1.Research progress on strategies to target intestinal microbiota to improve drug resistance in tumor immunotherapy
Hui-ling LI ; Bi-qing LIU ; Ying-nan FENG ; Xin HU ; Lan ZHANG ; Xian-zhe DONG
Acta Pharmaceutica Sinica 2025;60(2):260-268
A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.
2.Clinical trial of brexpiprazole in the treatment of adults with acute schizophrenia
Shu-Zhe ZHOU ; Liang LI ; Dong YANG ; Jin-Guo ZHAI ; Tao JIANG ; Yu-Zhong SHI ; Bin WU ; Xiang-Ping WU ; Ke-Qing LI ; Tie-Bang LIU ; Jie LI ; Shi-You TANG ; Li-Li WANG ; Xue-Yi WANG ; Yun-Long TAN ; Qi LIU ; Uki MOTOMICHI ; Ming-Ji XIAN ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(5):654-658
Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50%(140 cases/184 cases)and 82.40%(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P>0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P>0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P>0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00%vs.64.50%,P>0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.
3.Study on Traditional Chinese Medicine Syndrome Characteristics of 1676 Heart Failure Inpatients: A Cross-Sectional Survey Based on Real-World Electronic Medical Record Information
Yi DU ; Zheng LI ; Guanlin YANG ; Shuqi DONG ; Wenshuai HUANG ; Nanxing XIAN ; Puyu GUO ; Jiajie QI ; Bohang CHEN ; Xin XU ; Zhe ZHANG ; Yi YANG
Journal of Traditional Chinese Medicine 2024;65(3):299-307
ObjectiveTo analyse the clinical characteristics of different traditional Chinese medicine (TCM) syndromes in patients with heart failure based on information from electronic medical record. MethodsA cross-sectional study was conducted to collect clinical data of all inpatients with heart failure in the Department of Cardiology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from January 1, 2019 to December 31, 2020. A database of clinical TCM data was established to explore the characteristics of clinical data of basic information, syndromes and syndrome element types, and biochemical indexes. The distribution of TCM syndromes and syndrome elements in heart failure patients were also analysed, and the basic information and biochemical indexes of the patients with top 7 different TCM syndrome types were compared. ResultsA total of 1676 inpatients with heart fai-lure were included. The top 7 TCM syndromes of heart failure were syndrome of phlegm turbidity and blood stasis (477 cases, 28.46%), syndrome of qi deficiency and blood stasis (439 cases, 26.19%), syndrome of qi deficiency and blood stasis with water retention (274 cases, 16.35%), syndrome of yang deficiency with water retention (145 cases, 8.65%), syndrome of qi and yin deficiency (104 cases, 6.21%), syndrome of qi and yin deficiency with blood stasis (80 cases, 4.77%), syndrome of heart yang deficiency (59 cases, 3.52%). Among the 1676 patients, 6 syndrome elements accounted for more than 5%. Blood stasis accounted for the highest proportion of TCM syndrome element type (1292 cases, 77.09%), followed by qi deficiency (919 cases, 54.83%), phlegm (498 cases, 29.71%), water retention (434 cases, 25.89%), yang deficiency (215 cases, 12.82%) and yin deficiency (191 cases, 11.40%). Among the 1676 patients, 1308 cases of acute heart failure mainly showed syndrome of phlegm turbidity and blood stasis (386 cases, 29.51%), and 368 of chronic heart fai-lure mainly showed syndrome of qi deficiency and blood stasis (118 cases, 32.07%). Patients with syndrome of phlegm turbidity and blood stasis had the shortest disease duration of 0.3 months, while those with syndrome of heart yang deficiency had the longest disease duration of 15 months. The proportion of syndrome of phlegm turbidity and blood stasis was the highest in patients with heart failure combined with coronary artery disease, the proportion of syndrome of qi deficiency and blood stasis with water retention was the highest in patients with heart failure combined with atrial fibrillation, and the proportion of patients with syndrome of qi deficiency and blood stasis with water retention and syndrome of yang deficiency with water retention in those applying diuretics during the hospital stay was the highest with more than 86%. The different 7 TCM syndromes showed statistically difference in patients with complications including coronary artery disease, old myocardial infarction, atrial fibrillation, pre and post-admission medication usage including intravenous vasodilators, cardiac stimulants, diuretics, and level of blood chloride, blood urea, blood creatinine, blood bicarbonate, blood albumin, and blood total bilirubin (P<0.05). ConclusionThe most common TCM syndromes in patients with heart failure are syndrome of phlegm turbidity and blood stasis and syndrome of qi deficiency and blood stasis. Different TCM syndromes have different characteristics in gender, disease complications, medication before and after admission, and blood indexes.
