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Table of Content

10 June 2023, Volume 39 Issue 11
Coronavirus(COVID-19)
Practical procedure of invasive mechanical ventilation in adult critical coronavirus disease 2019 patients 
HE Zhijie, LI Fangyi, ZHOU Lixin, TANG Zhanhong, QIAN Kejian, KOU Qiuye, TANG Jiewen, WANG Tin⁃ ghuai.
2023, 39(11):  1325-1330.  doi:10.3969/j.issn.1006⁃5725.2023.11.001
Abstract ( 265 )  
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Timely and appropriate invasive mechanical ventilation is one of the important treatment meth⁃ ods for critical COVID ⁃19 patients recommended by the current guidelines. However,how to accurately evaluate and effectively treat critically ill patients with invasive mechanical ventilation is very important for reducing the heterogeneity of treatment and improving the prognosis of COVID⁃19 patients with invasive mechanical ventilation in different regions,especially in primary hospitals. Based on the recommendations from previous clinical practice guidelines,the National Health Technology Promotion and Application Service Platform of China Medical and Health Development Foundation made this practical procedure of invasive mechanical ventilation in adult critical COVID⁃19 patients,in order to promote the standard application of invasive mechanical ventilation in the treatment of adult critical COVID⁃19 patients. 【Key words】 critical; coronavirus disease 2019; invasive mechanical ventilation; practical procedure
Review
Upgrade the TB control and prevention strategy,optimize the TB cases detection 
WANG Shengfen, ZHAO Yanlin.
2023, 39(11):  1331-1334.  doi:10.3969/j.issn.1006⁃5725.2023.11.002
Abstract ( 210 )   PDF (1246KB) ( 110 )  
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The current case finding strategies cannot identify all tuberculosis patients,and the undetected tuberculosis patients continue to spread the disease. It is important to integrate of new and the current strategies to improve case finding strategies,which is of great significance for reducing the burden of tuberculosis in China. 
Suggestions on accelerating screening and preventive treatment of latent tuberculosis infection in China 
MA Yan, CHENG Shiming.
2023, 39(11):  1335-1341.  doi:10.3969/j.issn.1006⁃5725.2023.11.003
Abstract ( 201 )   PDF (1372KB) ( 102 )  
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Screening for latent tuberculosis infection (LTBI)in high ⁃ risk populations and providing preventive treatment for LTBI are important tools to reduce morbidity and achieve the global strategy to stop TB. At present,the burden of LTBI and its epidemic characteristics as well as the status quo of preventive treatment are still unclear. Relevant studies are still in the exploratory stage,and no mature intervention strategies have been formed yet. The present status,existing problems and suggestions of screening and preventive treatment of LTBI were systematically expounded,so as to provide a basis for the formulation of prevention and treatment strategies of LTBI and preventive treatment. 
Demands,problems and coping strategies to medical laboratory test for clinical diagnosis,treatment, prevention and control of tuberculosis
LIU Zhihui, LIU Jianxiong.
2023, 39(11):  1342-1346.  doi:10.3969/j.issn.1006⁃5725.2023.11.004
Abstract ( 172 )   PDF (1392KB) ( 107 )  
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Modern medical clinical decision ⁃ making are increasingly dependent on medical laboratory, which holds true for tuberculosis. However,so far the data of clinical practice have demonstrated that pathogenic evidences have not been obtained for more than 40% of tuberculosis cases from clinical laboratory. And delays occurring in the process of diagnosis and treatment are also general.Accurate and rapid laboratory techniques and methods have always been eagerly anticipated. This review tries to discuss the needs and problems to medical lab⁃ oratory for clinical diagnosis,precision medicine,prevention and control of tuberculosis.Our some simple cognition on how to get human out of the trouble are briefly given. 
Special topic written talk
Correlation between drug resistance of Mycobacterium avium and Mycobacterium intracellulare and clinical prognosis in Guangzhou
HE Xiangrong, ZHANG Tianyu, WANG Xinyu, LIU Zhihui, WANG Qi, SU Ning, HU Jinxing.
2023, 39(11):  1347-1352.  doi:10.3969/j.issn.1006⁃5725.2023.11.005
Abstract ( 218 )   PDF (1120KB) ( 102 )  
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Objective To clarify the relationship between different species of Mycobacterium avium complex(MAC),drug sensitivity and clinical prognosis in Guangzhou. Methods The clinical isolates of MAC from 2018 to 2020 were collected from the Mycobacterium Strain Bank in Guangzhou,and the MAC strains of MAC lung disease patients were sequenced to identify them by 16S rRNA,ITS,rpoB,hsp65 multi⁃target gene sequencing. MIC50 and MIC90 of its minimum inhibitory concentration(MIC)were determined by microplate method to deter⁃ mine its drug sensitivity. The success of clinical treatment can be judged according to the clinical symptoms,DR/ CT radiology and pathogen culture results. Results (1)There were 67 strains of Mycobacterium intracellulare (73.63%)and 21 strains of Mycobacterium avium(23.08%)in 91 clinical isolates of MAC.(2)The resistance rates of Mycobacterium avium and Mycobacterium intracellular to amikacin and ethambutol were different(P < 0.05).(3)There was significant difference in the treatment success rate between M.aviumpulmonary disease and M.intracellularepulmonary disease(66.67% vs. 41.27%,χ2 = 6.053,P < 0.05). Conclusion M.intracellulare and M.avium were the main clinical isolates of MAC in Guangzhou,and there were differences in drug resistance and clinical prognosis among different MAC species. For patients with NTM pulmonary disease,strain identification and in vitro drug susceptibility tests should be conducted,and clinical treatment protocols should be formulated and optimized based on the above results. 
Analysis on correlation between isoniazid ⁃ resistant gene mutations in Mycobacterium tuberculosis and resistance to other anti⁃tuberculosis drugs 
GONG Lan, NIU Qun, WANG Nan, LEI Jie, WU Ling, DENG Li, XIE Bei, WANG Qi, LI Hua, YANG Yu, LIU Zhihui, MENG Fanrong.
