1.Research progress in the mechanism of stimulator of interferon genes in type 2 diabetes mellitus and its microvascular complication
Min LI ; Xiaoyan QI ; Zhenyu YANG ; Weiran YE ; Yanbo LI
Chinese Journal of Diabetes 2024;32(3):227-230
Type 2 diabetes mellitus(T2DM)is a chronic metabolic disease that can lead to the damage of multiple tissues and organs throughout the body.Stimulator of interferon genes(STING)is an endoplasmic reticulum membrane protein that acts as an indirect cytoplasmic DNA sensor.The activation of the STING signaling pathway may be involved in T2DM and its microvascular complications through various mechanisms.This article reviews the research progress in the mechanism of STING in T2DM and its microvascular complications.
2.Laboratory malaria re-examination and evaluation of malaria diagnostic capability in Shanghai Municipal Malaria Diagnostic Reference Laboratory from 2017 to 2022
Yaoguang ZHANG ; Zhenyu WANG ; Min ZHU ; Li JIANG ; Qian ZHU ; Xiaojiang MA ; Qing YU ; Jian CHEN
Chinese Journal of Schistosomiasis Control 2024;36(5):521-526
Objective To evaluate the malaria diagnostic capability in Shanghai Municipal Malaria Diagnostic Reference Laboratory from 2017 to 2022 and to analyze factors affecting the diagnosis results, so as to provide the scientific evidence for increasing the laboratory malaria diagnostic capability during the post-elimination stage. Methods Plasmodium-negative blood smears were randomly sampled using a proportional sampling method each quarter during the period from 2017 to 2022 and scored by Shanghai Municipal Malaria Diagnostic Reference Laboratory. Malaria cases’ blood samples from district centers for disease control and prevention in Shanghai Municipality were re-reviewed using microscopy and multiplex PCR assay to evaluate the capability of malaria diagnosis. Results A total of 7 746 quality control blood smears were collected from district centers for disease control and prevention in Shanghai Municipality from 2017 to 2022, with a mean score of (76.74 ± 14.34) points and a qualification rate of 86.65% (6 712/7 746). A total of 387 blood smears were re-reviewed from 2017 to 2022, with an overall coincidence of 96.38% (373/387) for malaria diagnosis and 95.06% (308/324) for parasite species identification, and there were no significant differences in the coincidence for either malaria diagnosis (χ2 = 2.57, P > 0.05) or parasite species identification among years (χ2 = 1.04, P > 0.05). A total of 384 whole blood samples were collected from district centers for disease control and prevention, and the detection of whole blood samples was 70.31% (270/384) in district centers for disease control and prevention. All 384 whole blood samples were re-reviewed by Shanghai Municipal Malaria Diagnostic Reference Laboratory using a multiplex PCR assay from 2017 to 2022, with an overall coincidence of 94.07% (254/270) for malaria diagnosis and 99.55% (223/224) for parasite species identification, and there were no significant differences in the coincidence for either malaria diagnosis (χ2 = 5.77, P > 0.05) or parasite species identification among years (χ2 = 8.37, P > 0.05). The overall coincidence rates of Plasmodium-positive and negative whole blood samples were 100.00% (224/224) and 65.22% (30/46) in district centers for disease control and prevention, with a significant difference (χ2 = 82.82, P < 0.001), and there was a significant difference in the coincidence rate for identification of P. falciparum, P. vivax, P. malariae and P. ovale (χ2 = 24.28, P < 0.001). A total of 1 584 blind blood smears subjected to microscopic examinations by centers for disease control and prevention and medical institutions across all districts in Shanghai Municipality from 2017 to 2022, with a 96.15% (1 523/1 584) correct rate for malaria diagnosis and 85.07% (1 003/1 179) for parasite species identification, and there were significant differences in the correct rate of both malaria diagnosis (χ2 = 20.98, P < 0.001) and parasite species identification among years (χ2 = 70.77, P < 0.001). A total of 320 blind nucleic acid samples from malaria cases were tested, with a 99.38% (318/320) correct rate for malaria diagnosis and 100.00% (225/225) for parasite species identification, and there was no significant difference in the correct rate of malaria diagnosis among years (χ2 = 6.04, P > 0.05). Conclusions There were still shortcomings in blood smears preparation, microscopic examinations and nucleic acid testing in centers for disease control and prevention across all districts in Shanghai Municipality from 2017 to 2022. A greater role in the quality control of malaria diagnosis is recommended for Shanghai Municipal Malaria Diagnostic Reference Laboratory to prevent the re-establishment of imported malaria and consolidate the elimination achievements.
