1.Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer
Shi QIU ; Yaqi QIU ; Linghui DENG ; Ling NIE ; Liming GE ; Xiaonan ZHENG ; Di JIN ; Kun JIN ; Xianghong ZHOU ; Xingyang SU ; Boyu CAI ; Jiakun LI ; Xiang TU ; Lina GONG ; Liangren LIU ; Zhenhua LIU ; Yige BAO ; Jianzhong AI ; Tianhai LIN ; Lu YANG ; Qiang WEI
Chinese Medical Journal 2024;137(2):209-221
Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.
2.A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020
Cai-Yun WANG ; Hong-Mei XU ; Gang LIU ; Jing LIU ; Hui YU ; Bi-Quan CHEN ; Guo ZHENG ; Min SHU ; Li-Jun DU ; Zhi-Wei XU ; Li-Su HUANG ; Hai-Bo LI ; Dong WANG ; Song-Ting BAI ; Qing-Wen SHAN ; Chun-Hui ZHU ; Jian-Mei TIAN ; Jian-Hua HAO ; Ai-Wei LIN ; Dao-Jiong LIN ; Jin-Zhun WU ; Xin-Hua ZHANG ; Qing CAO ; Zhong-Bin TAO ; Yuan CHEN ; Guo-Long ZHU ; Ping XUE ; Zheng-Zhen TANG ; Xue-Wen SU ; Zheng-Hai QU ; Shi-Yong ZHAO ; Lin PANG ; Hui-Ling DENG ; Sai-Nan SHU ; Ying-Hu CHEN
Chinese Journal of Contemporary Pediatrics 2024;26(2):131-138
Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]
3.Lung Cancer Risk Attributable to Active Smoking in China: A Systematic Review and Meta-Analysis.
Jian ZHAO ; Yu Lin SHI ; Yu Tong WANG ; Fei Ling AI ; Xue Wei WANG ; Wen Yi YANG ; Jing Xin WANG ; Li Mei AI ; Kui Ru HU ; Xia WAN
Biomedical and Environmental Sciences 2023;36(9):850-861
OBJECTIVE:
No consensus exists on the relative risk ( RR) of lung cancer (LC) attributable to active smoking in China. This study aimed to evaluate the unified RR of LC attributable to active smoking among the Chinese population.
METHODS:
A systematic literature search of seven databases was conducted to identify studies reporting active smoking among smokers versus nonsmokers in China. Primary articles on LC providing risk estimates with their 95% confidence intervals ( CIs) for "ever" "former" or "current" smokers from China were selected. Meta-analysis was used to estimate the pooled RR of active smoking.
RESULTS:
Forty-four unique studies were included. Compared with that of nonsmokers, the pooled RR (95% CI) for "ever" "former" and "current" smokers were 3.26 (2.79-3.82), 2.95 (1.71-5.08), and 5.16 (2.58-10.34) among men, 3.18 (2.78-3.63), 2.70 (2.08-3.51), and 4.27 (3.61-5.06) among women, and 2.71 (2.12-3.46), 2.66 (2.45-2.88), and 4.21 (3.25-5.45) in both sexes combined, respectively.
CONCLUSION
The RR of LC has remained relatively stable (range, 2-6) over the past four decades in China. Early quitting of smoking could reduce the RR to some extent; however, completely refraining from smoking is the best way to avoid its adverse effects.
Male
;
Humans
;
Female
;
Smoking/epidemiology*
;
Smoking Cessation
;
Smokers
;
Risk
;
Lung Neoplasms/etiology*
;
Risk Factors
4.Cerebral toxoplasmosis after hematopoietic stem cell transplantation in two children with thalassemia.
Qun Qian NING ; Wen Qiang XIE ; Qiao Chuan LI ; Lian Jin LIU ; Zhong Ming ZHANG ; Ling Ling SHI ; Mei Qing WU ; Zw Yan SHI ; Zhong Qing LI ; Yong Rong LAI ; Mu Liang JIANG ; Mei Ai LIAO ; Rong Rong LIU
Chinese Journal of Pediatrics 2023;61(3):271-273
5.The Association between Exposure to Second-Hand Smoke and Disease in the Chinese Population: A Systematic Review and Meta-Analysis.
Yu Tong WANG ; Kui Ru HU ; Jian ZHAO ; Fei Ling AI ; Yu Lin SHI ; Xue Wei WANG ; Wen Yi YANG ; Jing Xin WANG ; Li Mei AI ; Xia WAN
Biomedical and Environmental Sciences 2023;36(1):24-37
OBJECTIVE:
To analyze the association between exposure to second-hand smoke (SHS) and 23 diseases, categorized into four classifications, among the Chinese population.
METHODS:
We searched the literature up to June 30, 2021, and eligible studies were identified according to the PECOS format: Participants and Competitors (Chinese population), Exposure (SHS), Outcomes (Disease or Death), and Study design (Case-control or Cohort).