2023, 39(11):  1353-1358.  doi:10.3969/j.issn.1006⁃5725.2023.11.006
Abstract ( 226 )   PDF (1131KB) ( 362 )  
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Objective To study the effects of resistance to other anti ⁃tuberculosis drugs on mutations of isoniazid resistance related genes in M.tuberculosis for further accurately understanding the molecular mechanism of isoniazid resistance in M.tuberculosis. Methods The M.tuberculosis isolates which have complete drug sensitivity test(DST)data of eleven kinds of anti⁃tuberculosis drugs(isoniazid,rifampicin,ethambutol,streptomycin,amika⁃ cin,clarithromycin,levofloxacin,moxifloxacin,rifambdin,propylthioisonicotinamide and p⁃aminosalicylic acid) were were sampled from the bio⁃bank of Mycobacteria in Guangzhou. Then their katG,mabA⁃inhA,oxyR⁃ahpC, kasA and ndh genes were sequenced,and gene mutations were analyzed by comparing with the sequences of these genes of M.tuberculosis reference strain H37Rv.Statistical comparative analysis of the total gene mutation frequen⁃ cies of five genes between bacterial florae of H(- R/F/O)- and H(- R/F/O)+ ,H+ R- and H+ R+ ,H+ F- and H+ F+ ,and H+ O- and H+ O+ resistant phenotypes were performed by using Chi⁃square test(Among them,“R”,“H”,“F”,“O”, “+”and“-”represent rifampicin,isoniazid,Levofloxacin or moxifloxacin and seven kinds of other drugs,drug⁃ resistance and drug⁃susceptibility respectively. Results The first,the total gene mutation frequency of five genes in M.tuberculosis strains with H- (R/F/O)- was 11.32%(12/106)while the frequency was 40.54%(15/37)in M.tuberculosis strains with H- (R/F/O)+ among 143 isoniazid ⁃sensitive mycobacterium tuberculosis strains,which there was significant differences between them(χ2 = 15.289,P ˂ 0.001). The second,the total gene mutation frequency of five genes in M.tuberculosis strains with H+ R- ,H+ R+ ,H+ F- ,H+ F+ ,H+ O- and H+ O+ were 47.87%(45/ 94),93.85%(122/130),68.64%(116/169),89.09%(49/55),55.56%(15/27)and 77.16%(152/197). There were significant differences between M.tuberculosis strains with H+ R- and H+ R+ ,H+ F- and H+ F+ ,H+ O- and H+ O+ based on their chi⁃square values of 60.778,11.99 and 5.841 and P values of ˂ 0.001,0.001 and 0.016, respectively. Conclusions It is essential that important effects on isoniazid resistance related genes mutations in M.tuberculosis from other anti ⁃ tuberculosis drugs resistance should be studied extensively and deeply although these mutations were usually decided by their sensitivity to isoniazid. 
Drug resistance of Mycobacterium tuberculosis co⁃occurring with diabetes and tuberculosis 
YANG Zilong, YUAN Yuan, WANG Min, CHEN Yumei, FENG Zhiyu, WU Di, ZHANG Hong, CHEN Zeying, HUANG Xian⁃ lin, KUANG Haobin.
2023, 39(11):  1359-1363.  doi:10.3969/j.issn.1006⁃5725.2023.11.007
Abstract ( 183 )   PDF (1118KB) ( 158 )  
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Objective To investigate the drug resistance of Mycobacterium tuberculosis in diabetes melli⁃ tus and pulmonary tuberculosis comorbidity(DM⁃TB). Methods A retrospective case⁃control study was conducted to review and analyze the clinical data of 1948 patients who was diagnosed with DM⁃TB in the inpatient and outpa⁃ tient departments of Guangzhou Chest Hospital from January 2018 to December 2020. A total of 1012 cases with positive Mycobacterium tuberculosis culture and drug susceptibility results were screened out. After excluding the cases with incomplete data,438 cases with complete data were included for analyses of age,gender,haemoglo⁃ bin,albumin,glycatedhaemoglobin(HbA1c),extent of lesions,number of cavities,treatment history,sputum bacterial load and rifampicin resistance. The description method and Pearson Chi ⁃ square test(χ2 )were used to compare analyze the first and second line drug resistance of the strains from the 1012 patients. Among the selected cases,?86 patients who were resistant against rifampicin were assigned as rifampicin⁃resistant(RR⁃TB)group, and then another 86 patients were randomly selected from the rest 352 patients sensitive to rifampicin by random digit table method as rifampicin ⁃sensitive(RS ⁃TB)group.The methods of?t ⁃test,rank ⁃sum test or Pearson Chi square test(χ2 )were used for the analyses. The clinical characteristics of the included cases were taken as inde⁃ pendent variables and rifampicin resistance as dependent variables. Multivariate logistic regression analysis was per⁃ formed to screen out independent risk factors for RR ⁃TB in DM ⁃TB patients. Results Among the 1012 patients with TB⁃DM,the rate of rifampicin resistance was 13.3%,the rate of initial rifampicin resistance was 6.8%,the rate of retreatment rifampicin resistance was 45.9%,with significant differences(χ2 = 127.956,P = 0.000). The rate of multidrug⁃resistance was 11.77%,the rate of initial multidrug⁃resistance was 5.5%,the rate of retreatment multidrug ⁃ resistance was 42.9%,with significant difference between the two groups(χ2 = 191.468,P = 0.000). Multivariate logistic regression analysis showed that retreatment(OR = 9.517,95%CI:4.333 ~ 20.904,P = 0.000) was an independent risk factor for rifampicin resistance in the DM⁃TB patients,and senior ages(OR = 0.440,95%CI: 0.252 ~ 0.771,P = 0.004)was an independent protective factor. Conclusion The prevalence of rifampicin resis⁃ tance in DM⁃TB isrelatively high,especially among young patients and retreated patients. For DM⁃TB population, timely drug sensitivity test can help the early diagnosis and treatment of rifampicin⁃resistant tuberculosis. 
