1.Recent advances in small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase
Hui-nan JIA ; Rui-fang JIA ; Ji-wei ZHANG ; Yuan-min JIANG ; Chuan-feng LIU ; Ying ZHANG ; Xin-yong LIU ; Peng ZHAN
Acta Pharmaceutica Sinica 2024;59(1):43-60
Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.
2.Design of intelligent positioning system for mobile medical equipment in operating room based on Bluetooth technology
Zhi-Meng LIU ; Ya-Dong LYU ; Long-Xue QIAO ; Lin-Huai TIAN ; Kun YANG ; Kai-Yuan LI ; Ning-Bo ZHAN ; Ying-Kang WEI ; Yong CHAO
Chinese Medical Equipment Journal 2023;44(9):29-32
Objective To develop an intelligent positioning system for mobile medical equipment in the operating room based on Bluetooth technology to enhance medical equipment management efficiency.Methods The intelligent positioning system for mobile medical equipment used received signal strength indication(RSSI)algorithm and multi-gateway trajectory filtering algorithm to realize Bluetooth positioning,which was composed of Bluetooth gateways,Bluetooth beacons,Bluetooth labels and a background data processing platform.The Bluetooth gateway consisted of an active power over ethernet(POE)module,a DC power module,a CPU,a Wi-Fi module and a Bluetooth module;the Bluetooth beacon included a beacon control unit,a Bluetooth transmitter module and a Bluetooth receiver module;the Bluetooth label was made up of a microcontroller unit(MCU),a Bluetooth module,an anti-temper switch and a accelerometer;the data processing platform had the front end developed with Vue architecture and the back end with Java language.Results The system developed could accurately locate the medical equipment in the operating room without electromagnetic interference to other medical devices.Conclusion The system developed gains advantages in high positioning accuracy,low electromagnetic interference,high stability and reliability and low cost,which improves the positioning and management efficiency of medical equipment under the premise of ensuring safety.[Chinese Medical Equipment Journal,2023,44(9):29-32]
3.Construction and validation of a Nomogram model of intracranial infection after neurosurgery
Xiao-Ju MA ; Ying YU ; Yan LU ; Song-Qin LI ; Juan LIU ; Zheng WANG ; Feng ZANG ; Hui-Ping HUANG ; You-Peng CHEN ; Yong-Xiang ZHANG ; Wei-Hong ZHANG ; Zhan-Jie LI
Chinese Journal of Infection Control 2023;22(12):1483-1492
Objective To explore the risk factors for intracranial infection in patients after neurosurgery,con-struct and validate a Nomogram prediction model.Methods Data of 978 patients who underwent neurosurgery in a hospital in Nanjing from January 1,2019 to December 31,2022 were retrospectively analyzed.Independent risk fac-tors were screened through logistic univariate and multivariate analyses.Modeling variables were screened through Lasso regression.A Nomogram model was constructed and internally validated by logistic regression.Effectiveness of the model was evaluated with receiver operating characteristic(ROC)curve,calibration curve and decision curve.Results Among 978 patients underwent neurosurgery,293 had postoperative intracranial infection,with an inci-dence of healthcare-associated infection of 29.96%.There was no significant difference in age,gender,proportion of coronary heart disease,cerebral infarction,diabetes and hypertension between the infected group and the non-in-fected group(all P>0.05).Multivariate logistic analysis showed that postoperative intracranial hypertension,fe-ver,increased neutrophil percentage in blood routine examination,turbid cerebrospinal fluid,positive Pan's test,decreased glucose concentration,abnormal ratio of cerebrospinal fluid/serum glucose,positive microbial culture,absence of indwelling external ventricular drainage tubes,presence of indwelling lumbar cistern drainage tubes,use of immunosuppressive agents,and long duration of surgery were independent risk factors for postoperative intracra-nial infection in patients who underwent neurosurgery(all P<0.05).Fifteen variables were screened out through Lasso regression.Fourteen variables were finally included for modeling after collinear screening,missing data impu-tation(random forest method)and checking pairwise interaction items.A Nomogram prediction model was con-structed,with the area under ROC curve,sensitivity,specificity,and accuracy of 0.885,0.578,0.896,and 0.704,respectively.Internal validation of the model was conducted.The modeling and validation groups presented similar effects.The calibration curve and decision curve also indicated that the model had good predictive efficacy.Conclusion The constructed Nomogram prediction model for postoperative intracranial infection after neurosurgery is scientific,and the prediction indicators are easy to obtain.The model presents with high stability,reliability,and application value,thus can provide reference for the assessment of postoperative intracranial infection after neuro-surgery.
