1.Trilogy of drug repurposing for developing cancer and chemotherapy-induced heart failure co-therapy agent.
Xin CHEN ; Xianggang MU ; Lele DING ; Xi WANG ; Fei MAO ; Jinlian WEI ; Qian LIU ; Yixiang XU ; Shuaishuai NI ; Lijun JIA ; Jian LI
Acta Pharmaceutica Sinica B 2024;14(2):729-750
Chemotherapy-induced complications, particularly lethal cardiovascular diseases, pose significant challenges for cancer survivors. The intertwined adverse effects, brought by cancer and its complication, further complicate anticancer therapy and lead to diminished clinical outcomes. Simple supplementation of cardioprotective agents falls short in addressing these challenges. Developing bi-functional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events simultaneously. Drug repurposing was naturally endowed with co-therapeutic potential of two indications, implying a unique chance in the development of bi-functional agents. Herein, we further proposed a novel "trilogy of drug repurposing" strategy that comprises function-based, target-focused, and scaffold-driven repurposing approaches, aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional agent. Through function-based repurposing, a cardioprotective agent, carvedilol (CAR), was identified as a potential neddylation inhibitor to suppress lung cancer growth. Employing target-focused SAR studies and scaffold-driven drug design, we synthesized 44 CAR derivatives to achieve a balance between anticancer and cardioprotection. Remarkably, optimal derivative 43 displayed promising bi-functional effects, especially in various self-established heart failure mice models with and without tumor-bearing. Collectively, the present study validated the practicability of the "trilogy of drug repurposing" strategy in the development of bi-functional co-therapy agents.
2.Comparison of clinical efficacy of NOSES combined with ERAS and conventional laparoscopic surgery in treatment of rectal cancer
Feng SONG ; Feng GAO ; Ming XU ; Jian GAO ; Zeng-Xi MAO
Medical Journal of Chinese People's Liberation Army 2024;49(1):31-36
Objective To compare the clinical efficacy of natural orifice specimen extraction surgery(NOSES)combined with enhanced recovery after surgery(ERAS)and conventional laparoscopic surgery in treatment of rectal cancer patients.Methods A hundred patients with rectal cancer in the Department of Colorectal and Anal Surgery,the 940th Hospital of Joint Logistics Support Force of PLA were selected as the research objects from January 2019 to December 2021,including 49 cases treated with NOSES combined with ERAS were set as the observation group,and 51 cases treated with conventional laparoscopic surgery of rectal cancer were set as the control group.Postoperative C-reactive protein(CRP),procalcitonin(PCT),interleukin-6(IL-6),white blood cell count(WBC),percentage of neutrophil(NEUT),K+ concentration,postoperative peristalsis recovery time,first time out-of-bed activity,first liquid feeding time,removal time of urinary,and drainage tubes,hospital stay and intraoperative blood loss,number of lymph node detection,positive margin rate,incidence of complications,and pain score were compared between the two groups.Results The observation group showed significant lower postoperative CRP,PCT,IL-6 levels when compared with control group(P<0.05),while no significant difference in K+ concentration between the two groups(P>0.05).The recovery time of intestinal peristalsis,the time of the first out-of-bed activity,the first liquid feeding time,the time of removal of the urinary tube and the drainage tube,and the number of days of hospitalization in observation group were all superior to the control group(P<0.05).The observation group with the duration of surgery was longer than the control group,and the difference was statistically significant(P<0.05).There were no significant differences in intraoperative bleeding,number of lymph nodes detected and positive rate of resection margins between the two groups(P>0.05).There was no significant difference in the incidence of complications between the two groups(4.1%vs.7.8%,P>0.05).The observation group showed significant lower pain scores than control group on the 1st,2nd and 3rd day after surgery(P<0.05).Conclusions NOSES combined with ERAS in treatment of rectal cancer patients is safe and feasible,can narrow the surgical incision,alleviate stress response and postoperative pain,improve postoperative efficacy and reduce the occurrence of complications,so is worthy of promotion and application.