4.Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis
Shanghao LIU ; Hongmei ZU ; Yan HUANG ; Xiaoqing GUO ; Huiling XIANG ; Tong DANG ; Xiaoyan LI ; Zhaolan YAN ; Yajing LI ; Fei LIU ; Jia SUN ; Ruixin SONG ; Junqing YAN ; Qing YE ; Jing WANG ; Xianmei MENG ; Haiying WANG ; Zhenyu JIANG ; Lei HUANG ; Fanping MENG ; Guo ZHANG ; Wenjuan WANG ; Shaoqi YANG ; Shengjuan HU ; Jigang RUAN ; Chuang LEI ; Qinghai WANG ; Hongling TIAN ; Qi ZHENG ; Yiling LI ; Ningning WANG ; Huipeng CUI ; Yanmeng WANG ; Zhangshu QU ; Min YUAN ; Yijun LIU ; Ying CHEN ; Yuxiang XIA ; Yayuan LIU ; Ying LIU ; Suxuan QU ; Hong TAO ; Ruichun SHI ; Xiaoting YANG ; Dan JIN ; Dan SU ; Yongfeng YANG ; Wei YE ; Na LIU ; Rongyu TANG ; Quan ZHANG ; Qin LIU ; Gaoliang ZOU ; Ziyue LI ; Caiyan ZHAO ; Qian ZHAO ; Qingge ZHANG ; Huafang GAO ; Tao MENG ; Jie LI ; Weihua WU ; Jian WANG ; Chuanlong YANG ; Hui LYU ; Chuan LIU ; Fusheng WANG ; Junliang FU ; Xiaolong QI
Chinese Journal of Laboratory Medicine 2023;46(1):52-61
Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.
5.Effects of microRNA-106b on migration and invasion of human malignant pleural mesothelioma cell NCI-H2452
Yanan GAO ; Min ZHANG ; Fangfang ZHANG ; Zhenyu JIA ; Xiuyuan YUAN ; Lijin ZHU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(9):648-654
Objective:To investigate the inhibitory effect of microRNA-106b in the process of migration and invasion of human malignant pleural mesothelioma cell NCI-H2452.Methods:In April 2017, the expression level of miRNA-106b in malignant pleural mesothelioma cells (NCI-H2452, MSTO-211H, NCI-H2052) and normal mesothelial cells MeT-5A was detected and analyzed. Using NCI-H2452 cells as a model, the NCI-H2452 cell model with miRNA-106b overexpression was established by transfecting miRNA-106b mimics. The expression level of miRNA-106b in the cells was detected by real-time fluorescent quantitative PCR. The effect of miRNA-106b on the migration and invasion ability of NCI-H2452 cells was analyzed. The gene expression data of malignant mesothelioma and the downstream target gene data of miRNA-106b in public databases were analyzed to screen the downstream target genes of miRNA-106b in mesothelioma cells that affect cell migration and invasion ability, and to verify the expression of this gene in NCI-H2452 cells with miRNA-106b overexpression.Results:The expression of miRNA-106b in three MPM cells was decreased compared with MeT-5A cells ( P<0.001) . The expression level of miRNA-106b was significantly increased after transfection of miRNA-106b mimics ( P<0.001) . The scratch migration levels of the experimental group were 28.45%±4.37%, 38.12%±4.82% and 50.06%±8.92% at 24h, 31h and 48h, respectively. Compared with the control group, the migration level decreased by 37.48%±2.65%, 49.21%±3.45% and 68.14%±3.81% ( P<0.01) . The number of cell migration and invasion decreased in the experimental group compared with the control group ( P<0.001) . Public databases were used to screen and analyze the possibility that TCF21 gene, as a downstream target gene, could affect the migration and invasion ability of MPM cells. The expression level of TCF21 gene was increased after transfection of miRNA-106b mimics in NCI-H2452 cells ( P=0.009) . Conclusion:MiRNA-106b can inhibit the migration and invasion of NCI-H2452 cells and increase the expression of TCF21 gene.