4.Recent advances in small-molecule inhibitors targeting influenza virus glycoproteins
Yuan-min JIANG ; Ji-wei ZHANG ; Rui-fang JIA ; Hui-nan JIA ; Ying ZHANG ; Xin-yong LIU ; Peng ZHAN
Acta Pharmaceutica Sinica 2023;58(11):3254-3269
Hemagglutinin and neuraminidase, two important glycoproteins on the surface of influenza virus, play a considerable role in the entry and release stage of the viral life cycle, respectively. With in-depth investigation of influenza virus glycoproteins and the continuous innovation of drug discovery strategies, a new generation of glycoproteins inhibitors have been continuously discovered. From the point of view of medicinal chemistry, this review summarizes the current advances in seeking small-molecule inhibitors targeting influenza virus glycoproteins, hoping to provide valuable guidance for future development of novel antiviral drugs.
5.Advances in the research of HIV-1 envelope glycoprotein gp120 inhibitors
Ming-hui XIE ; Zhao WANG ; Yan-ying SUN ; Xiang-yi JIANG ; Peng ZHAN ; Xin-yong LIU ; Dong-wei KANG
Acta Pharmaceutica Sinica 2023;58(3):616-628
From the process of human immunodeficiency virus-1 (HIV-1) invading cells, the combination of gp120 and CD4 is the first step for HIV-1 to invade cells. Interfering with this process can prevent HIV from recognizing target cells and inhibit virus replication. Therefore, HIV-1 gp120 is an important part of the HIV-1 life cycle. Fostesavir, a phosphatate prodrug derived from the gp120 inhibitor BMS-626529 modified by the prodrug strategy, was approved for the treatment of adult patients with multidrug resistant HIV-1 infection by the US FDA and the European Medicines Agency in 2020 and 2021, respectively. In this review, we focus on the research progress of small molecule inhibitors targeting the interaction of gp120-CD4 from the perspective of medicinal chemistry, in order to provide reference for the subsequent research of gp120 inhibitors.
6.Efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma.
Zhao Gan REN ; Yu XU ; Zhan qiang HUA ; Zong Yi MO ; Luo Wen WANG ; Gen Bing SHI ; Wan Lin LIU ; Wei SUN ; Bi Qiang ZHENG ; Chun Meng WANG ; Yong Jia JIN ; Yong CHEN
Chinese Journal of Oncology 2023;45(11):973-980
Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.
Humans
;
Antibodies, Monoclonal/therapeutic use*
;
Apoptosis
;
China
;
Disease-Free Survival
;
East Asian People
;
Immunotherapy
;
Interferon-alpha/therapeutic use*
;
Lymphatic Metastasis
;
Melanoma/pathology*
;
Programmed Cell Death 1 Receptor/therapeutic use*
;
Skin Neoplasms/pathology*
;
Melanoma, Cutaneous Malignant
7.Efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma.
Zhao Gan REN ; Yu XU ; Zhan qiang HUA ; Zong Yi MO ; Luo Wen WANG ; Gen Bing SHI ; Wan Lin LIU ; Wei SUN ; Bi Qiang ZHENG ; Chun Meng WANG ; Yong Jia JIN ; Yong CHEN
Chinese Journal of Oncology 2023;45(11):973-980
Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.
Humans
;
Antibodies, Monoclonal/therapeutic use*
;
Apoptosis
;
China
;
Disease-Free Survival
;
East Asian People
;
Immunotherapy
;
Interferon-alpha/therapeutic use*
;
Lymphatic Metastasis
;
Melanoma/pathology*
;
Programmed Cell Death 1 Receptor/therapeutic use*
;
Skin Neoplasms/pathology*
;
Melanoma, Cutaneous Malignant
8.Molluscicidal effect of immersion with 50% wettable powder of niclosamide ethanolamine salt against Oncomelania hupensis on the soil surface and inside the soil layer in winter
Wei-chun WANG ; Ti ZHAN ; Ze-han FAN ; Ke-xia XIANG ; Ying-fu ZHU ; Yong-mei DUAN ; Zhi-guo CAO
Chinese Journal of Schistosomiasis Control 2022;34(4):396-399
Objective To evaluate the molluscicidal effect of 50% wettable powder of niclosamide ethanolamine salt (WPNES) against Oncomelania hupensis on the soil surface and inside the soil layer by immersion method in winter. Methods O. hupensis snails were placed on the soil surface and 2, 5 cm and 10 cm under the soil layer outdoors in winter, and then immersed in 50% WPNES at concentrations of 1 mg/L and 2 mg/L for 1, 3 d and 7 d, while dechlorinated water served as controls. Snail mortality was observed following immersion with 50% WPNES on the soil surface and inside the soil layer. Results Following immersion with 50% WPNES at concentrations of 2 mg/L and 1 mg/L outdoors in winter, the 3-day corrected snail mortality rates were 98.0% and 76.0% on the soil surface, and the 7-day corrected snail mortality rate was both 100.0%. Following immersion with 50% WPNES at concentrations of 2 mg/L and 1 mg/L outdoors in winter, the 7-day corrected snail mortality rates were 95.5% and 85.6% 2 cm below the soil layer, 66.0% and 6.4% 5 cm below the soil layer. However, the 7-day snail mortality rate swere comparable between the 50% WPNES treatment group (at 2 mg/L and 1 mg/L) and controls 10 cm below the soil layer (both P > 0.05). Conclusion Immersion of 50% WPNES at a concentration of 2 mg/L for 7 days presents a high molluscicidal efficacy against O. hupensis on the soil surface and 5 cm within the soil layers in winter.