Analysis of Diagnosis delay of Patients with pulmonary tuberculosis in Yingde City,Guangdong from 2010 to 2020 
ZHUO Wenji, ZHANG Jianhui, LUO Jilun, LIAO Qinghua, YU Meiling, YANG Weiling, CHEN Wen⁃ han, ZHONG Nairong, ZHONG Yuexiang.
2023, 39(11):  1364-1368.  doi:10.3969/j.issn.1006⁃5725.2023.11.008
Abstract ( 165 )   PDF (1149KB) ( 58 )  
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Objective To analize the influencing factors of diagnosis delay of patients with pulmonary tuberculosis in this area,and further to provide a scientific basis for improving continuously regional tuberculosis control plans and measures. Methods The reported information of new pulmonary tuberculosis cases in Yingde City,Guangdong from 2010⁃2020 was collected and abstracted from Tuberculosis Information Management System of China Information System for Disease Control and Prevention. Furthermore,the general levels trend and influencing factors(including gender,age,residence,medical institution of providing diagnosis,etc)of diagnosis delay, which defined as more than 28 days from the date of symptom onset to the date of diagnosis,were retrospectively analyzed during eleven years. Results (1)The total number of new pulmonary tuberculosis cases registered was 11 973 cases,and diagnosis delay occurred in 3 189 cases(accounting for 26.63%). And the median time of diagnosis delay was 17 days,which this time was calculated from the 29th day of symptom start date to the clear diagnosis date.(2)The ratio of diagnosis delay were about 30% in 2010,2011 and 2020 and that of the other years were fluctuating between 22.35% ~ 26.65%. The trend of median time of diagnosis delay was increased year by year in 2010⁃2014 and median time of diagnosis delay jumped to a peak of 33 days in 2014. Fortunately,the trend in subsequent 6 years was a general decline and the minimum of median time of diagnosis delay was 9 days in 2018.(3)The ratio of diagnosis delay in ≥ 60 years group was 22.61% and significantly lower than other ages groups (P = 0.000). The ratio of diagnosis delay of cases living in district,suburban,rural increased in turn and presented significant difference(P = 0.000)among them. But,there was no significant difference between male and female (P = 0.462).(4)The median time of diagnosis delay were 17 days and 16 days for male and female and 10,13, 18 and 20 days for cases of < 18,18 ~ 44,45 ~ 59 and ≥ 60 age groups respectively. It were 19,17,16 days for cases from suburbs,rural and urban and 20,15,12 and 8 days for cases visiting to comprehensive medical institu⁃ tions,town health center and prison hospitals,chronic disease prevention hospitals respectively. Conclusion The overall situation of diagnosis delay for pulmonary tuberculosis have obtained continuous improvement in Yingde City,Guangdong. However its major influencing factors,including age,residence,medical institution,etc,must be payed more attention and suitable new strategies and measures must be formulated and fulfilled.
Spatial ⁃ temporal sequence and molecular epidemiology analysis on a tuberculosis cluster in a high school 
CHEN Ruiming, LIN Jianxiong, CHEN Zhuanghao, LIU Suyang, FU Hui.
2023, 39(11):  1369-1375.  doi:10.3969/j.issn.1006⁃5725.2023.11.009
Abstract ( 175 )   PDF (1448KB) ( 91 )  
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Objective To investigate clearly the causes,characteristics and patterns of the clustered epidemic of tuberculosis in this high school and provide scientific basis for improving continuously implementation of tuberculosis control strategies in schools. Methods Complying with the specific requirements of Shantou Health Bureau of Guangdong Province on handling this affair,close contacts who were deemed to be in close contact with index case in terms of study,living space and interpersonal interaction were screened. Suspicious symptom examination,chest x⁃ray examination and skin test of tuberculin(PPD)were performed among these close con⁃ tacts. For diagnosing comprehensively to tuberculosis,interferon gamma release assay(IGRA),CT image examina⁃ tion,sputum smear acid⁃fast staining microscopic examination,isolation and species identification of mycobacteria and Xpert MTB/RIF molecular detection were performed for any patients with any abnormal results from the above⁃ mentioned screening process. In order that the transmission relationships were established correctly bases on genic cluster patterns of MIRU ⁃ VNTR,15 ⁃ loci MIRU ⁃ VNTR (ETRA,ETRB,ETRC,ETRE,ETRF,MIRU10,MIRU20,MIRU26,MIRU39,MIRU40,Mtub04,Mtub21,Mtub38,Oub11b,and Qub26)of Mycobacterium tuberculosis from cases with tuberculosis were detected and analyzed. Results The first,the index case had presented these lesions such as patchy,speckled and streak ⁃like increased density images in the upper lobe of both lungs and multiple cavities of which the largest was about 2.1 cm × 1.7 cm in the upper lobe of left lung, and his laboratorial results of isolation and molecular detection of pathogen were positive. The second,15 other cases with pulmonary tuberculosis were found following three months after the discovery of the index case in this school.Among these cases,there were clinical symptoms in 3 cases,sputum⁃smear suspicious positive in 3 cases, pathogen isolation culture positive in 9 cases and molecular detection positive in 7 cases respectively.As to close contact with index case,10 cases had close spatial contact cluding the same classroom,dormitory or evening self⁃ study classroom and 4 cases direct or indirect interpersonal contact while one case had no clear clues of close con⁃ tact.The third,genotyping laboratory results demonstrated that the copy number patterns of 15⁃loci MIRU ⁃VNTR were identical in eight isolates among nine isolates,of which one isolate was not obtained genotyping result.Finally, assuming“PPD skin test ≥ 5 mm”was regard as the criterion of latent tuberculosis infection,252 out of 409 patients were positive and the latent infection rate was 61.61%.There was a significant difference in latent infection rate between the students from class of the index case and the students from classes of other cases(100% vs. 56.58%, χ2 = 30.781,P < 0.001). However,there is no significant difference between the following population groups: male vs.female,resident students vs.day students,students from different floors and students from the same side of same vs.students from the opposite side of same(P > 0.05). Conclusions This clustered epidemic of tuberculo⁃ sis was caused by the same infectious source,which caused much higher latent tuberculosis infection rate than that of the general population.It is urgent to strengthen the effective implementation of school tuberculosis control measures because the main reason causing this affair is serious lack of management of school tuberculosis control. 
