1.Celastrol directly targets LRP1 to inhibit fibroblast-macrophage crosstalk and ameliorates psoriasis progression.
Yuyu ZHU ; Lixin ZHAO ; Wei YAN ; Hongyue MA ; Wanjun ZHAO ; Jiao QU ; Wei ZHENG ; Chenyang ZHANG ; Haojie DU ; Meng YU ; Ning WAN ; Hui YE ; Yicheng XIE ; Bowen KE ; Qiang XU ; Haiyan SUN ; Yang SUN ; Zijun OUYANG
Acta Pharmaceutica Sinica B 2025;15(2):876-891
Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.
2.Analysis of AHFtest-based HIV antibody self-testing data
ZHENG Jinlei ; HE Lin ; WANG Hui ; CHEN Wanjun ; JIANG Tingting ; CHEN Weiyong ; CHEN Lin
Journal of Preventive Medicine 2024;36(2):156-158
Objective:
To investigate the characteristics of AHFtest-based HIV antibody self-testing among male adolescents at ages of 15 to 24 years, so as to provide insights into the promotion of HIV antibody self-testing.
Methods:
Data were collected from male adolescents at ages of 15 to 24 years that applied for HIV antibody self-testing in the AHFtest platform from 2019 to 2021, with mailing address showing as Zhejiang Province, and demographics, applying cause and testing results were analyzed.
Results:
A total of 268 male adolescents were enrolled, with a median age of 22.00 (interquartile range, 3.00) years. There were 160 cases with an educational level of junior college/bachelor (59.70%), 147 students (54.85%), 175 men who had sex with men (65.30%), and 126 cases with a history of previous HIV antibody self-testing (47.01%). The main causes for applying for HIV antibody self-testing through AHFtest were "easy to operate" (259 cases, 96.64%) and "privacy protect" (102 cases, 38.06%). There were 203 subjects that applied once HIV antibody self-testing (75.75%), and 65 subjects that applied multiple self-testing (24.25%). There were 123 subjects that uploaded their test results (45.90%), including 3 cases with HIV antibody positive, and 125 subjects that did not tell others the self-testing results (46.64%).
Conclusions
Among male applicants at ages of 15 to 24 years in Zhejiang Province from 2019 to 2021, students are predominant occupation. Easy to operate and privacy protect are the main cause for the application, but the proportion of detection results uploading is relatively low.
3.Tenecteplase versus alteplase in treatment of acute ST-segment elevation myocardial infarction: A randomized non-inferiority trial
Xingshan ZHAO ; Yidan ZHU ; Zheng ZHANG ; Guizhou TAO ; Haiyan XU ; Guanchang CHENG ; Wen GAO ; Liping MA ; Liping QI ; Xiaoyan YAN ; Haibo WANG ; Qingde XIA ; Yuwang YANG ; Wanke LI ; Juwen RONG ; Limei WANG ; Yutian DING ; Qiang GUO ; Wanjun DANG ; Chen YAO ; Qin YANG ; Runlin GAO ; Yangfeng WU ; Shubin QIAO
Chinese Medical Journal 2024;137(3):312-319
Background::A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.Methods::In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.Results::From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. Conclusion::rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.Trial registration::www.ClinicalTrials.gov (No. NCT02835534).