4.Clinical Value of Detecting ABL Kinase Domain Mutations in Patients with Chronic Myeloid Leukemia Based on High-Throughput Sequencing Technology
Ling ZHOU ; Jun-Liang WANG ; Xian-Wei WANG ; Yang-Wei LI ; Zhe ZOU ; Yan-Li ZHANG ; Xiao-Dong LYU
Journal of Experimental Hematology 2024;32(1):262-268
Objective:To compare the efficacy and clinical value of high-throughput sequencing(HTS)and Sanger sequencing in detecting ABL kinase domain mutations in patients with chronic myeloid leukemia(CML).Methods:A total of 198 samples of 147 CML patients from July 2017 to March 2021 in Henan Cancer Hospital were collected and underwent high-throughput sequencing and Sanger sequencing to detect the mutations in ABL kinase domain,and the relevant clinical data were collected for comparative analysis.Results:The proportion of total mutations and ≥ 2 mutations detected by high-throughput sequencing were significantly higher than those detected by Sanger sequencing(P=0.01;P=0.046).≥ 2 mutations were detected in 22 cases,of which 5 cases(22.7%)had compound mutations.High-throughput sequencing can detect low level mutations that cannot be detected by Sanger sequencing.In 198 samples,25(12.6%)were low level mutations,33(16.7%)were high level mutations and 10(5.1%)were mixed high and low level mutations.In the analysis of related clinical factors,the total mutation rate and the low level mutation rate in the optimal period,failure period and warning period were gradually increased(total mutation rate,P=0.016;low level mutation rate,P=0.005).The mutation rate of the samples with additional chromosomal abnormalities was also significantly increased(P=0.009).The mutation rate of patients who received first-and second-line treatment was significantly lower than that of patients who received third-or higher-line treatment(P=0.006).Analysis based on variant allele frequency(VAF)of the mutation site was helpful to visually evaluate the clonal evolution status of TKI-resistance CML cells.Conclusion:High-throughput sequencing is more sensitive and accurate than Sanger sequencing in mutation detection,which is helpful to accurately and visually evaluate TKI treatment response and optimize treatment strategy for CML.
5.Preliminary study on delaying aging induced thymus degeneration in SAMP6 mice with Bazi Bushen capsule
Zhao-Dong LI ; Yin-Xiao CHEN ; Bo-Yang GONG ; Zhe XU ; Zhi-Xian YU ; Yue-Xuan SHI ; Yan-Fei PENG ; Yu-Hong BIAN ; Yun-Long HOU ; Xiang-Ling WANG ; Shu-Wu ZHAO
Chinese Pharmacological Bulletin 2024;40(6):1186-1192
Aim To explore the improvement effect of Bazi Bushen capsule on thymic degeneration in SAMP6 mice and the possible mechanism.Methods Twenty 12 week old male SAMP6 mice were randomly divided into the model group(SAMP6)and the Bazi Busheng capsule treatment group(SAMP6+BZBS).Ten SAMR1 mice were assigned to a homologous control group(SAMR1).The SAMP6+BZBS group was oral-ly administered Bazi Bushen capsule suspension(2.8 g·kg-1)daily,while the other two groups were orally administered an equal amount of distilled water.After nine weeks of administration,the morphology of the thymus in each group was observed and the thymus in-dex was calculated;HE staining was used to observe the structural changes of thymus tissue;SA-β-gal stai-ning was used to detect thymic aging;flow cytometry was used to detect the proportion of thymic CD3+T cells in each group;Western blot was used to detect the levels of p16,Bax,Bcl-2,and cleaved caspase-3 proteins in thymus;immunofluorescence was applied to detect the proportion of cortical thymic epithelial cells in each group;ELISA was employed to detect IL-7 lev-els in thymus.Results Compared with the SAMP6 group,the thymic index of the SAMP6+BZBS group significantly increased(P<0.05);the disordered thy-mic structure was significantly improved;the positive proportion of SA-β-gal staining significantly decreased(P<0.01);the proportion of CD3+T cells apparently increased(P<0.05);the level of p16 protein signifi-cantly decreased(P<0.05);the level of Bcl-2 pro-tein significantly increased(P<0.05),while the lev-el of cleaved caspase-3 protein markedly decreased(P<0.05);the proportion of cortical thymic epithelial cells evidently increased;the level of IL-7 significantly increased(P<0.01).Conclusions Bazi Bushen capsule can delay thymic degeneration,inhibit cell ap-optosis in thymus and promote thymic cell development in SAMP6 mice,which may be related to increasing the proportion of cortical thymic epithelial cells and promoting IL-7 secretion.
