR-5194 in bladder cancer cells was significantly down-regulated ( P<0.01). After 5-Aza-CdR treatment, the expression of miR-5194 in bladder cancer cells was significantly increased ( P<0.01). The number of colonies in miR-5194 group and NC group were 31.30 ± 8.09 and 99.98 ± 10.53, respectively, and the proliferation ability of UMUC3 cells in miR-5194 group was weakened ( P<0.01). The migration rates of UMUC3 cells in miR-5194 group and NC group were (31.50 ± 7.17)% and (76.06 ± 4.86)%, respectively, and the migration ability of UMUC3 cells in miR-5194 group was weakened ( P<0.01). miR-5194 can target bind PAK2 gene ( P<0.01). The relative expression of PAK2 mRNA in UMUC3 cells of miR-5194 group and NC group were 1.02 ± 0.34 and 5.43 ± 0.76, respectively, and miR-5194 could negatively regulate the expression of PAK2 mRNA ( P<0.01). Compared with the NC group, the expression of PAK2 protein, the expression of proliferation-related proteins CDK1 and Cyclin B, and the expression of migration-related proteins FOXC2 and E47 were down-regulated in UMUC3 cells with miR-5194 overexpression. Conclusion:The methylation level of miR-5194 promoter in bladder cancer tissue was significantly increased, and miR-5194 inhibited the proliferation and migration of bladder cancer cells by targeting down-regulation of PAK2 expression in bladder cancer UMUC3 cells.
10.The role of SIRT7 in regulating epithelial-mesenchymal transition(EMT)to promote glioma cell proliferation and migration
Jiang-Ting WANG ; Kai SUN ; Mou GAO ; Gang CHENG ; Wen-Ying LYU ; Chun-Hui ZHOU ; Lei LIANG ; Jian-Ning ZHANG
Medical Journal of Chinese People's Liberation Army 2025;50(1):57-68
Objective To investigate the expression of the histone deacetylase SIRT7 in glioma cells and its impact on epithelial-mesenchymal transformation(EMT),as well as its effects on proliferative,migratory and invasive capabilities of glioma cells.Methods Bioinformatics analysis was conducted on data from glioma patients in the Cancer Genome Atlas(TCGA)and the Chinese glioma Genome Atlas(CGGA)databases to explore the expression of SIRT7 gene in gliomas and its correlation with tumor grading,molecular characteristics and patient clinical prognosis.Glioma cells were randomly divided into control,SIRT7 knockdown,SIRT7 overexpression,drug treatment(10 μmol/L hydrochlorothiazide)and drug(10 μmol/L hydrochlorothiazide)+SIRT7 overexpression groups.The CCK-8 assay,cell scratch assay and Transwell assay were used to observe the effects of upregulating and downregulating SIRT7 expression on glioma cell proliferation,migration and invasion.RT-qPCR and Western blotting were employed to detect the effects of SIRT7 on the expression of neural cadherin(N-cadherin),Vimentin,E-cadherin,transforming growth factor-β(TGF-β),Ki-67,and Smad3 protein in glioma cells.Nude mouse tumor-bearing experiments were conducted to observe the effect of SIRT7 knockdown on glioma growth.Results Higher expression levels of SIRT7 gene were associated with poorer clinical prognosis(P<0.0001).SIRT7 expression levels were significantly correlated with tumor grading and 1p19q coding status(P<0.01).Compared with normal HA cells,glioma cells showed significantly increased SIRT7 expression levels(P<0.01).CCK-8 assay results indicated that,compared with control group,the proliferation activity of glioma cells in SIRT7 knockout group was significantly decreased(P<0.01),while SIRT7 overexpression group showed significantly increased proliferation activity(P<0.01).EdU assay results showed that,compared with control group,the proportion of glioma cells in the proliferative stage was significantly decreased in SIRT7 knockdown group(P<0.01),and significantly increased in SIRT7 overexpression group(P<0.01).Western blotting results revealed that,compared with control group,the protein expression levels of TGF-β,Smad3,N-cadherin and Vimentin were significantly decreased in SIRT7 knockdown group(P<0.01),while the expression level of E-cadherin protein was significantly increased(P<0.05).SIRT7 overexpression group showed significantly increased protein expression levels of TGF-β,Smad3,N-cadherin and Vimentin(P<0.05),and a significantly decrease in E-cadherin protein expression level(P<0.05).Scratch assay results indicated that,compared with control group,the migration ability of cells in SIRT7 knockdown group and drug group was significantly decreased(P<0.01),and SIRT7 overexpression group showed significantly increased cell migration ability(P<0.05).Compared with drug group,drug+SIRT7 overexpression group exhibited significantly increased cell migration ability(P<0.01).Transwell assay results showed that,compared with control group,the migration and invasion abilities of cells in SIRT7 knockdown group and drug group were significantly decreased(P<0.01),and SIRT7 overexpression group exhibited significantly increased migration and invasion abilities(P<0.01).Compared with drug group,drug+SIRT7 overexpression group showed significantly increased migration and invasion abilities(P<0.01).Nude mouse tumor-bearing assay results indicated that the volume and weight of glioma in SIRT7 knockdown group were significantly reduced compared with control group(P<0.01).Conclusions Glioma patients with high SIRT7 expression have poorer clinical prognosis.SIRT7 can regulate the TGF-β/Smad3 pathway to mediate EMT,promoting the proliferation and migration of glioma cells.SIRT7 knockdown can inhibit the growth of transplanted gliomas in nude mice.


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