6.Effects of microRNA-106b on migration and invasion of human malignant pleural mesothelioma cell NCI-H2452
Yanan GAO ; Min ZHANG ; Fangfang ZHANG ; Zhenyu JIA ; Xiuyuan YUAN ; Lijin ZHU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(9):648-654
Objective:To investigate the inhibitory effect of microRNA-106b in the process of migration and invasion of human malignant pleural mesothelioma cell NCI-H2452.Methods:In April 2017, the expression level of miRNA-106b in malignant pleural mesothelioma cells (NCI-H2452, MSTO-211H, NCI-H2052) and normal mesothelial cells MeT-5A was detected and analyzed. Using NCI-H2452 cells as a model, the NCI-H2452 cell model with miRNA-106b overexpression was established by transfecting miRNA-106b mimics. The expression level of miRNA-106b in the cells was detected by real-time fluorescent quantitative PCR. The effect of miRNA-106b on the migration and invasion ability of NCI-H2452 cells was analyzed. The gene expression data of malignant mesothelioma and the downstream target gene data of miRNA-106b in public databases were analyzed to screen the downstream target genes of miRNA-106b in mesothelioma cells that affect cell migration and invasion ability, and to verify the expression of this gene in NCI-H2452 cells with miRNA-106b overexpression.Results:The expression of miRNA-106b in three MPM cells was decreased compared with MeT-5A cells ( P<0.001) . The expression level of miRNA-106b was significantly increased after transfection of miRNA-106b mimics ( P<0.001) . The scratch migration levels of the experimental group were 28.45%±4.37%, 38.12%±4.82% and 50.06%±8.92% at 24h, 31h and 48h, respectively. Compared with the control group, the migration level decreased by 37.48%±2.65%, 49.21%±3.45% and 68.14%±3.81% ( P<0.01) . The number of cell migration and invasion decreased in the experimental group compared with the control group ( P<0.001) . Public databases were used to screen and analyze the possibility that TCF21 gene, as a downstream target gene, could affect the migration and invasion ability of MPM cells. The expression level of TCF21 gene was increased after transfection of miRNA-106b mimics in NCI-H2452 cells ( P=0.009) . Conclusion:MiRNA-106b can inhibit the migration and invasion of NCI-H2452 cells and increase the expression of TCF21 gene.
7.Impact of different diagnostic criteria for assessing mild micro-hepatic encephalopathy in liver cirrhosis: an analysis based on a prospective, multicenter, real-world study
Xiaoyan LI ; Shanghao LIU ; Chuan LIU ; Hongmei ZU ; Xiaoqing GUO ; Huiling XIANG ; Yan HUANG ; Zhaolan YAN ; Yajing LI ; Jia SUN ; Ruixin SONG ; Junqing YAN ; Qing YE ; Fei LIU ; Lei HUANG ; Fanping MENG ; Xiaoning ZHANG ; Shaoqi YANG ; Shengjuan HU ; Jigang RUAN ; Yiling LI ; Ningning WANG ; Huipeng CUI ; Yanmeng WANG ; Chuang LEI ; Qinghai WANG ; Hongling TIAN ; Zhangshu QU ; Min YUAN ; Ruichun SHI ; Xiaoting YANG ; Dan JIN ; Dan SU ; Yijun LIU ; Ying CHEN ; Yuxiang XIA ; Yongzhong LI ; Qiaohua YANG ; Huai LI ; Xuelan ZHAO ; Zemin TIAN ; Hongji YU ; Xiaojuan ZHANG ; Chenxi WU ; Zhijian WU ; Shengqiang LI ; Qian SHEN ; Xuemei LIU ; Jianping HU ; Manqun WU ; Tong DANG ; Jing WANG ; Xianmei MENG ; Haiying WANG ; Zhenyu JIANG ; Yayuan LIU ; Ying LIU ; Suxuan QU ; Hong TAO ; Dongmei YAN ; Jun LIU ; Wei FU ; Jie YU ; Fusheng WANG ; Xiaolong QI ; Junliang FU
Chinese Journal of Hepatology 2023;31(9):961-968
Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.