Clinical Advances
Research progress of pembrolizumab in the treatment of castration ⁃ resistant prostate cancer 
HUANG Wei, FU Weijin, ZHANG Mingjin, YANG Xiaoli.
2023, 39(11):  1376-1382.  doi:10.3969/j.issn.1006⁃5725.2023.11.010
Abstract ( 235 )  
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Prostate cancer(PCa)is most common among American and European elder males. Despite hav⁃ ing the initial effectiveness of radical surgery and androgen deprivation therapy at the preliminary stage,prostate cancer eventually develops into castration⁃resistant prostate cancer(CRPC),which results in a poor prognosis. In recent years,base⁃PD⁃1 inhibitor pembrolizumab has been successfully applied in treating multiple solid tumors, which also has achieved primary efficacy in treating CRPC. This paper summarizes the current status and existing problems of pembrolizumab in the clinical trials of CRPC. 
Basic Research
Shikonin inhibits collagen deposition of human hypertrophic scar fibroblasts via PTEN 
TANG Yuting, MA Fang, HE Xi, WANG Jianjun, YANG Anning, WU Kai, JIAO Yun, BAI Zhigang, JIANG Yideng, SHEN Jiangyong.
2023, 39(11):  1382-1388.  doi:10.3969/j.issn.1006⁃5725.2023.11.011
Abstract ( 203 )  
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Objective To investigate the effect of shikonin on the collagen deposition of human hypertro⁃ phic scar fibroblasts from the perspective of PTEN. Methods Hematoxylin ⁃ eosin staining and Masson staining were used to identify hypertrophic scar tissue. Immunofluorescence was used to identify fibroblasts. The relative expression level of PTEN was detected by Western blot at the tissue level. Hypertrophic scar fibroblasts were ran⁃ domly divided into dimethyl sulfone group,shikonin group,control group,si ⁃NC group,shikonin+ si ⁃NC group and shikonin+si⁃PTENC group,western blot were used to detect the expression of PTEN and collagen⁃related proteins(Col1,Col3 and α⁃SMA)at protein levels,respectively. Results Compared with normal skin,PTEN was lower expressed in hypertrophic scar(P < 0.05). shikonin was dissolved in dimethyl sulfone to make drug solution at IC50 concentration(13.46 μmol/L),which was used for human hypertrophic scar fibroblasts cell culture for 24 hours,shikonin down⁃regulated the expression levels of Col1,Col3 and α⁃SMA in human hypertrophic scar fibro⁃ blasts,while up⁃regulated the expression of PTEN(P < 0.05). Transfected with si⁃PTEN,the expressions of Col1, Col3 and α⁃SMA in human hypertrophic scar fibroblasts were increased compared with the si⁃NC group(P < 0.05). After co⁃transfection with shikonin + si⁃PTEN,the expressions of Col1,Col3 and α⁃SMA in human hypertrophic scar fibroblasts were increased compared with shikonin + si⁃NC group(P < 0.05). Conclusion Shikonin can inhibit collagen deposition in hypertrophic scar fibroblasts by up⁃regulating PTEN expression. 
Silent information regulator 2⁃related enzyme 3 regulates autophagy to alleviate H2O2⁃induced apoptosis of alveolar type Ⅱ epithelial cells 
LIAO Zhenliang, FENG Banghai, REN Yingcong, LIU Junya, ZHENG Jie, MEI Hong, QIN Song. ​
2023, 39(11):  1389-1395.  doi:10.3969/j.issn.1006⁃5725.2023.11.012
Abstract ( 176 )  
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Objective To investigate the role of sirtuin 2⁃related enzyme 3(SIRT3)regulating mitophagy in H2O2⁃induced apoptosis of alveolar type Ⅱ epithelial cells. Methods The mouse type Ⅱ alveolar epithelial cell line(MLE ⁃12)in logarithmic growth period was used to establish MLE ⁃ 12 cell apoptosis model with 0.5 mmol/L H2O2. The model was divided into normal control group,H2O2 injury group,H2O2+SIRT3 group,and H2O2+SIRT3 silence group. CCK8 was used to detect the proliferative activity of cells in each group;SOD,MDA and T⁃AOC kit were used to detect the level of SOD,MDA and T⁃AOC;The mRFP⁃GFP⁃LC3 autophagy double label system was constructed,and the autophagy level was observed by laser confocal microscopy;The changes of mitochondrial membrane potential and ROS level were observed by laser confocal microscopy;Western blot was used to detect the expression level of SIRT3,Bcl⁃2,Bax and LC3B. Results Compared with those in the normal controls,the level of MDA and ROS and autophagosome and autolysosomes were increased in the H2O2 injury,H2O2 + SIRT3 and H2O2 + SIRT3 silencing group(P < 0.05). Reduced cell viability,SOD,T ⁃AOC levels,and mitochondrial membrane potential(P < 0.05),reduced protein expression of SIRT3 and Bcl2(P < 0.05),and increased Bax and LC2Ⅱ protein expression(P < 0.05)were observed,particularly significantly in the H2O2 + SIRT3 silencing group. Compared with those in the H2O2 injury group,the level of MDA and ROS and the number of autophagosome and autolysosome points were decreased in the H2O2 + SIRT3 and H2O2 + SIRT3 silencing group(P < 0.05); increased cell viability,the level of SOD and T⁃AOC,and mitochondrial membrane potential(P < 0.05),elevated expression of SIRT3 and Bcl2 protein(P < 0.05),reduced expression of Bax and LC2Ⅱ proteins were observed (P < 0.05). Conclusion SIRT3 can alleviate H2O2⁃induced alveolar type Ⅱ epithelial cell damage by inhibiting autophagy,oxidative stress and apoptosis. 
