1.Discovery and identification of EIF2AK2 as a direct key target of berberine for anti-inflammatory effects.
Wei WEI ; Qingxuan ZENG ; Yan WANG ; Xixi GUO ; Tianyun FAN ; Yinghong LI ; Hongbin DENG ; Liping ZHAO ; Xintong ZHANG ; Yonghua LIU ; Yulong SHI ; Jingyang ZHU ; Xican MA ; Yanxiang WANG ; Jiandong JIANG ; Danqing SONG
Acta Pharmaceutica Sinica B 2023;13(5):2138-2151
Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.
2.Evolution and development of potent monobactam sulfonate candidate IMBZ18g as a dual inhibitor against MDR Gram-negative bacteria producing ESBLs.
Zhiwen LI ; Zhihao GUO ; Xi LU ; Xican MA ; Xiukun WANG ; Rui ZHANG ; Xinxin HU ; Yanxiang WANG ; Jing PANG ; Tianyun FAN ; Yonghua LIU ; Sheng TANG ; Haigen FU ; Jingpu ZHANG ; Yinghong LI ; Xuefu YOU ; Danqing SONG
Acta Pharmaceutica Sinica B 2023;13(7):3067-3079
A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound 33a (IMBZ18G) is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant (MDR) Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with β-lactamase inhibitor avibactam, and the MIC values against MDR enterobacteria were reduced up to 4-512 folds. X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and C β-lactamases. Accordingly, preclinical studies of 33a alone and 33a‒avibactam combination as potential innovative candidates are actively going on, in the treatment of β-lactamase-producing MDR Gram-negative bacterial infections.
3.Association between age at menarche and prehypertension in female college students
WANG Yinghui, MA Yinghong, YAN Chi
Chinese Journal of School Health 2022;43(1):117-119
Objective:
To explore the correlation of age at menarche and prehypertension in female college students.
Methods:
Age at menarche of 558 female college students was collected, while blood pressure, height and weight were measured, and body mass index(BMI) was calculated.
Results:
Average age at menarche was (12.48±0.95) years, prevalence of prehypertension was 17.56% (98/558). The age of menarche was 8-11, 12, 13, 14, 15-19, and the prevalence of hypertension was 30.95%, 10.00% , 17.31%, 10.81%, 31.58% respectively, U shape association was observed in the association between prehypertension with age at menarche, lowest when age at menarche was <12 years. There was no significant difference in prehypertension between age at menarche was 13, 14 years old with 12-year-old group, those age at menarche 8-11 or 15-19 had a significantly higher risk of developing prehypertension than those 12-year-old( OR =4.03, 4.15, P <0.05).
Conclusion
Early or late menarche is associated with high blood pressure, appropriate intervention for girls with early menarche and obesity may be beneficial in reducing their future hypertension.
4.Gadoxetate-Enhanced MRI as a Diagnostic Tool in the Management of Hepatocellular Carcinoma:Report from a 2020 Asia-Pacific Multidisciplinary Expert Meeting
Cher Heng TAN ; Shu-cheng CHOU ; Nakarin INMUTTO ; Ke MA ; RuoFan SHENG ; YingHong SHI ; Zhongguo ZHOU ; Akira YAMADA ; Ryosuke TATEISHI
Korean Journal of Radiology 2022;23(7):697-719
Gadoxetate magnetic resonance imaging (MRI) is widely used in clinical practice for liver imaging. For optimal use, we must understand both its advantages and limitations. This article is the outcome of an online advisory board meeting and subsequent discussions by a multidisciplinary group of experts on liver diseases across the Asia-Pacific region, first held on September 28, 2020. Here, we review the technical considerations for the use of gadoxetate, its current role in the management of patients with hepatocellular carcinoma (HCC), and its relevance in consensus guidelines for HCC imaging diagnosis. In the latter part of this review, we examine recent evidence evaluating the impact of gadoxetate on clinical outcomes on a continuum from diagnosis to treatment decision-making and follow-up. In conclusion, we outline the potential future roles of gadoxetate MRI based on an evolving understanding of the clinical utility of this contrast agent in the management of patients at risk of, or with, HCC.