8.Sex differences in systemic lupus erythematosus (SLE): an inception cohort of the Chinese SLE Treatment and Research Group (CSTAR) registry XVII.
Yinli GUI ; Wei BAI ; Jian XU ; Xinwang DUAN ; Feng ZHAN ; Chen ZHAO ; Zhenyu JIANG ; Zhijun LI ; Lijun WU ; Shengyun LIU ; Min YANG ; Wei WEI ; Ziqian WANG ; Jiuliang ZHAO ; Qian WANG ; Xiaomei LENG ; Xinping TIAN ; Mengtao LI ; Yan ZHAO ; Xiaofeng ZENG
Chinese Medical Journal 2022;135(18):2191-2199
BACKGROUND:
The onset and clinical presentation of systemic lupus erythematosus (SLE) are sex-related. Few studies have investigated the distinctions in clinical characteristics and treatment preferences in male and female SLE patients in the initial cohort. This study aimed to improve the understanding of Chinese SLE patients by characterizing the different sexes of SLE patients in the inception cohort.
METHODS:
Based on the initial patient cohort established by the Chinese SLE Treatment and Research Group, a total of 8713 patients (795 men and 7918 women) with newly diagnosed SLE were enrolled between April 2009 and March 2021. Of these, 2900 patients (347 men and 2553 women) were eligible for lupus nephritis (LN). A cross-sectional analysis of the baseline demographic characteristics, clinical manifestations, laboratory parameters, organ damage, initial treatment regimens, and renal pathology classification was performed according to sex.
RESULTS:
In the SLE group, as compared to female patients, male patients had a later age of onset (male vs. female: 37.0 ± 15.8 years vs. 35.1 ± 13.7 years, P = 0.006) and a higher SLE International Collaborative Clinic/American College of Rheumatology damage index score (male vs. female: 0.47 ± 1.13 vs. 0.34 ± 0.81, P = 0.015), LN (male vs. female: 43.6% vs. 32.2%, P < 0.001), fever (male vs. female: 18.0% vs. 14.6%, P = 0.010), thrombocytopenia (male vs. female: 21.4% vs. 18.5%, P = 0.050), serositis (male vs. female: 14.7% vs. 11.7%, P = 0.013), renal damage (male vs. female: 11.1% vs. 7.4%, P < 0.001), and treatment with cyclophosphamide (CYC) (P < 0.001). The frequency of leukopenia (male vs. female: 20.5% vs. 25.4%, P = 0.002) and arthritis (male vs. female: 22.0% vs. 29.9%, P < 0.001) was less in male patients with SLE. In LN, no differences were observed in disease duration, SLE Disease Activity Index score, renal biopsy pathological typing, or 24-h urine protein quantification among the sexes. In comparisons with female patients with LN, male patients had later onset ages (P = 0.026), high serum creatinine (P < 0.001), higher end-stage renal failure rates (P = 0.002), musculoskeletal damage (P = 0.023), cardiovascular impairment (P = 0.009), and CYC use (P = 0.001); while leukopenia (P = 0.017), arthritis (P = 0.014), and mycophenolate usage (P = 0.013) rates were lower.
CONCLUSIONS
Male SLE patients had more severe organ damage and a higher LN incidence compared with female SLE patients; therefore, they may require more aggressive initial treatment compared to female patients.