4.Diagnosis, treatment and prevention of severe acute respiratory syndrome coronavirus 2 infection in children: experts′ consensus statement (Fifth Edition)updated for the Omicron variant
Rongmeng JIANG ; Zhengde XIE ; Yi JIANG ; Xiaoxia LU ; Runming JIN ; Yuejie ZHENG ; Yunxiao SHANG ; Baoping XU ; Zhisheng LIU ; Gen LU ; Jikui DENG ; Guanghua LIU ; Xiaochuan WANG ; Jianshe WANG ; Luzhao FENG ; Wei LIU ; Yi ZHENG ; Sainan SHU ; Min LU ; Wanjun LUO ; Miao LIU ; Yuxia CUI ; Leping YE ; Adong SHEN ; Gang LIU ; Liwei GAO ; Lijuan XIONG ; Yan BAI ; Likai LIN ; Zhuang WEI ; Fengxia XUE ; Tianyou WANG ; Dongchi ZHAO ; Zhengyan ZHAO ; Jianbo SHAO ; Wong Wing-kin GARY ; Yanxia HE ; Xingwang LI ; Yonghong YANG ; Kunling SHEN
Chinese Journal of Applied Clinical Pediatrics 2023;38(1):20-30
China has classified the Corona Virus Disease 2019(COVID-19) as a statutory category B infectious disease and managed it according to Category B since January 8, 2023.In view that Omicron variant is currently the main epidemic strain in China, in order to guide the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection in children with the times, refer to the Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial 10 th Edition), Expert Consensus on Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fourth Edition) and the Diagnosis and Treatment Strategy for Pediatric Related Viral Infections.The Expert Consensus on the Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fifth Edition) has been formulated and updated accordingly on related etiology, epidemiology, pathogenic mechanism, clinical manifestations, auxiliary examination, diagnosis and treatment, and added key points for the treatment of COVID-19 related encephalopathy, fulminating myocarditis and other serious complications for clinical reference.
5.Specific Regulation of m6A by SRSF7 Promotes the Progression of Glioblastoma.
Yixian CUN ; Sanqi AN ; Haiqing ZHENG ; Jing LAN ; Wenfang CHEN ; Wanjun LUO ; Chengguo YAO ; Xincheng LI ; Xiang HUANG ; Xiang SUN ; Zehong WU ; Yameng HU ; Ziwen LI ; Shuxia ZHANG ; Geyan WU ; Meisongzhu YANG ; Miaoling TANG ; Ruyuan YU ; Xinyi LIAO ; Guicheng GAO ; Wei ZHAO ; Jinkai WANG ; Jun LI
Genomics, Proteomics & Bioinformatics 2023;21(4):707-728
Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N6-methyladenosine (m6A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m6A methylation. We then indicate that SRSF7 is a novel m6A regulator, which specifically facilitates the m6A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m6A methyltransferase. The two m6A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m6A and validates the presence and functional importance of temporal- and spatial-specific regulation of m6A mediated by RNA-binding proteins (RBPs).
Humans
;
Cell Line, Tumor
;
Cell Proliferation
;
Gene Expression Regulation, Neoplastic
;
Glioblastoma/genetics*
;
Methyltransferases/metabolism*
;
RNA Splicing Factors/metabolism*
;
RNA, Messenger/genetics*
;
RNA-Binding Proteins/metabolism*
;
Serine-Arginine Splicing Factors/metabolism*
;
RNA Methylation/genetics*
6.Factors affecting HIV testing among male college students with sexual behaviors
Hui WANG ; Xiaohong PAN ; Qiaoqin MA ; Weiyong CHEN ; Lin HE ; Jinlei ZHENG ; Wanjun CHEN ; Tingting JIANG
Journal of Preventive Medicine 2022;34(11):1081-1085
Objective:
To investigate the factors affecting HIV testing among male college students with sexual behaviors, so as to provide the evidence for improving the detection of HIV testing among young college students.
Methods:
Four undergraduate universities and one junior college were randomly sampled from Hangzhou City using a purposive sampling method during the period between September and November, 2021, and male students with self-reported sexual behaviors were recruited as study students. Participants' demographics, AIDS-related knowledge, sexual behaviors and HIV testing were collected using questionnaires, and factors affecting HIV testing using a multivariable logistic regression model.
Results:
A total of 720 male college students with sexual behaviors were enrolled, including 180 freshmen (25.00%), 178 sophomores (24.72%), 163 juniors (22.64%), 50 seniors (6.94%) and 149 postgraduates (20.69%), and 94 students received HIV testing (13.06%), including 57.45% receiving self-testing. Multivariable logistic regression analysis identified postgraduates (OR=0.302, 95%CI: 0.127-0.719), sexual orientation (homosexual, OR=0.090, 95%CI: 0.028-0.294; bisexual/uncertain, OR=0.181, 95%CI: 0.066-0.495), awareness of HIV testing (low awareness, OR=0.411, 95%CI: 0.176-0.957; moderate awareness, OR=0.305, 95%CI: 0.123-0.757; high awareness, OR=0.087, 95%CI: 0.032-0.235) as factors affecting HIV testing among male college students with sexual behaviors.