3.Inferring Mycobacterium Tuberculosis Drug Resistance and Transmission using Whole-genome Sequencing in a High TB-burden Setting in China
Feng Yu FAN ; Xin Dong LIU ; Wang Yi CHEN ; Chao Xi OU ; Zhi Qi MAO ; Ting Ting YANG ; Jiang Xi WANG ; Cong Wen HE ; Bing ZHAO ; Jiang Zhen LIU ; Maiweilanjiang ABULIMITI ; Maimaitiaili AIHEMUTI ; Qian GAO ; Lin Yan ZHAO
Biomedical and Environmental Sciences 2024;37(2):157-169
Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking. Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns. Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023-1.954;P = 0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains. Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.
4.Iodine Nutrition,Thyroid-stimulating Hormone,and Related Factors of Postpartum Women from three Different Areas in China:A Cross-sectional Survey
Yun Xiao SHAN ; Yan ZOU ; Chun Li HUANG ; Shan JIANG ; Wen Wei ZHOU ; Lan Qiu QIN ; Qing Chang LIU ; Yan Xiao LUO ; Xi Jia LU ; Qian De MAO ; Min LI ; Yu Zhen YANG ; Chen Li YANG
Biomedical and Environmental Sciences 2024;37(3):254-265
Objective Studies on the relationship between iodine,vitamin A(VA),and vitamin D(VD)and thyroid function are limited.This study aimed to analyze iodine and thyroid-stimulating hormone(TSH)status and their possible relationships with VA,VD,and other factors in postpartum women. Methods A total of 1,311 mothers(896 lactating and 415 non-lactating)from Hebei,Zhejiang,and Guangxi provinces were included in this study.The urinary iodine concentration(UIC),TSH,VA,and VD were measured. Results The median UIC of total and lactating participants were 142.00 μg/L and 139.95 μg/L,respectively.The median TSH,VA,and VD levels in all the participants were 1.89 mIU/L,0.44 μg/mL,and 24.04 ng/mL,respectively.No differences in the UIC were found between lactating and non-lactating mothers.UIC and TSH levels were significantly different among the three provinces.The rural UIC was higher than the urban UIC.Obese mothers had a higher UIC and a higher prevalence of excessive TSH.Higher UICs and TSHs levels were observed in both the VD deficiency and insufficiency groups than in the VD-sufficient group.After adjustment,no linear correlation was observed between UIC and VA/VD.No interaction was found between vitamins A/D and UIC on TSH levels. Conclusion The mothers in the present study had no iodine deficiency.Region,area type,BMI,and VD may be related to the iodine status or TSH levels.
5.Advances in mesenchymal stem cells therapy for tendinopathies
Xu-Feng MAO ; Xi-Qian ZHANG ; Zhe-Yu YAO ; Hai-Jiao MAO
Chinese Journal of Traumatology 2024;27(1):11-17
Tendinopathies are chronic diseases of an unknown etiology and associated with inflammation. Mesenchymal stem cells (MSCs) have emerged as a viable therapeutic option to combat the pathological progression of tendinopathies, not only because of their potential for multidirectional differentiation and self-renewal, but also their excellent immunomodulatory properties. The immunomodulatory effects of MSCs are increasingly being recognized as playing a crucial role in the treatment of tendinopathies, with MSCs being pivotal in regulating the inflammatory microenvironment by modulating the immune response, ultimately contributing to improved tissue repair. This review will discuss the current knowledge regarding the application of MSCs in tendinopathy treatments through the modulation of the immune response.