9.Clinical significance of bispectral index monitoring in patients with acute severe carbon monoxide poisoning.
Jia LI ; Long LI ; Yong Jian LIU ; Wei Zhan WANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2022;40(5):337-340
Objective: To analyze the correlation of bispectral index (BIS) with the prognosis of patients with acute severe carbon monoxide poisoning (ASCMP) and its predictive value of adverse outcomes. Methods: In March 2021, 106 ASCMP patients who were treated in Harrison International Peace Hospital Affiliated to Hebei Medical University from January 2019 to December 2020 were taken as research objects. All patients underwent 24-hour BIS monitoring after admission, and were divided into good prognosis group (n=75) and poor prognosis group (n=31) according to the prognosis of the patients' cranial nerve function after 60 d. The general conditions, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHEⅡ) score, Glasgow Coma Scale (GCS) score at admission and 24-hour BIS mean were compared between the two groups. Pearson correlation analysis was used to analyze the correlations between the 24-hour BIS mean and GCS score at admission, APACHEⅡ score and coma time. The receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of 24-hour BIS mean, GCS score at admission, APACHEⅡ score and coma time on adverse outcome of ASCMP patients. Results: The coma time and APACHEⅡ score of the patients in the poor prognosis group were significantly higher than those in the good prognosis group, the GCS score at admission and 24-hour BIS mean were significantly lower than those in the good prognosis group (P<0.05) . Pearson correlation analysis showed that the 24-hour BIS mean was positively correlated with the GCS score at admission, and negatively correlated with the APACHEⅡ score, coma time (r=0.675, -0.700, -0.565, P<0.001) . The 24-hour BIS mean had the highest predictive value for adverse outcome of ASCMP patients, with a cut-off value of 74, the area under the curve was 0.883 (95%CI: 0.814-0.951, P<0.001) , and the sensitivity and specificity were 73.3% and 87.1%, respectively. Conclusion: The 24-hour BIS mean has a good correlation with the acute brain nerve injury, the severity of the disease and coma time of patients with ASCMP. And it has a high predictive value for the adverse outcome in patients with ASCMP.
APACHE
;
Brain Injuries
;
Carbon Monoxide Poisoning/diagnosis*
;
Coma
;
Humans
;
Prognosis
;
ROC Curve
;
Retrospective Studies
;
Sensitivity and Specificity
10.Relevant thoughts on development of traditional Chinese medicine industry in new era.
Ju HUANG ; Geng LI ; Xiao-Xiao ZHANG ; Yong MA ; Zhi-Lai ZHAN ; Wei-An YUAN ; Li-Ping QU ; Shi-Yao HUANG ; Bo LI ; Bo-Hua YAN ; Wen-Yuan LI ; Li LIU ; Zhi-Lei WANG ; Yi FENG ; Lei ZHANG ; Jian-Yuan TANG
China Journal of Chinese Materia Medica 2022;47(17):4799-4813
Since the 18th National Congress of the Communist Party of China(CPC), the CPC and the government have highligh-ted the development of traditional Chinese Medicine(TCM) and issued a series of policies, such as the Plan for Protection and Deve-lopment of Chinese Medicinal Materials(2015-2020) forwarded by the General Office of the State Council in 2015, the Plan for Healthy Development of Traditional Chinese Medicine(2015-2020) released by the General Office of the State Council in the same year, the Healthy China 2030 Plan published by the CPC Central Committee and the State Council in 2016, the Law of the People's Republic of China on Traditional Chinese Medicine which took effect on July 2017, On the Preservation and Innovative Development of Traditional Chinese Medicine promulgated by CPC Central Committee and the State Council in 2019, and Plan for the Development of Traditional Chinese Medicine during the 14th Five-Year Plan Period of China released by the General Office of the State Council in March 2022, to promote the development of the TCM industry, which have brought historical opportunities to the TCM industry. However, TCM industry faces various challenges in the development. In terms of drug development in TCM, the current studies mainly focused on the chemical research and technical requests, which neglected TCM characteristics and cased in conformity between new drug transformation of TCM and clinical practice. Therefore, a more considerable and profound authoritative guideline is needed, and innovative thought and research are necessary for academics and the industry. Through the investigation of the development TCM industry in recent years, this study summarized the policies on and trends of Chinese medicinal materials, new drug development in TCM, catalogue of national basic drugs, and national basic health insurance, and proposed suggestions for further development of TCM industry.
China
;
Drugs, Chinese Herbal
;
Humans
;
Industry
;
Medicine, Chinese Traditional
;
Policy

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