Conclusions
The prevalence of HIV testing correlates with awareness of HIV testing among male college students with sexual behaviors. Improvements in health education of HIV testing and accessibility of HIV testing services are recommended.
7.Characteristics of male college students with temporary heterosexual behaviors through Internet dating
Wanjun CHEN ; Lin CHEN ; Hui WANG ; Lin HE ; Weiyong CHEN ; Tingting JIANG ; Jinlei ZHENG ; Xiaohong PAN ; Qiaoqin MA
Journal of Preventive Medicine 2022;34(11):1086-1090
Objective:
To investigate the characteristics of temporary heterosexual behaviors among male college students through Internet dating, so as to provide insights into HIV/AIDS control among young college students.
Methods:
A total of 15 universities/colleges were sampled from Zhejiang Province using a stratified cluster sampling method, and 3 schools/departments were sampled from each university/college. Male college students with temporary heterosexual behaviors during the past year were recruited. Participants' demographics, AIDS-related knowledge, compliance to HIV/AIDS interventions, Internet dating and sexual behaviors were collected, and the characteristics of male college students with Internet dating were analyzed.
Results :
A total of 326 students were enrolled, including 202 participants from regular institutions of higher education (61.96%) and 124 students from higher vocational colleges (38.04%). There were 79 freshmen (24.23%), 99 sophomores (30.37%), 104 juniors (31.90%) and 44 seniors (13.50%), and there were 100 participants (30.67%) with temporary heterosexual behaviors through Internet dating during the past year. Among the 100 participants, there were 75.00% of participants knowing “man who have sex with man is the main transmission pattern of AIDS among young students in China”, 93.00% knowing “insisting on accurate use of condoms may reduce the risk of HIV infections and transmission” and 93.00% knowing “seeking HIV testing and counseling actively following high-risk behaviors”. There were 77 participants (77.00%) with students as their temporary heterosexual partners, 17 participants (17.00%) that had received HIV self-testing and 17 participants (17.00%) that had received HIV testing in medical institutions, 22 participants (22.00%) that had never used condoms during temporary heterosexual behaviors during the past year, and 29 participants (29.00%) with commercial sexual behaviors during the past year. In addition, male college students with temporary heterosexual behaviors through Internet dating were more unlikely to use condoms and more likely to have commercial sexual behaviors than those with dating through other ways (P<0.05).
Conclusions
Male college students with temporary heterosexual behaviors through Internet dating are more likely to have high-risk sexual behaviors than those with dating through other ways. Internet-based mobile sexual education and HIV/AIDS health education are recommended.
8.Factors affecting multiple sexual partner behaviors among men who have sex with men at ages of 16 to 24 years in Zhejiang Province
Tingting JIANG ; Qiaoqin MA ; Lin CHEN ; Lin HE ; Wanjun CHEN ; Weiyong CHEN ; Hui WANG ; Jinlei ZHENG
Journal of Preventive Medicine 2022;34(11):1091-1095
Objective :
To investigate the factors affecting multiple sexual partner behaviors among men who have sex with men (MSM) at ages of 16 to 24 years in Zhejiang Province, so as to provide the evidence for formulating the integrated interventions for HIV/AIDS among adolescents.
Methods :
The demographic features, sexual behaviors and HIV testing were collected from MSM at ages of 16 to 24 years in Zhejiang Province through the Management Information System of China AIDS Fund for Non-governmental Organizations (CAFNGO) in 2021. The factors affecting multiple sexual partner behaviors were identified among MSM at ages of 16 to 24 years using a multivariable logistic regression model.
Results :
A total of 1 253 participants were enrolled, with a mean age of (21.16±2.06) years. There were 1 219 unmarried respondents (97.29%), 807 (64.61%) with diploma and above, 250 (19.95%) with multiple sexual partners during the past 3 months, 344 (27.45%) with unprotected sexual behaviors in the past 3 months, 71 (5.67%) that had used rush or new drugs, 511 (40.78%) that were unaware of their sexual partners' HIV infections, 28 (2.23%) with symptoms or diagnosis of sexually transmitted diseases, and 35 (2.79%) with positive HIV testing. Multivariable logistic regression analysis identified age (19 years-, OR=2.563, 95%CI: 1.404-4.679; 22 to 24 years, OR=2.149, 95%CI: 1.180-3.913), having unprotected sexual behaviors in the past 3 months (OR=5.338, 95%CI: 3.938-7.237), having used rush or new drugs in the past 3 months (OR=3.669, 95%CI: 2.142-6.286), unaware of sexual partners' HIV infections(OR=1.402, 95%CI: 1.032-1.903), and positive HIV tests (OR=2.763, 95%CI: 1.298-5.880) as factors affecting multiple sexual behaviors among MSM at ages of 16 to 24 years.