6.Hepatitis C virus infection:surveillance report from China Healthcare-as-sociated Infection Surveillance System in 2020
Xi-Mao WEN ; Nan REN ; Fu-Qin LI ; Rong ZHAN ; Xu FANG ; Qing-Lan MENG ; Huai YANG ; Wei-Guang LI ; Ding LIU ; Feng-Ling GUO ; Shu-Ming XIANYU ; Xiao-Quan LAI ; Chong-Jie PANG ; Xun HUANG ; An-Hua WU
Chinese Journal of Infection Control 2024;23(1):1-8
Objective To investigate the infection status and changing trend of hepatitis C virus(HCV)infection in hospitalized patients in medical institutions,and provide reference for formulating HCV infection prevention and control strategies.Methods HCV infection surveillance results from cross-sectional survey data reported to China Healthcare-associated Infection(HAI)Surveillance System in 2020 were summarized and analyzed,HCV positive was serum anti-HCV positive or HCV RNA positive,survey result was compared with the survey results from 2003.Results In 2020,1 071 368 inpatients in 1 573 hospitals were surveyed,738 535 of whom underwent HCV test,4 014 patients were infected with HCV,with a detection rate of 68.93%and a HCV positive rate of 0.54%.The positive rate of HCV in male and female patients were 0.60%and 0.48%,respectively,with a statistically sig-nificant difference(x2=47.18,P<0.001).The HCV positive rate in the 50-<60 age group was the highest(0.76%),followed by the 40-<50 age group(0.71%).Difference among all age groups was statistically signifi-cant(x2=696.74,P<0.001).In 2003,91 113 inpatients were surveyed.35 145 of whom underwent HCV test,resulting in a detection rate of 38.57%;775 patients were infected with HCV,with a positive rate of 2.21%.In 2020,HCV positive rates in hospitals of different scales were 0.46%-0.63%,with the highest in hospital with bed numbers ranging 600-899.Patients'HCV positive rates in hospitals of different scales was statistically signifi-cant(X2=35.34,P<0.001).In 2020,12 provinces/municipalities had over 10 000 patients underwent HCV-rela-ted test,and HCV positive rates ranged 0.19%-0.81%,with the highest rate from Hainan Province.HCV posi-tive rates in different departments were 0.06%-0.82%,with the lowest positive rate in the department of pedia-trics and the highest in the department of internal medicine.In 2003 and 2020,HCV positive rates in the depart-ment of infectious diseases were the highest,being 7.95%and 3.48%,respectively.Followed by departments of orthopedics(7.72%),gastroenterology(3.77%),nephrology(3.57%)and general intensive care unit(ICU,3.10%)in 2003,as well as departments of gastroenterology(1.35%),nephrology(1.18%),endocrinology(0.91%),and general intensive care unit(ICU,0.79%)in 2020.Conclusion Compared with 2003,HCV positive rate decreased significantly in 2020.HCV infected patients were mainly from the department of infectious diseases,followed by departments of gastroenterology,nephrology and general ICU.HCV infection positive rate varies with gender,age,and region.
7.Study on Chemical Constituents in Thamnolia Subuliformis (Ehrh.) W.Culb. by UHPLC-Q-Exactive Focus-MS/MS
Shasha LI ; Zhibiao DI ; Jing HU ; Yajuan LI ; Ajuan MAO ; Fan LI ; Fang LI ; Hong ZHANG ; Weifeng WANG
Chinese Journal of Modern Applied Pharmacy 2024;41(1):71-79
OBJECTIVE
To conduct a rapid qualitative study on the chemical constituents of the methanol extract in Thamnolia subuliformis (Ehrh.) W.Culb. by UHPLC-Q-Exactive Focus-MS/MS.
METHODS
The chromatographic separation was performed on a Waters Acquity UPLC BEH C18(2.1 mm×50 mm, 1.7 μm) column with acetonitrile(A)-0.1% formic acid aqueous solution(B) as mobile phase for gradient elution, the flow rate was 0.3 mL·min–1 and the column temperature was 30 ℃. Mass spectrometry was performed using an electrospray ionization and data was collected in negative ion modes, and the detection range was m/z 80−1 200. The chemical constituents in Thamnolia subuliformis (Ehrh.) W.Culb. were identified rapidly and comprehensively based on the accurate relative molecular and combined with literature data and reference substances.