Promotion of vascular calcification through sterol ⁃ O ⁃ acyltransferase 1 ⁃ mediated mitochondrial division 
XU Ting, YANG Li, HUANG Wei, YU Hao.
2023, 39(11):  1396-1402.  doi:10.3969/j.issn.1006⁃5725.2023.11.013
Abstract ( 229 )  
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Objective To clarify the role of mitochondrial division mediated by sterol O⁃acyltransferase 1 (SOAT1)in vascular calcification(VC). Methods Mouse vascular smooth muscle cells(VSMCs)were divided into four groups:si⁃NC + Con(SOAT1 negative control siRNA transfected into VSMCs),si⁃NC + β⁃GP(SOAT1 negative control siRNA transfected into VSMCs),si⁃SOAT1 + Con(SOAT1 siRNA transfected into VSMCs)and Si⁃SOAT1 + β. CCK⁃8,wound healing test and alizarin red staining were performed to evaluate the proliferation, migration and osteogenic differentiation of VSMCs. The mitochondrial morphology and oxidative stress level of VSMCs were analyzed. Twenty C57BL/J mice were randomly divided into four different groups,with 5 mice in each group:control group(Ctrl group),5/6 nephrectomy plus phosphate diet treatment group(NTP group),NTP + si⁃NC group and NTP + si⁃SOAT1 group. The expression of RUNX2,SOAT1 and α⁃SMA in mouse aorta was analyzed by immunofluorescence. Results In different time periods(0,1,3,5,7 and 14 d)of β⁃GP culturation,the protein level of osteogenic markers RUNX2 and SOAT1 in VSMCs gradually increased in a time ⁃dependent manner(P < 0.05),and the contraction marker α⁃ SMA in VSMCs gradually decreased in a time ⁃ dependent manner(P < 0.05). Compared with those in si⁃NC + Con group,the cell proliferation rate,the ratio of EdU positive cells,cell migration and alizarin red staining intensity increased significantly in si⁃NC + β⁃GP group(P < 0.05). Compared with those in si⁃NC + β⁃GP group,the cell proliferation rate,EdU positive cell ratio,cell migration and alizarin red staining intensity decreased significantly in si⁃SOAT1 + β⁃GP group(P < 0.05). The protein level of RUNX2 and SOAT1 in si⁃SOAT1 + β⁃GP group were significantly lower than that in si⁃NC + β⁃GP group(P < 0.05),and the protein level of α⁃SMA was higher than that in si⁃NC + β⁃GP group(P < 0.05). Compared with those in si⁃NC + Con group, the mitochondrion breakage and ROS level produced by mitochondria increased significantly in si ⁃ NC + β ⁃ GP group(P < 0.05). Compared with those in si⁃NC + β⁃GP group,the mitochondrion breakage and ROS level produced by mitochondrion decreased significantly in si⁃SOAT1 + β⁃GP group(P < 0.05). Compared with those in Ctrl group, the positive area of alizarin red staining and the expression of RUNX2 and SOAT1 protein in aorta in NTP group and NTP + si⁃NC group increased significantly(P < 0.05). Compared with those in NTP + si⁃NC group,the posi⁃ tive area of alizarin red staining and the expression of RUNX2 and SOAT1 protein in aorta decreased significantly in NTP + si ⁃SOAT1 group(P < 0.05). Conclusion High concentration of phosphate exposure can induce VC, which may be related to mitochondrial division mediated by SOAT1. 
Effects of lidocaine on the malignant biological behavior of glioma cells through SHH/GLI signaling pathway 
MA Jun, XIANG Mei.
2023, 39(11):  1403-1408.  doi:10.3969/j.issn.1006⁃5725.2023.11.014
Abstract ( 207 )  
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Objective To investigate the impact of lidocaine(Lid)on malignant biological behavior of glioma cells by regulating SHH/GLI signal pathway. Methods The U87 cells were divided into U87 group,L⁃Lid group,M⁃Lid group,H⁃Lid group,PM group,and H⁃Lid + PM group. No treatment was performed on U87 cells in L⁃Lid group,M⁃Lid group,and H⁃Lid group. U87 cells were treated with 5,10,and 15 mmol/L Lid,respectively, while PM group was treated with 1 mmol/L Lid μ U87 cells were treated with mol/L of SHH/GLI signal pathway activator PM,while H⁃Lid + PM group was treated with 15 mmol/L Lid and 1 μ The U87 cells were co treated with mol/L of PM. CCK8 was applied to detect U87 cell proliferation;flow cytometry was applied to detect U87 cell apoptosis;Transwell was applied to detect the migration and invasion abilities of U87 cells;Western blot was applied to detect the expression of SHH/GLI protein and apoptosis protein;the tumor⁃bearing mouse model was applied to verify the effect of Lid on U87 cell transplanted tumor. Results Compared with U87 group,the OD value,num⁃ bers of U87 cell migration and invasion,the protein levels of Bcl⁃2,SHH and GLI3,and tumor volume of mice in L⁃Lid group,M⁃Lid group and H⁃Lid group decreased obviously in turn(P < 0.05),the apoptosis rate and Bax protein level increased obviously in turn(P < 0.05);the OD value,numbers of U87 cell migration and invasion,the protein levels of Bcl⁃2,SHH and GLI3,and tumor volume of mice in PM group were obviously increased(P < 0.05),the apoptosis rate and Bax protein level decreased obviously(P < 0.05);PM eliminated the inhibitory effect of H⁃Lid on the malignant biological behavior of U87 cells. The survival number of transplanted tumor mice increased after Lid treatment,while the survival number of transplanted tumor mice decreased after PM treatment,and the number in H⁃Lid+PM group was the same as that in L⁃Lid group. Conclusion Lid may inhibit the proliferation of U87 cells, promote cell apoptosis,and then inhibit the progression of glioma by down⁃regulating SHH/GLI signal pathway. 