Conclusions
The multiple sexual behaviors correlate with age, unprotected sexual behaviors, use of rush or new drugs and unawareness of sexual partners' HIV infections among MSM at ages of 16 to 24 years.
9.Effects of botulinum toxin A injection therapy with ultrasound-guided for benign masseter hypertrophy
Qin YANG ; Xueyong LI ; Yuejun LI ; Tao LIU ; Pan REN ; Wenwen KANG ; Wanjun ZHENG ; Congying ZHAO
Chinese Journal of Medical Aesthetics and Cosmetology 2022;28(5):409-412
Objective:To evaluate the efficacy of botulinum toxin A injection therapy with ultrasound-guided for benign masseter hypertrophy.Methods:Twenty cases (40 sides) of masseter hypertrophy were injected with botulinum toxin A, among which 10 cases were taken as experimental group and the other 10 cases as control group. The experimental group had preoperative ultrasound examination to measure the thickness of masseter, and use ultrasound-guided precise injection during the operation, and then ultrasound recheck to measure the postoperative masseter thickness; The other 10 cases of control group adopt traditional 3-point injection method.Results:The masseter thickness of the two groups at different period of times after treatment was decreased ( P<0.001), the most obviously decrease happened 4-12 weeks after injection. The mean reduction was 26.8% at 4 weeks and 28.4% at 12 weeks after injection. Masseter muscle thickness recovered by 22% at 24 weeks and by 20% at 36 weeks. The average follow-up was 6.0±2.4 months with no serious complications occurred. In the control group, there was a partial masseter bulge in one case. The satisfactory rate of the patients in the experimental group was higher than that of the control group. Conclusions:Botulinum toxin A injection therapy with ultrasound-guided for benign masseter hypertrophy is an effective treatment, which is more accurate and effective than the traditional injection method.
10.Expert consensus on the diagnosis, treatment and prevention of monkeypox in children
Rongmeng JIANG ; Yuejie ZHENG ; Lei ZHOU ; Luzhao FENG ; Lin MA ; Baoping XU ; Hongmei XU ; Wei LIU ; Zhengde XIE ; Jikui DENG ; Lijuan XIONG ; Wanjun LUO ; Zhisheng LIU ; Sainan SHU ; Jianshe WANG ; Yi JIANG ; Yunxiao SHANG ; Miao LIU ; Liwei GAO ; Zhuang WEI ; Guanghua LIU ; Gang LIU ; Wei XIANG ; Yuxia CUI ; Gen LU ; Min LU ; Xiaoxia LU ; Runming JIN ; Yan BAI ; Leping YE ; Dongchi ZHAO ; Adong SHEN ; Xiang MA ; Qinghua LU ; Fengxia XUE ; Jianbo SHAO ; Tianyou WANG ; Zhengyan ZHAO ; Xingwang LI ; Yonghong YANG ; Kunling SHEN
Chinese Journal of Applied Clinical Pediatrics 2022;37(13):964-973
Monkeypox is a zoonotic disease.Previous studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications.In order to improve pediatricians′ understanding of monkeypox and achieve early detection, early diagnosis, early treatment and early disposal, the committee composed of more than 40 experts in the related fields of infectious diseases, pediatrics, infection control and public health formulate this expert consensus, on the basis of the latest clinical management and infection prevention and control for monkeypox released by the World Health Organization (WHO), the guidelines for diagnosis and treatment of monkeypox (version 2022) issued by National Health Commission of the People′s Republic of China and other relevant documents.During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis and differential diagnosis, treatment, discharge criteria, prevention, case management process and key points of prevention and control about monkeypox.


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