RESULTS
A total of 39 chemical constituents were speculatively identified, including 9 mono-substituted phenyl rings, 11 depsides, 5 depsidones, 2 dibenzofuran, 10 lipids, and 2 others.
CONCLUSION
The chemical constituents in the Thamnolia subuliformis (Ehrh.) W.Culb. can be identified accurately and rapidly by this method. Among them, 3 compounds(β-resorcylic acid, usnic acid, atranorin) are unambiguously identified by comparing with reference standards, 19 compounds are found from Thamnolia subuliformis (Ehrh.) W.Culb. for the first time. This paper can provide the important basis for study on pharmacodynamic material and substitute development of Thamnolia subuliformis (Ehrh.) W.Culb..
8.Guillain-Barre syndrome after allogeneic hematopoietic stem cell transplantation: a case report and literature review
Yajun SHI ; Ying HAN ; Ying WANG ; Rui ZHOU ; Rui SONG ; Dongfeng MAO ; Rui XI ; Hai BAI ; Tao WU
Chinese Journal of Hematology 2024;45(5):509-511
Guillain-Barre syndrome rarely develops after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and only a few reports exist in China. Guillain-Barre syndrome is an acute and life-threatening condition that requires early diagnosis and treatment. A patient with acute myeloid leukemia underwent allogeneic HSCT for >5 months and gradually developed limb muscle weakness and limited eye movement after coexisting with delayed acute intestinal graft-versus-host disease. After the examination of cerebrospinal fluid and electromyography, the diagnosis of Guillain–Barre syndrome was confirmed. After a high-dose intravenous immunoglobulin (IVIg) treatment, muscle strength gradually recovered, and the prognosis was good.
9.Integration of Intellectual Technology and Public Health:Creating Smart Healthy Cities
Xi WANG ; Danlei WANG ; Chongyi WANG ; Ayan MAO ; Xiaoling YAN ; Minjiang GUO ; Xiaohu MENG ; Wei WANG ; Wuqi QIU
Journal of Medical Informatics 2024;45(7):1-6
Purpose/Significance Based on the concepts of healthy cities and smart cities,the paper introduces a new concept-smart healthy cities.It explores the definition,scope,function,challenges,and strategic responses associated with the concept.Meth-od/Process Through literature review and case study analysis,the theoretical foundations,characteristics,objectives,and implementa-tion strategies of healthy cities and smart cities are compared,revealing differences and points of convergence,proposing the origins,def-initions,and delineations of smart healthy cities,and exploring the relationships among healthy cities,smart cities,and smart healthy cit-ies.Result/Conclusion Smart healthy cities enhance urban health governance and the well-being of residents through technological in-novation.Effective integration of advanced technologies with urban governance policies is essential,alongside the implementation of di-verse strategies to drive progress.Future urban development should focus more on the theoretical and practical collaborative development within the smart healthy cities framework.
10.The Technical Framework and Applications of Smart and Healthy City
Xiaohu MENG ; Wuqi QIU ; Tao YUN ; Haitian YU ; Xi WANG ; Xiaoling YAN ; Ayan MAO
Journal of Medical Informatics 2024;45(7):14-19
Purpose/Significance Based on the digital health community reference architecture,the technical framework for smart and healthy city is constructed to support the research and development of smart and healthy city.Method/Processs According to the ar-chitecture,combined with the needs and practices of the digitalization of the health industry,the"1+1+3+N"technical framework re-presenting the digital infrastructure and smart hub of the smart and healthy city is derived,namely,the one network,unified digital health foundation,three service platforms and N intelligent applications,application analysis is conducted.Result/Conclusion The framework can be used to crack the information interoperability problem,significantly release the value of medical and health data,and support in-dustry users and industry partners to hammer out scenario-based solutions for different business areas,and provide references for the top-level planning,construction and development of smart and healthy cities around the country.


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