Clinical Research
Effects of different anesthesia techniques on perioperative inflammatory stress and immune function in elderly patients undergoing total hip arthroplasty 
WU Wenqi, DENG Lian, MA Wuhua, CAI Chengyi.
2023, 39(11):  1409-1415.  doi:10.3969/j.issn.1006⁃5725.2023.11.015
Abstract ( 259 )  
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Objective To compare the effects of nerve block combined with laryngeal mask anesthesia, combined spinal⁃epidural anesthesia,and general anesthesia on perioperative inflammatory stress and immune func⁃ tion in elderly patients undergoing total hip arthroplasty. Methods Totally 60 patients who underwent unilateral total hip arthroplasty,including 21 males and 39 females,aged 63 ~ 80 years,with a BMI of 17 ~ 35 kg/m2 ,ASA Ⅱ or above,were randomly divided into nerve block combined with laryngeal mask anesthesia group(group N),combined spinal⁃epidural anesthesia group(group E),and general anesthesia group(group G),with 20 cases in each group. Group N was given lumbosacral plexus nerve block combined with laryngeal mask general anesthesia; group E combined spinal ⁃epidural anesthesia,and group G general anesthesia. After the operation,each group adopted patient ⁃controlled intravenous analgesia(PCIA). Blood samples of patients in each group were collected before surgery,1 hour and 24 hours after surgery. Enzyme ⁃linked immunosorbent assay(ELISA)was used to detect plasma IL⁃10,cortisol,CRP,IL⁃4,and IFN⁃γ level. VAS pain score was recorded 24 h before surgery,12 h and 24 h after surgery. Results Compared with that in group G,the dose of remifentanil in group N was reduced (P < 0.05). There was no statistical difference in ephedrine and atropine use among the three groups(P > 0.05). Compared with those in group G,the plasma IL⁃4 level of groups N and E were reduced after 24 hours of surgery (P < 0.05),and the IFN⁃γ/IL⁃4 ratio increased(P < 0.05);plasma cortisol level decreased 1 hour after surgery (P < 0.05),and plasma IL⁃10,cortisol,and CRP level decreased 24 hours after surgery(P < 0.05). Compared with that of group G,the VAS score of group N decreased 12 hours after surgery,showing clinical significance (P < 0.05). Conclusion Compared with general anesthesia,nerve block combined with laryngeal mask anesthesia and spinal⁃epidural anesthesia can reduce the expression of immune and inflammatory stress⁃related cytokines after total hip replacement surgery in elderly patients,among which nerve block combined with laryngeal mask anes⁃ thesia has better analgesic effect. 
Evaluation of safety and efficacy of simultaneous surgery for portal hypertension with hepatocellular carci⁃ noma 
WEN Jing, HE Rong, ZHANG Hongwei, XIONG Qiqiu, JIA Zhe, ZHANG Ke.
2023, 39(11):  1416-1421.  doi:10.3969/j.issn.1006⁃5725.2023.11.016
Abstract ( 205 )  
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Objective To evaluate the safety and long⁃term efficacy of devascularization and hepatectomy or radiofrequency ablation (RFA)to treat portal hypertension (PHT)with hepatocellular carcinoma (HCC). Method Retrospective analysis of clinical data of 490 patients,including 280 cases of devascularization and hepatectomy(hepatectomy group)and 210 cases of devascularization and RFA(RFA group). The postoperative complications,overall survival rate andrecurrence free survival rate were observed.To analyze the risk factors of postoperative survival and recurrence of HCC. Results There were no cases of encephalopathy,liver failure and surgical deaths. The overall survival rates at 1,3,5 years after surgery were 94.1%,81.5%,74.2% in the hepatectomy group,and 86.3%,72.0%,37.8% in the RFA group(P < 0.001). Age,surgical method,tumor staging,and Child⁃ Pugh grading are independent risk factors for overall survival. The 1st,3rd,5th year recurrence free survival rates were 69.2%,54.4%,and 40.6% respectivelyin the hepatectomy group,and 58.7%,28.5%,and 18.5% respectively in the RFA group(P < 0.001). Age,tumor size,Child⁃Pugh grade,and AFP are independent risk factors for recur⁃ rence free survival. Conclusion Simultaneous surgery is a safe and effective treatment for PHT with HCC. The long⁃ term effect of liver resection is better. Devascularization and liver resection should be preferred in practice. 
Correlation between serum FGF2,TRPC1 levels and psychiatric symptoms in patients with schizophrenia 
ZHANG Xiaoming, GUO Bin, LIU Yanru, ZHANG Fangfang, LIU Huaqing, WANG Zhiren.
2023, 39(11):  1422-1426.  doi:10.3969/j.issn.1006⁃5725.2023.11.017
Abstract ( 151 )  
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Objective To investigate the expression of fibroblast growth factor 2(FGF2)and transient receptor potential channel 1(TRPC1)in patients with schizophrenia and their correlation with psychiatric symptoms. Methods A total of 200 schizophrenic patients admitted to the hospital from July 2019 to June 2022 and 200 normal people who underwent physical examination were selected as the observation group and control group,respectively. General data were collected and serum FGF2 expression levels were detected by enzyme ⁃linked immunosorbent assay. The TRPC1 level was detected by WD ⁃3000 automatic hematology analyzer and immunocolorimetry. The Positive and Negative Symptom Scale(PANSS)was used to evaluate psychiatric symptoms. The correlation between FGF2,TRPC1 and psychiatric symptoms was analyzed by Pearson method. The diagnostic value of serum FGF2 and TRPC1 levels in schizophrenia was evaluated by receiver operating characteristic(ROC)curve. Results The expression level of TRPC1 in serum of observation group was lower than that of control group ,and the expression level of FGF2 was higher than that of control group(P < 0.05);The total PANSS score,positive score,negative score and general symptom score in observation group were higher than those in control group(P < 0.05);serum FGF2 expression in patients with schizophrenia was positively correlated with total PANSS score,positive score, negative score and general symptom score,while TRPC1 expression was negatively correlated with total PANSS score,positive score,negative score and general symptom score(P < 0.05). The area under the ROC curve(AUC) of serum FGF2 and TRPC1 levels in predicting schizophrenia patients was 0.928 and 0.911,respectively,the corresponding sensitivity was 84.00% and 89.50%,and the specificity was 89.00% and 86.50%,respectively;the AUC of the two combined detection of schizophrenia patients was 0.969,and the sensitivity and specificity were 94.50% and 90.00%,respectively. Conclusion The serum level of FGF2 and TRPC1 in patients with schizophrenia is significantly increased,and the serum levels of FGF2 and TRPC1 are closely related to the psychiatric symptoms of patients. 