Humans
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Female
;
Male
;
Cross-Sectional Studies
;
Sex Characteristics
;
East Asian People
;
Severity of Illness Index
;
Lupus Erythematosus, Systemic/diagnosis*
;
Lupus Nephritis/pathology*
;
Registries
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Cyclophosphamide/therapeutic use*
;
Thrombocytopenia
;
Leukopenia/drug therapy*
;
Arthritis
9.Early and intermediate outcomes of second-grade false-lumen endovascular occlusive repair for aortic dissection
Min ZHOU ; Zhenyu SHI ; Lixin WANG ; Daqiao GUO ; Xin XU ; Bin CHEN ; Junhao JIANG ; Jue YANG ; Weiguo FU
Chinese Journal of General Surgery 2021;36(1):5-9
Objective:To summarize the early and intermediate outcomes of second-grade false-lumen endovascular occlusive repair (FLEVOR) for aortic dissection.Methods:The clinical data of 12 patients undergoing second-grade FLEVOR after proximal repair of aortic dissection at our center from Aug 2016 to Aug 2019 was retrospectively analyzed.Results:The mean age was (51.3±14.9) years old. Four patients received open repair due to Stanford type A aortic dissection previously, the other 8 patients underwent thoracic endovascular aortic repair for Stanford type B aortic dissection. The time to the proximal repair varied from 3 months to 16 years. The technical success rate was 100%. Visceral ischemia, early spinal cord ischemia and in-hospital death did not occur perioperatively. The mean follow-up time was 16.7 months. Persistent false lumen perfusion was found in 3 patients, complete thrombosis of false lumen was achieved in the other 8 patients. The maximum diameter of abdominal aorta decreased in 8 (72.7%) patients.Conclusions:FLEVOR could block the blood flow from the false lumen and induce the thrombosis of false lumen, which promotes the aortic remodeling. Meanwhile, FLEVOR could protect the blood supply of spinal cord and viscera, and reduce the risk of type Ⅱ endoleaks.
10.Risk factors for postoperative central nervous system infection
Xilan TAN ; Qianru XIANG ; Min AN ; Zhenyu ZHUANG ; Xuejiao WANG ; Xiaozhu ZHONG
Chinese Journal of Neuromedicine 2021;20(7):705-710
Objective:To clarify the risk factors for post-operative central nervous system infection (PCNSI) to provide references for prevention and treatment of PCNSI.Methods:A total of 397 patients with neurosurgery diseases, admitted to and accepted 403 surgeries in our hospital from February 1 st, 2015 to December 30 th, 2015, were chosen in our study; their clinical data were collected. The incidence of PCNSI was analyzed. Risk factors for PCNSI were analyzed by univariate analysis and multivariate Logistic regression analysis. The ajusted specific infection rate of PCNSI was calculated in 12 chief surgeons who performed≥8 operations during the study period to assess the influence of surgeons in PCNSI incidence. Results:The PCNSI incidence in these 397 patients was 9.2% (37/403). The cerebrospinal fluid (CSF) culture positive rate was 29.7% (11/37), including 6 (54.6%) with positive gram staining. Univariate analysis showed that as compared with the non-infected group (366 surgeries), patients in the PCSNI group (37 surgeries) had significantly higher National Nosocomial Infections Surveillance (NNIS) scale, significantly higher proportion of patients with preoperative stay>6 d, significantly longer operative duration, and statistically higher proportion of involvement of scrub nurses with experience in fewer than 8 procedures ( P<0.05). Multivariate Logistic regression analysis showed operative duration ( OR=1.389, 95%CI: 1.202-1.606, P=0.000) and involvement of scrub nurses with experience in fewer than 8 procedures ( OR=2.860, 95%CI: 1.276-6.412, P=0.011) were independent risk factors for PCNSI. After adjustment by NNIS scale, the ajusted specific infection rate of PCNSI in 12 chief surgeons was 20.0%, 23.0%, 17.3%, 18.2%, 13.4%, 12.5%, 6.3%, 8.0%, 5.2%, 4.0%, 0.0%, and 0.0%, respectively, enjoying obvious differences. Conclusion:Specialized infection control training should give to surgeons with high adjusted specific infection rate of PCNSI; this training, shortening operative duration, and training of neurosurgery specialist nurses will be important measures to reduce PCNSI incidence.

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