5.Finite element modeling of tibial fracture and its biomechanical analysis
Yinghong ZHAO ; Jie PING ; Renyuan WU ; Leyan MA ; Xianchao YU ; Cunjie SUN ; Hang XU
Military Medical Sciences 2016;40(12):988-993
Objective To establish CT image-based, three-dimensional finite element models of healthy tibiae and plateau-fracture tibiae, and to calculate the displacement and stress distribution of the tibial models .Methods Continuous-time tomographic images of knee joints of a healthy adult and a patient with tibial plateau fractures were obtained using multi-slice spiral CT scan , and inputed to Mimics to establish three-dimensional surface mesh models of tibiae .The models underwent global meshing procedures and material properties assignment to construct finite element models of normal and plateau-fracture tibiae in ANSYS , and the newly established models were analyzed and calculated .Results In case of applied load on the tibial plateau , the peak strains of the load-contact sites in the healthy subject and the patient presented divergent directions , with peak strains on the medial tibia in the healthy subject and lateral tibia in the patient , respectively . Equivalent stress decreased gradually down the tibiae and concentrated in the one -third of the upper and middle regions in both types of tibiae .Moreover, concentration of stress was also present in the locus of the fractured tibia .The deformation displacement gradients were more evident in the healthy tibia than in the fractured tibiae .There was significant difference in overall stress distribution between the two types of tibiae .Conclusion Three-dimensional finite element models of tibiae have been established that can demonstrate the differences in biomechanical properties between healthy and plateau -fracture tibiae, which might provide reference and guidance for orthopedic regimens .
6.Development of healthcare-associated infection management organizations in China in the past 30 years
Sidi LIU ; Chunhui LI ; Liuyi LI ; Tieying HOU ; Lili DING ; Weiping LIU ; Xiaoli LUO ; Hongqiu MA ; Jianguo WEN ; Yinghong WU ; Yawei XING ; Weiguang LI ; Huai YANG ; Yun YANG ; Weihong ZHANG ; Jian LIU ; Jianzhong XIE ; Anhua WU
Chinese Journal of Infection Control 2016;15(9):648-653
Objective To understand the development of healthcare-associated infection(HAI)management organ-izations in China in the past 30 years.Methods Development of HAI management organizations in 12 provinces (municipalities,autonomous regions)in China was surveyed.Results A total of 166 hospitals were surveyed,96 (57.83%)were tertiary hospitals.Among 164 hospitals which had a history of development of HAI management department,46(28.05%)before 1995,63(38.14%)in 1995-2005,and 55(33.54%)in 2005-2015 set up HAI management departments.HAI management professionals per 1 000 beds in 165 hospitals decreased from 4.80 in 1995 to 4.09 in 2015,occupational categories in HAI management departments in 1995 -2015 were significantly different (χ2 =26.22,P <0.01).The constituent ratios of education background and profession of HAI manage-ment professionals in each province in 1995-2015 were significantly different(χ2 =242.91,47.10,respectively,all P <0.01).In 1995 and 2005,70.81%,53.30% of professionals were with college degree or below;in 2015,the percentage of professionals with bachelor’s degree,doctoral degree,and master’s degree were 53.79%,2.45%, and 22.86% respectively.Most professionals were nursing staff,but the percentage decreased from 58.38% in 1995 to 45.96% in 2015.Conclusion Although HAI management organizations have developed for 30 years and made some achievements,there still remain some problems,the proportion of professionals needs to be enhanced,and personnel structure should be optimized.