Retrospective analysis of the changes of bone tunnel diameter and residual length after old injury and fresh injury of anterior cruciate ligament injury 
HOU Feiyi, LI Shensong, ZHANG Lian, YANG Qinxu, YANG Qiaoqiao. ​
2023, 39(11):  1427-1432.  doi:10.3969/j.issn.1006⁃5725.2023.11.018
Abstract ( 173 )  
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Objective To investigatey the changes of tibial and femoral bone tunnels and the influence of residual length after old anterior cruciate ligament injury and fresh injury,and to evaluate its clinical efficacy. Methods A total of 320 patients with anterior cruciate ligament injury admitted to our hospital from January 2020 to January 2021 were selected and assigned to fresh injury group(≤ 3 months after injury,n = 160)and old injury group(> 3 months after injury,n = 160 ). CT was performed at different time periods. The changes of tibial and femoral bone tunnels in the two groups were measured,and the IKDC,Lysholm and Tenger scores of the knee joint,the recovery of knee proprioception and the healing of tendon and bone by nuclear magnetic resonance were monitored. Results The residual length of the fresh injury group was significantly better than that of the old injury group(P < 0.05). At 6 months after operation ,the tibial and femoral bone tunnels of the two groups were enlarged. The expansion of the femoral bone tunnel in the fresh injury group was smaller than that of the old injury group. There was a statistical difference between the two groups(P < 0.05),but there was no statistical difference between the two groups(P > 0.05). At 1 year after operation,the tibial and femoral bone tunnels were enlarged at the same time. The expansion of the bone tunnel in the fresh injury group was significantly smaller than that in the old injury group. There was a statistical difference between the groups(P < 0.05). Compared with the old injury group,the IKDC,Lysholm and Tenger scores of the fresh injury group were significantly better than those of the old injury group(P < 0.05). There was no significant difference in knee proprioception between the two groups at 6 months after operation(P > 0.05). At 12 months after operation,the fresh injury group was significantly better than the old injury group. There was significant difference between the two groups(P < 0.05). Conclusion Early anterior cruciate ligament reconstruction(≤ 3 months)could better preserve the stump,prevent the expansion of the tibial femoral tunnel and restore knee function. 
Clinical observation of Yoga in the recovery of overall pelvic floor function in postpartum women
LIU Ji⁃ angling, ZHOU Jiahe, XU Qiuyi, LI Li.
2023, 39(11):  1433-1439.  doi:10.3969/j.issn.1006⁃5725.2023.11.019
Abstract ( 156 )  
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Objective This study aims to explore the effect of yoga exercise on the recovery of pelvic floor function and quality of life in postpartum women. Methods A total of 182 puerperas diagnosed with pelvic floor dysfunction who were diagnosed with pelvic floor dysfunction in our hospital from September 2021 to March 2022 were selected as the research objects. They were randomly divided into a yoga group and a control group according to 1∶1. Combined with yoga exercise,the control group only adopted health education. The main observation index of this study is pelvic floor muscle strength,and the second observation indexes are pelvic floor electrophysiological index,pelvic organ prolapse scale,body mass index,waist circumference,pelvic organ prolapse and urinary incontinence sexual function questionnaire(PISQ⁃12)Changes in the score,urinary incontinence impact question⁃ naire(IIQ⁃7)score,and VAS scale score. Results After the intervention,the pelvic floor muscle strength of the yoga group was significantly improved compared with the control group(P < 0.05);the vaginal dynamic pressure value of the yoga group was better than that of the control group(P < 0.05);the improvement degree of pelvic organ prolapse better than the control group(P < 0.05);the body mass index decline in the yoga group was higher than that in the control group(P < 0.05);the scores of the three quality of life questionnaires in the yoga group were better than those in the control group(all P < 0.05). Conclusion Yoga can significantly improve the recovery of postpartum women′s overall pelvic floor function. It is not affected by venue,time,and equipment. It is conve⁃ nient and easy to implement,and it is worthy of clinical promotion.
Drugs and Clinic Practice
Associations of μ ⁃ opioid receptor gene polymorphism with pain sensitivity and opioid dosage in patients with postherpetic neuralgia 
ZHU Kun.
2023, 39(11):  1440-1443.  doi:10.3969/j.issn.1006⁃5725.2023.11.020
Abstract ( 180 )  
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Objective To explore the associations of the polymorphism of μ ⁃ opioid receptor gene (OPRM1)with pain sensitivity and opioid dosage in patients with postherpetic neuralgia(PHN). Methods The clinical data of 170 herpes zoster(HZ)patients who visited the pain clinic of our hospital from January 2019 to July 2022 were reviewed,90 of them put in the PHN group and 80 put in the non⁃PHN group according to the pres⁃ence or absence of postherpetic neuralgia 3 months after HZ onset. The factors influencing the occurrence of PHN were analyzed by Logistic regression analysis. The two groups were compared in terms of 48h opioid dosage,sleep quality score and state trait anxiety score among different genotypes of PHN patients with moderate and severe pains. #The independent risk factors for PHN were found to include initial treatment > 72 hours,severe pain in acute stage and genotype GG. The frequency of GG genotype distribution was significantly increased across the PHN mild pain,moderate pain and severe pain groups. As compared with the PHN moderate group,the 48 h dos⁃age of opioids in the patients with different genotypes in the PHN moderate and severe pain group were significantly increased(P < 0.05),with the highest in the GG genotype patients. Conclusion The independent risk factors for PHN are initial treatment >72 h,acute severe pain and genotype GG. The polymorphism of OPRM1 gene is the genetic factor that causes individual differences of opioid pharmacodynamics in PHN patients. 