RESULTS:
In total, 53 studies were selected. The odds ratio (OR) for all types of cancer was 1.79 (1.56-2.05), and for individual cancers was 1.92 (1.42-2.59) for lung cancer, 1.57 (1.40-1.76) for breast cancer, 1.52 (1.12-2.05) for bladder cancer, and 1.37 (1.08-1.73) for liver cancer. The OR for circulatory system diseases was 1.92 (1.29-2.85), with a value of 2.29 (1.26-4.159) for stroke. The OR of respiratory system diseases was 1.76 (1.13-2.74), with a value of 1.82 (1.07-3.11) for childhood asthma. The original ORs were also shown for other diseases. Subgroup analyses were performed for lung and breast cancer. The ORs varied according to time period and were significant during exposure in the household; For lung cancer, the OR was significant in women.
CONCLUSION
The effect of SHS exposure in China was similar to that in Western countries, but its definition and characterization require further clarification. Studies on the association between SHS exposure and certain diseases with high incidence rates are insufficient.
Child
;
Female
;
Humans
;
Asthma/epidemiology*
;
Breast Neoplasms
;
East Asian People
;
Lung Neoplasms/etiology*
;
Tobacco Smoke Pollution/adverse effects*
;
China
6.Guideline for clinical comprehensive evaluation of Chinese patent medicine (2022 version).
Wei-An YUAN ; Jun-Hua ZHANG ; Jian-Ping LIU ; Zhong-Qi YANG ; Jun-Ling CAO ; Xing LIAO ; Xiao-Yu XI ; Mei HAN ; Wen-Yuan LI ; Zhen-Wen QIU ; Shi-Yin FENG ; Yuan-Yuan GUO ; Lu-Jia CAO ; Xiao-Hong LIAO ; Yan-Ling AI ; Ju HUANG ; Lu-Lu JIA ; Xiang-Fei SU ; Xue WU ; Ze-Qi DAI ; Ji-Hua GUO ; Bing-Qing LU ; Xiao-Xiao ZHANG ; Jian-Yuan TANG
China Journal of Chinese Materia Medica 2023;48(1):256-264
Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.
Medicine, Chinese Traditional
;
Nonprescription Drugs
;
Consensus
;
China
;
Reference Standards
;
Drugs, Chinese Herbal
7. Betulinic Acid Improves Cardiac Function in Septic Rats Through AKT / mTOR and AKT / AMPK -modulated Autophagy
Xiang-Fei MENG ; Xin-Ru ZHOU ; Jing HUANG ; Meng-Yuan CHEN ; Li-Juan LIU ; Lu-Jia SHI ; Ci-Ai CHEN ; Ling-Bo QIAN
Chinese Journal of Biochemistry and Molecular Biology 2023;39(6):840-847
Betulinic acid (BA) exerts protective effects on organs in septic animals. However, whether BA can improve cardiac function in sepsis and the underlying mechanism remain unclear. Here, male Sprague-Dawley rats were pretreated with BA (25 mg/ kg/ d, i. g.) for 5 days and then intraperitoneally injected with lipopolysaccharide (LPS, 10 mg/ kg). The rats were anesthetized to determine transthoracic echocardiography using a high-resolution imaging system for small animals after they were treated with LPS for 6 h. Histopathologic alterations were examined by HE staining. Myocardial injury markers (cTnI and CK-MB) and inflammatory factors (TNF-α, IL-1β and IL-6) in the serum were measured by the enzyme-linked immunosorbent assay. Autophagy-related proteins (p62 and LC3 Ⅱ) and AKT-modulated autophagy pathways in the myocardium were determined by Western blotting. Pretreatment with BA markedly improved left ventricular ejection fraction (EF) and fraction shortening (FS) (P<0. 05), improved myocardial histomorphology, and significantly inhibited cTnI, CK-MB, TNF-α, IL-1β and IL-6 (P<0. 05) in the septic rat serum. BA markedly decreased p62 (P<0. 01), increased LC3 Ⅱ (P< 0. 001), and significantly down-regulated p-AKT (Thr308), p-AMPKα (Ser485/ 491), p-mTOR (Ser2448) and p-S6K (Thr389) (P<0. 05), while markedly up-regulated p-AMPKα (Thr172) and pULK1 (Ser317) (P<0. 01) in septic rat hearts. The findings indicate that BA can attenuate sepsis-induced myocardial dysfunctions associated with down-regulating autophagy inhibiting pathways mediated by AKT/ mTOR and AKT/ AMPK pathways.
8.Evaluating the Quality of Case-control Studies involving the Association between Tobacco Exposure and Diseases in a Chinese Population based on the Newcastle-Ottawa Scale and Post-hoc Power.
