1."Weibing" in traditional Chinese medicine-biological basis and mathematical representation of disease-susceptible state.
Wanyang SUN ; Rong WANG ; Shuhua OUYANG ; Wanli LIANG ; Junwei DUAN ; Wenyong GONG ; Lianting HU ; Xiujuan CHEN ; Yifang LI ; Hiroshi KURIHARA ; Xinsheng YAO ; Hao GAO ; Rongrong HE
Acta Pharmaceutica Sinica B 2025;15(5):2363-2371
"Weibing" is a fundamental concept in traditional Chinese medicine (TCM), representing a transitional state characterized by diminished self-regulatory abilities without overt physiological or social dysfunction. This perspective delves into the biological foundations and quantifiable markers of Weibing, aiming to establish a research framework for early disease intervention. Here, we propose the "Health Quadrant Classification" system, which divides the state of human body into health, sub-health, disease-susceptible state, and disease. We suggest the disease-susceptible stage emerges as a pivotal point for TCM interventions. To understand the intrinsic dynamics of this state, we propose laboratory and clinical studies utilizing time-series experiments and stress-induced disease susceptibility models. At the molecular level, bio-omics technologies and bioinformatics approaches are highlighted for uncovering intricate changes during disease progression. Furthermore, we discuss the application of mathematical models and artificial intelligence in developing early warning systems to anticipate and avert the transition from health to disease. This approach resonates with TCM's preventive philosophy, emphasizing proactive health maintenance and disease prevention. Ultimately, our perspective underscores the significance of integrating modern scientific methodologies with TCM principles to propel Weibing research and early intervention strategies forward.
2.Artesunate inhibits proliferation and promotes apoptosis and autophagy of nephroblastoma cell line SK-NEP-1
Jianxin WEI ; Yanle FANG ; Yubo LU ; Yuguang GAO ; Xing LANG ; Jingtao LI ; Xinsheng MA
Basic & Clinical Medicine 2025;45(4):493-498
Objective To investigate the effects of artesunate(Art)on the proliferation,apoptosis,and autophagy of nephroblastoma cell line(SK-NEP-1).Methods SK-NEP-1 cells were intervened with different concentrations of Art(0,10,20,40 and 80 μmol/L),and MTT method was applied to calculate the cell proliferation inhibition rate to screen the optimal intervention concentration;SK-NEP-1 cells were separated into control group,Art group,3-MA group(Art+autophagy inhibitor,3-methyladenine),and Rapa group(Art+autophagy activator rapamycin).EdU and flow cytometry were applied to detect cell proliferation and apoptosis,respectively;MDC staining was applied to detect autophagy in cells;the level of reactive oxygen species(ROS)in cells was detected by DCFH-DA fluorescent probe;the expression of proliferating cell nuclear antigen(PCNA),anti apoptotic factor B cell lym-phomatoma-2(Bcl-2),Bcl-2 associated X protein(Bax),microtubule junction protein 1 light chain 3 Ⅱ/3 Ⅰ(LC3 Ⅱ/LC3 Ⅰ),selective autophagy junction protein 1(p62),and benzyl chloride 1(Beclin-1)proteins in cells were detected by Western blot.Results Compared with 0 μmol/L Art,the proliferation inhibition rate of SK-NEP-1 cells was gradually increased after 10,20,40 and 80 μmol/L Art treatment(P<0.05),and the IC50 value was 46.881 μmol/L,so 40 μmol/L Art was selected for follow-up experiments.Compared with the control group,the apoptosis rate,relative autophagy fluorescence intensity,ROS level,Bax,LC3 Ⅱ/LC3 Ⅰ,Beclin-1,PINK1,and Parkin protein expression levels of SK-NEP-1 cells in the Art group were obviously increased,the EdU positive cell rate,PCNA,Bcl-2,and P62 protein expression levels were obviously reduced(P<0.05);The auto-phagy inhibitor 3-MA inhibited the promoting effect of Art on apoptosis and autophagy of nephroblastoma cells and inhibit proliferation(P<0.05).Conclusions Art inhibits the proliferation of nephroblastoma cell line SK-NEP-1,and promotes autophagy and apoptosis.