6.Relationship between body mass index and sexual development in Chinese children.
Xiao Qin XU ; Jian Wei ZHANG ; Rui Min CHEN ; Jing Si LUO ; Shao Ke CHEN ; Rong Xiu ZHENG ; Di WU ; Min ZHU ; Chun Lin WANG ; Yan LIANG ; Hui YAO ; Hai Yan WEI ; Zhe SU ; Mireguli MAIMAITI ; Hong Wei DU ; Fei Hong LUO ; Pin LI ; Shu Ting SI ; Wei WU ; Ke HUANG ; Guan Ping DONG ; Yun Xian YU ; Jun Fen FU
Chinese Journal of Pediatrics 2022;60(4):311-316
Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.
Adolescent
;
Body Mass Index
;
Child
;
Child, Preschool
;
China/epidemiology*
;
Cross-Sectional Studies
;
Female
;
Humans
;
Male
;
Obesity/epidemiology*
;
Overweight/epidemiology*
;
Puberty
;
Puberty, Precocious
;
Sexual Development
7.Comparative study between 3D guide plate assisted and free-hand insertion of anterior cervical transpedicular screw.
Jie LI ; Liu-Jun ZHAO ; Min-Zhe ZHENG ; Kai-Feng GAN ; Yi-Lei CHEN ; Zong-Xian FENG ; Ling-Xiao PAN ; Jun-Xiang XU ; Teng-di FAN ; Jing-Yang CHEN ; Feng-Dong ZHAO
China Journal of Orthopaedics and Traumatology 2021;34(1):45-50
OBJECTIVE:
To compare accuracy of anterior cervical pedicle screws between assist of rapid prototyping 3D guide plate and free-hand insertion, and evaluate the safety of two methods.
METHODS:
Eight adult cervical cadaver specimens after formaldehyde immersion, including 4 males and 4 females, aged 32 to 65(40.3±5.6) years old. After X-ray examination to exclude bone damage and deformity, 4 of them (3D guide plate group) randomly selected were for CT scan to obtain DICOM format data, and the data was imported into Mimics software for model, designed the ideal entry point and nail path for anterior cervicaltranspedicular screw (ATPS). After obtaining the personalized guide plate of the nail channel, it was exported as STL data, and the individual guide plate was printed by rapid prototyping and 3D printing technology. In turn, with the assistance of 3D guide plates, one-to-one personalized ATPS screws were placed on the four lower cervical cadaver specimens. Another 4 (free-hand group) lower cervical cadaver specimens were implanted with ATPS screws using free-hand technique. All specimens were performed CT thin-layer scanning and three-dimensional reconstruction after operation. The Tomasino method was used to evaluate the safety of the screws on the CT cross-sectional and sagittal images, to determine whether there was a cortical puncture of the lower and inner edges of the pedicle. According to the CT rating results, gradeⅠandⅡwere safe, and grade Ⅲ- Ⅴ were dangerous.And the accuracy of screws was recorded and analyzed between two groups.
RESULTS:
Two screws were inserted in each segment from C
CONCLUSION
The 3D printing rapid prototyping guide plate assisted insertion of the anterior cervical pedicle screw can significantly improve the accuracy and safety, and provide a theoretical basis for further clinical application.
Adult
;
Aged
;
Bone Plates
;
Cervical Vertebrae/surgery*
;
Cross-Sectional Studies
;
Female
;
Humans
;
Male
;
Middle Aged
;
Pedicle Screws
;
Printing, Three-Dimensional
8.Research on the influence of 12-week basic load resistance training on the physical fitness of flight students in an aviation school.