Yu Lin SHI ; Jian ZHAO ; Fei Ling AI ; Yu Tong WANG ; Kui Ru HU ; Xue Wei WANG ; Wen Yi YANG ; Jing Xin WANG ; Li Mei AI ; Xia WAN
Biomedical and Environmental Sciences 2022;35(9):861-866
9.Analysis on occupational noise deafness in a provincial occupational disease diagnosis institution from 2016 to 2020
YU Xin yang HU Shi jie ZHENG Qian ling YANG Ai chu LI Bin
China Occupational Medicine 2022;49(05):558-
Objective - ( )
To analyze the epidemiological characteristics of occupational noise induced deafness ONID
( )
diagnosed by Guangdong Province Hospital of Occupational Disease Prevention and Control GDHOD from 2016 to 2020 and
- Methods
the reasons non ONID diagnosis. The data of ONID patients diagnosed in GDHOD from 2016 to 2020 were collected
“
from the Occupational Disease Report Card in the Occupational Disease and Occupational Health Information Monitoring
” “ ” -
System subsystem of the China Disease Prevention and Control Information System . The data of non ONID subjects were
,
collected from the occupational disease diagnosis archives in the same hospital and the relevant data were analyzed
Results , , ( )
retrospectively. Of the 1 432 subjects 824 subjects were diagnosed as ONID patients mainly of mild ONID 86.0% .
(M) , M
Male patients accounted for 88.0%. The median of diagnosis age was 45.0 years old and of length of employment of
, , ,
diagnosis was 8.3 years. ONID patients were mainly found in Zhongshan Dongguan Zhuhai Jiangmen and Guangzhou City in
, , ( )
the Pearl River Delta accounting for 67.6%. The cases distributed in 519 enterprises mainly on manufacturing 90.2% .
, - , ;
Among the 139 enterprises each enterprise had 2 11 patients worked within five years accounting for 53.9% 91.1% of the
-, - - -
ONID patients were distributed in large medium and small enterprises. ONID patients mainly worked in non public
enterprises that accounted for 91.3%. There were 606 subjects could not be diagnosed as ONID. The main reasons for not being
( ),
diagnosed were that the weighted value of better ear hearing threshold was less than 26 dB 34.8% the working history of
( ),
occupational noise exposure was less than three years 31.5% the weighted value of better ear hearing threshold was less thanConclusion
26 dB and the average hearing threshold of binaural high frequency was less than 40 dB 16.2% . The ONID
, , -, -
patients have the characteristics of group aggregation. The Pearl River Delta manufacturing industry large medium and
- - :
small non public enterprises are the key points of ONID prevention. The main reasons for not being diagnosed as ONID were
,
the working history of occupational noise exposure was less than three years the weighted value of better ear hearing threshold
, -
was less than 26 dB and the average high frequency hearing threshold of both ears was less than 40 dB.
10.Effect of Ethyl Acetate Extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis on Intestinal Flora in ApoE-/- Mice with Atherosclerosis
Ai-ling JIA ; Yu-hang ZHANG ; Yuan-yuan DIAO ; Yu-wen SHI ; Meng-cheng JIANG ; Jun-ge LI ; Ye QIU ; Zhi-dong QIU ; Chao-mei FU
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(5):108-115
ObjectiveTo observe the effect of ethyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis on high-fat diet-induced apolipoprotein E gene knockout (ApoE-/-) mice, and explore its mechanism of treating atherosclerosis by regulating intestinal flora. MethodThirty-two 8-week-old male ApoE-/- mice were randomly divided into model group, rosuvastatin group (10 mg·kg-1), high-, low-dose groups of ethyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis (75, 25 mg·kg-1), with 8 mice in each group. Eight C57BL/6 mice were used as blank group. After 8 weeks of continuous administration, blood was taken to determine the blood lipid level. Enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of related indexes in serum of mice. Hematoxylin-eosin (HE) staining was used to observe the formation of aortic plaque in mice. Cecal contents were collected and 16S rRNA amplicon sequencing was used to detect intestinal flora. ResultCompared with the blank group, the plaque area of the model group was significantly increased with inflammatory infiltration, the contents of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), inflammatory factors and inducible nitric oxide synthase (iNOS) were increased, while the content of high-density lipoprotein cholesterol (HDL-C) was decreased. Compared with the model group, rosuvastatin group and high- and low-dose groups of ethyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis could improve the deposition of aortic plaque, reduce the contents of TG, TC, LDL-C, inflammatory factors and iNOS, and increase the content of HDL-C. Compared with the blank group, the relative abundances of Firmicutes and Proteobacteria in the model group increased, while the relative abundance of Bacteroidetes decreased. Alpha and Beta diversity analysis showed that samples of each group could be significantly isolated, and the total number and abundance of intestinal flora species in the model group were low. Compared with the model group, ethyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis could increase the relative abundance of beneficial bacteria and decrease the relative abundance of pathogenic bacteria. ConclusionEthyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis was mainly composed of flavonoids, which can treat atherosclerosis by regulating the intestinal flora and improve the pathological changes in the aorta of ApoE-/- mice induced by high-fat diet. The mechanism may be related to its ability to reduce the level of inflammatory factors, improve antioxidant capacity and repair the disorder of intestinal flora structure.

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