7.Economic loss due to healthcare-associated infection in 68 general hospitals in China
Huixue JIA ; Tieying HOU ; Weiguang LI ; Hongqiu MA ; Weiping LIU ; Yun YANG ; Anhua WU ; Yinghong WU ; Huai YANG ; Lili DING ; Yunxi LIU ; Xiaoli LUO ; Jianguo WEN ; Yawei XING ; Weihong ZHANG ; Ling LIN ; Ying LI ; Meilian CHEN ; Liuyi LI
Chinese Journal of Infection Control 2016;15(9):637-641
Objective To explore the direct economic loss caused by healthcare-associated infection(HAI)in general hospitals in China.Methods 68 hospitals were selected,a retrospective 1:1 matched survey was conducted to compare the direct medical cost in patients with and without HAI between January 1,2015 and December 31,2015. Results A total of 2 123 pairs of patients with and without HAI were included in the survey.The average cost of hospitalization in HAI and non-HAI groups were ¥25 845.30 and ¥12 006.14 respectively,¥13 839.16 on average was increased due to HAI.The average economic loss in provincial and ministerial levels of hospitals were¥21 409.83.The average economic loss in different regional hospitals were ¥9 725.42-¥18 909.59,and north China ranked the first.Economic loss caused by bloodstream infection and lower respiratory tract infection were more than other sites,which were ¥23 190.09 and ¥18 194.50 respectively.Conclusion HAI resulted in considerable direct economic loss.Prevention and control of HAI,especially bloodstream infection and lower respiratory tract infection should be paid more attention.
8.Occupational exposure and protection among health care workers in China
Jian SUN ; Hua XU ; Anman GU ; Weiguang LI ; Anhua WU ; Yunxi LIU ; Huai YANG ; Lili DING ; Hongqiu MA ; Yun YANG ; Yawei XING ; Ling LIN ; Weiping LIU ; Xiaoli LUO ; Jianguo WEN ; Weihong ZHANG ; Tieying HOU ; Yinghong WU
Chinese Journal of Infection Control 2016;15(9):681-685
Objective To understand the current situation of occupational exposure and protection among health care workers (HCWs ), and provide evidence for formulating preventive measures of occupational exposure. Methods From April 6,2016 to May 6,2016,questionnaire surveys were conducted in 158 different levels of hos-pitals in 13 provinces in China,occupational exposure,protection management,and monitoring of occupational expo-sure in the first year,2010,and 2015 was surveyed by cluster random sampling method.Results Occupational ex-posure in 81.65% (129/158)of hospitals was responsible by healthcare-associated infection management depart-ments;98.73%(156/158)of hospitals set up the relevant rules and regulations;77.22%(122/158)of hospitals had missing report of occupational exposure.A total of 11 116 times of occupational exposure occurred (1 542 cases in the first year,2 474 in 2010,and 7 100 in 2015).Of various types of occupational exposure,sharp injury accounted for 96.76%;among HCWs sustained occupational exposure,nursing staff accounted for 53.90%;the major de-partment that HCWs who sustained occupational exposure were general wards,operating rooms,and intensive care units;the main medical appliances related to occupational exposure were syringes,scalp needles,and surgical suture needles;high-risk behavior causing occupational exposure were intravenous injection,putting needles into the sharp con-tainers,and surgical suturing;among occupational exposure sources,HBV accounted for 58.69%.Conclusion HCWs in China face a high risk of occupational exposure,occurrence of occupational exposure should be reduced through gov-ernment legislation,application of safety appliances,standardizing behavior of HCWs,proper using of personal pro-tective equipment,strengthening education and training of HCWs,and establishing a sound occupational exposure report,evaluation and follow-up system.