Zhe JI ; Hai-Tao ZHOU ; Zhi-Kang ZOU ; Xian GUO ; Xin ZHANG ; Hui CAO ; Zhi-Dong JIANG ; Xiang REN ; An-Li WANG ; Jian-Min CAO
Chinese Journal of Applied Physiology 2021;37(5):519-522
9.Epidemic trend of hepatitis B in 18 ethnic minorities of Yunnan Province from 2009 to 2018
Zhe DONG ; Wen-yu KANG ; Wen YU ; Lin XU ; Xiao-ting HU ; Zhi-xian ZHAO ; Qiong-fen LI
Chinese Journal of Disease Control & Prevention 2020;24(2):139-144
Objective To analyze the epidemic trend of hepatitis B virus (HBV) in 18 minority nationalities in Yunnan Province from 2009 to 2018, so as to explore the ethnic differences in the incidence of HBV in Yunnan Province. Methods Based on the reported incidence data of hepatitis B in China's disease prevention and control information system from 2009 to 2018, descriptive epidemiology method was used to describe and analyze the incidence of hepatitis B in different ethnic groups, and K-means clustering method was used to explore and analyze the annual average incidence of hepatitis B in different ethnic groups. Results From 2009 to 2018, the average incidence of hepatitis B in Yunnan Province was 44.26/100 000, which was much lower than the overall level of China every year; the average incidence of hepatitis B in ethnic groups was 41.27/100 000, slightly lower than the overall level of Yunnan every year. The prevalence of hepatitis B was different in different ethnic groups. The average incidence of Wa was significantly higher than others (95.26/100 000), and Jingpo was the lowest (22.51/100 000). According to the incidence of hepatitis B, different ethnic groups were divided into three categories: high incidence ethnic group, middle incidence ethnic group and low incidence ethnic group. Conclusion There are ethnic differences in the incidence of hepatitis B in Yunnan Province. The incidence of hepatitis B in some ethnic groups is higher than that in the whole country all the year round, which is the key population in the prevention and control of hepatitis B.
10.The predictive value and efficacy of the risk model based on the metabolic parameters of 18F-FDG PET-CT for EGFR gene mutations in non-small cell lung cancer
Yang JIANG ; Xiaowei MA ; Chuning DONG ; Zhe XIAO ; Xian LI ; Yunhua WANG
Chinese Journal of Radiology 2020;54(7):688-693
Objective:To explore the value and efficacy of the risk model based on the metabolic parameters of 18F-FDG PET-CT in predicting epidermal growth factor receptor (EGFR) gene mutations in non-small cell lung cancer (NSCLC). Methods:This retrospectives study reviewed 105 NSCLC patients who were tested for EGFR gene expression and underwent 18F-FDG PET-CT exam prior to treatment from Jan 2017 to June 2018 in our hospital. The patients were divided into EGFR mutations group ( n=40) and EGFR wild type group ( n=65). The differences between the different groups were analyzed in several clinical characteristics and three metabolic parameters based on 18F-FDG PET-CT, including the maximal standard uptake value (SUV max), metabolic tumor volume (MTV), total lesion glycolysis (TLG) of the primary tumor. Multivariate logistic regression analysis was performed to identify predictors of EGFR mutations, and the risk prediction model and nomogram graph were constructed. Diagnostic efficiency of the model was done by the receiver operating characteristics (ROC) curve analysis, and the Calibration plot was performed by Hosmer-Lemeshow (H-L) test to evaluate the calibration scale of the model. Results:There were statistically significant differences in gender, smoking status, serum CEA level, length of tumor, pathological types, TTF-1 and NapsinA expression between the EGFR mutant groups and EGFR wild-type groups (all P<0.05). The MTV and TLG of EGFR mutation group were 4.4 (4.5,37.1) cm 3 and 46.6 (21.2,118.2), respectively. The MTV and TLG of EGFR wild type group were 7.4 (3.2,13.5) cm 3 and 95.4 (26.4,345.1), respectively. The MTV and TLG of EGFR mutation group were significantly lower than those of EGFR wild type group ( Z=-2.452, P=0.014; Z=-2.379, P=0.017). ROC curve analysis showed area under the curve (AUC) predicted by SUV max, MTV and TLG for EGFR mutations was 0.597, 0.643 and 0.639, respectively. Multivariate analysis demonstrated that gender, length of tumor, SUV max and MTV were independent predictors of EGFR mutations, with the odds ratio (OR) values (95 %CI) as 3.811 (1.508-9.629), 1.679 (0.899-3.136), 0.928 (0.848-1.015) and 0.924 (0.865-0.986), respectively. The predictive model and nomogram graph was established, with the sensitivity, specificity, positive predictive value, negative predictive value and AUC of 80.0%, 66.2%, 68.8%, 75.3% and 0.775 (0.687-0.864), respectively. The H-L test showed the model had excellent accuracy (χ 2=3.872, P=0.869). Conclusion:The risk model based on the metabolic parameters of 18F-FDG PET-CT has a good performance in predicting the mutations of EGFR gene in patients with NSCLC.

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