Medical Examination and Clinical Diagnosis
Application of indocyanine green near ⁃ infrared fluorescence imaging in breast conserving surgery for breast cancer 
JIAO Wei, ZHAO Kai, WANG Zheng, CHEN Bin, WANG Yabing.
2023, 39(11):  1444-1450.  doi:10.3969/j.issn.1006⁃5725.2023.11.021
Abstract ( 205 )  
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Objective To assess the value of near⁃infrared fluorescence imaging combined with indocyanine green contrast agents in breast ⁃ conserving surgery for breast cancer. Methods The clinical data on 155 patients with breast cancer who had received surgical treatment in Yijishan Hospital of Wannan Medical College from January 2020 to April 2022 were analyzed. Of those patients,55 were labeled with indocyanine green and underwent surgery under the guidance of anear⁃infrared fluorescence imaging system(fluorescence group)and 100 receivedconventional breast conserving surgery(control group). The clinical characteristics,diagnostic rate,and margin status were com⁃ pared between the two groups,and the role of near⁃infrared fluorescence imaging in intraoperative tumor localization and margin determination was explored. Results The mean resection time was(13.85 ± 3.39)min in the fluores⁃ cence group,which was faster than(18.78 ± 4.81)min in the control group(P < 0.05). The positive rate of first inci⁃ sion margin was significantly lower in the fluorescence group than in thecontrol group(3.6%vs. 19.0%,P < 0.05). Fluorescence was detectablein primary tumors in all thepatients. The average fluorescence intensity was(229.84 ± 22.03),(144.02 ± 14.12)and(108.64 ± 9.76)arbitrary units(AU)in tumor,peritumoral and normal tissues(P < 0.05). The background ratio of tumor fluorescence signal to peritumoral tissue and tonormal tissue was(1.60 ± 0.17) and(2.13 ± 0.25),respectively(P < 0.05). The sensitivity and specificity of near⁃infrared fluorescence imaging forassessing the incisionmargin were 86.66% and 94.23%,respectively. Conclusions Intraoperative application of near⁃infrared fluorescence imaging for tumor localization can effectively avoid excessive resection of normal tissues. It has high sensitivity and specificity for the evaluation of cutting edge statusand can significantly reduce the positive.rate of cutting edge and shorten the surgical duration. Near⁃infrared fluorescence imaging technology is safe and feasible in breast⁃conserving surgery for breast cancer and has important guiding value. 
Modernization of Traditional Chinese Medicine
Clinical study on the treatment of cervical spondylosis of vertebral artery type with functional exercise of respiratory mode reconstruction combined with ginger separated moxibustion 
LAI Chunbai, LI Shiliang, ZHONG Yuehai, LIU Cuiqing, MIAO Zuoxiong.
2023, 39(11):  1451-1456.  doi:10.3969/j.issn.1006⁃5725.2023.11.022
Abstract ( 172 )  
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Objective To observe the effects of functional exercise for respiratory pattern reconstruction combined with different amounts of ginger separated moxibustion on symptoms such as dizziness,neck and shoul⁃ der pain,and headache in patients with cervical spondylosis of vertebral artery type,in order to provide a safe and effective treatment for clinical treatment of cervical spondylosis of vertebral artery type. Methods 120 patients with cervical spondylosis of vertebral artery type who met the inclusion criteria were randomly divided into four groups: Treatment group 1(conventional acupuncture + electroacupuncture + massage + respiratory mode reconstruction functional exercise combined with ginger separated moxibustion for 3 zhuang),treatment group 2(conventional acupuncture + electroacupuncture + massage + respiratory mode reconstruction functional exercise combined with ginger separated moxibustion for 6 zhuang),and treatment group 3(conventional acupuncture+electroacupuncture+ massage + respiratory mode reconstruction functional exercise combined with ginger separated moxibustion for 9 zhuang),and the control group(conventional acupuncture+electroacupuncture+massage+warm moxibustion)had 30 cases in each group. The scores of the cervical vertigo symptom and function scale(ESCV)and visual analogue scale(VAS)were recorded before and after treatment,as well as at the first and third months following treatment. Results Before treatment,there was no significant difference in ESCV and VAS scores among the four groups (P > 0.05)After treatment,ESCV scores in groups 1,2,and 3 were higher than those in the control group(all P < 0.05),with group 3 having the highest(P < 0.05);The VAS scores of treatment groups 1,2,and 3 were lower than those of the control group(all P < 0.05),with group 3 having significantly lower VAS scores than the other three groups(P < 0.05). Conclusion Functional exercise for respiratory pattern reconstruction combined with ginger separated moxibustion can significantly improve symptoms such as dizziness,neck and shoulder pain,and headache in patients. The greater the amount of moxibustion,the better the efficacy. This therapy is safe and has no side effects,and is worthy of clinical promotion. 
Reviews
Mechanism of glucocorticoid resistance in multiple myeloma 
ZHANG Ling, JIN Chenghao, KONG Chun⁃ fang.
2023, 39(11):  1457-1460.  doi:10.3969/j.issn.1006⁃5725.2023.11.023
Abstract ( 234 )  
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Multiple myeloma(MM)is a malignant clonal cancer of plasma cell characterized by overpro⁃ duction of abnormal plasma cells in the bone marrow and skeletal destruction. Its incidence rate ranks the second among all malignant hematologic diseases. With a widespread usage of protease inhibitors,immunomodulators, corticosteroids and other chemicals,the survival rate of MM has substantially improved in the past 20 years. Corti⁃ costeroids are the first⁃line drug of MM combination chemotherapy,but almost all MM will relapse or become drug resistance in later treatment. There fore,exploring the mechanism of MM′s drug resistance to corticosteroids and enhancing MM′s sensitivity to dexamethasone will provide a a improved treatment plan to the patients prognosis and deeper understanding of MM.