9.Development situation of healthcare-associated infection management de-partments in the rational antimicrobial application and management in China
Chunhui LI ; Sidi LIU ; Liuyi LI ; Tieying HOU ; Lili DING ; Weiping LIU ; Xiaoli LUO ; Hongqiu MA ; Jianguo WEN ; Yinghong WU ; Yawei XING ; Weiguang LI ; Huai YANG ; Yun YANG ; Weihong ZHANG ; Jian LIU ; Jianzhong XIE ; Anhua WU
Chinese Journal of Infection Control 2016;15(9):665-670
Objective To understand the development situation of healthcare-associated infection (HAI)manage-ment departments in the rational antimicrobial application and management in hospitals in China.Methods A total of 166 hospitals from 12 provinces,municipalities,autonomous regions,and military hospitals were selected for survey,the participation of HAI management departments in the rational clinical antimicrobial application and man-agement in different years was compared.Results Of 166 hospitals,68(40.96%)in 2005,119(71.69%)in 2010, and 160(96.39%)in 2015 participated in the establishment of management organizations for rational antimicrobial application (χ2 =121.143,P <0.001).The percentage of HAI management departments participating in antimicro-bial management increased from 10.24%(n=17)in 2005 to 22.29%(n=37)in 2010,and 31.33%(n=52)in 2015 (χ2 =22.172,P < 0.001 ).The percentages of HAI management departments participating in formulating cata-logues for antimicrobial varieties and classification,stipulating permission for antimicrobial use,joining antimicrobi-al management teams,monitoring bacterial resistance,managing antimicrobial prophylaxis in clean incision,super-vising clinical antimicrobial use,conducting clinical consultation,and evaluating prescription were 10.87% -30.72% in 2005,25.90%-65.06% in 2010,and 36.14%-95.18% in 2015 (all P <0.01).Intensity of antimicro-bial use (defined daily dose/100 bed-days,DDD/ 100 bed-days)decreased from 69.16 in 2005 to 41.40 in 2015, antimicrobial usage rate decreased from 46.98% in 2005 to 36.90% in 2015,among patients receiving therapeutic antimicrobial use,specimens sending for pathogenic detection increased from 20.58% in 2005 to 49.39% in 2015. Conclusion Departments of HAI management in China play important role in management of rational antimicrobial application.
10.Development and changing trend in monitoring of healthcare-associated in-fection in China
Nan REN ; Ximao WEN ; Chenchao FU ; Liuyi LI ; Tieying HOU ; Lili DING ; Weiping LIU ; Xiaoli LUO ; Hongqiu MA ; Jianguo WEN ; Yinghong WU ; Yawei XING ; Weiguang LI ; Huai YANG ; Yun YANG ; Weihong ZHANG ; Yunxi LIU ; Ling LIN ; Anhua WU
Chinese Journal of Infection Control 2016;15(9):642-647
Objective To summarize the effectiveness in monitoring activities for healthcare-associated infection (HAI)in China in the past 30 years,explore the changing trend in HAI monitoring,find a new model for the moni-toring of HAI in China.Methods A total of 194 comprehensive hospitals and military hospitals in 13 provinces (au-tonomous regions,municipalities)were selected,questionnaire survey was adopted to investigate the situation of HAI monitoring.Results Of 194 hospitals,184 (94.85%)had available data after being checked,incidence of HAI in secondary and tertiary hospitals were 0.78% and 1.58% respectively,difference was significant (P <0.01).Monitoring was divided into two stages,cumulative percentage of each monitoring activity before 2006 and during 2006-2016 were respectively as follows:environmental hygiene were 73.91% and 100.00%,disinfection ef-ficacy 69.57% and 97.28%,overall comprehensive monitoring 64.67% and 98.91%,surgical site infection(SSI) 13.04% and 94.57%,ICU HAI 4.89% and 87.50%,neonatal HAI 1.75% and 60.82%,multidrug-resistant or-ganisms(MDROs)5.43% and 95.65%,hand hygiene compliance 2.17% and 93.48%,antimicrobial agents 15.22% and 87.50%.The reporting rate of HAI outbreak in tertiary hospitals was higher than secondary hospitals (33.33% [n=37]vs 16.44%[n=12],P =0.01).Conclusion The monitoring of HAI in China starts late,but develops rapidly,defects still exist in HAI monitoring system,reporting rate of HAI cases is still high,reporting rate of HAI outbreak is low.


Result Analysis
Print
Save
E-mail