3.Real-time evaluation of pulmonary ventilation of HP movements based on electrical impedance tomography:an observational study
Zhijun GAO ; Hang WANG ; Chunchen WANG ; Yilong QIN ; Xinsheng CAO ; Lin YANG
Journal of Army Medical University 2024;46(16):1882-1889,1896
Objective To explore the feasibility of electrical impedance tomography(EIT)for real-time and accurate monitoring of respiration during HP anti-G movements and the key parameters of pulmonary ventilation.Methods Twelve healthy male students in our university were enrolled in September 2023 and subjected in this study.HP anti-G movements were performed 3 times each for 30 s in the anti-G physiological training apparatus,during which EIT and ophthalmic horizontal arterial pressure were measured to analyze the relationship of the global and local parameters of pulmonary ventilation,including inspiratory volume(IV),expiratory uniform(EU),expiratory speed(ES),center of ventilation(COV)and right-to-left lung ventilation ratio(RtoL)with anti-G ability of anti-G straining maneuver(AGSM).Results The average eye horizontal systolic blood pressure(SBP)at the eye level was 148.82±22.75 mmHg during HP anti-G movements,which was significantly higher than that during quiet breathing(PJ)(95.17±8.51 mmHg,P<0.001).From the global pulmonary ventilation,the participants had significantly increased IV during HP anti-G movements(P<0.001).According the d value(mean increase of eye horizontal SBP=SBPHP-SBPPJ),the subjects were divided into 3 groups,with the d value of>60,30~60 and<30 mmHg,respectively.The inspiratory volume ratio(IVHP/IVPJ)was the highest in the>60 mmHg group and the smallest in the<30 mmHg group(P<0.01).The subjects had significantly decreased EU and more evenly expiration(P<0.05),but no change was seen in the expiratory uniformity ratio(EUHP/EUPJ)among the 3 groups.ES was obviously faster during HP anti-G movements(P<0.001),and the expiratory speed ratio(ESHP/ESPJ)had no significant difference among the 3 groups.The inspiratory time and expiratory time were 0.77±0.32 and 1.59±0.21 s,respectively,and both of them were notably shorter during HP anti-G movements(P<0.001,P<0.01).From the local pulmonary ventilation,COV during HP anti-G movements was significantly smaller than that during PJ(P<0.001),and the ventilation center deviated to the ventral side,and RtoL was decreased and the ventilation distribution deviated to the left lung(P<0.05).Conclusion EIT can perform real-time imaging of pulmonary global and local ventilation during HP anti-G movements,and it has a great application prospect in AGSM training and monitoring.
4.Anterior cervical release and posterior fixation for the treatment of irreducible atlantoaxial dislocation with retropharyngeal internal carotid artery
Kun GAO ; Zhenghong YU ; Jia SHAO ; Kezheng MAO ; Xinsheng ZHANG ; Yanzheng GAO
Chinese Journal of Orthopaedics 2023;43(7):430-437
Objective:To investigate the clinical effect of anterior cervical release and posterior fixation in the treatment of irreducible atlantoaxial dislocation with retropharyngeal internal carotid artery.Methods:Thirteen patients with irreducible atlantoaxial dislocation of retropharyngeal internal carotid artery from January 2015 to July 2019 were treated with anterior cervical release and posterior fixation. There were 8 males and 5 females, aged from 34 to 65 years with an average of 46.1±12.6 years. Positive, lateral and dynamic X-ray films, MR and CTA were performed before operation. There were 4 cases with bilateral retropharyngeal internal carotid artery and 9 cases with unilateral retropharyngeal internal pharyngeal artery. The time of operation, the amount of bleeding and intraoperative and postoperative complications were recorded. The main observations were Japanese Orthopaedic Association (JOA) score, atlantodental interval (ADI), Chamberlain line (CL), and changes in the morphology of the retropharyngeal internal carotid artery and implant fusion.Results:All the operations completed successfully. The operation time was 210-260 min, the average was 245±21 min; the blood loss was 350-600 ml, the average blood loss was 490±107 ml. There was no injury of internal carotid artery, vertebral artery, spinal cord or nerve root during the operation. All patients were followed up for 9 to 24 months, with an average of 15.1±6.2 months. Preoperative JOA score was 6.9±2.3 points, 1 month after operation was 13.5±2.5 points, and the last follow-up was 14.3±2.1 points. The difference was statistically significant ( F=30.91, P<0.001). The difference between 1 month after operation and before operation was statistically significant ( P<0.001), and the improvement rate of JOA score was 75.6%±15.2%. There was no significant difference between the last follow-up and 1 month after operation ( P>0.05). The preoperative ADI was 8.9±2.2 mm, 1 month after operation was 1.1±0.8 mm, and the last follow-up was 1.2±0.9 mm. The difference was statistically significant ( F=114.69, P<0.001). The difference between 1 month after operation and before operation was statistically significant ( P<0.001), and ADI had returned to normal level. There was no significant difference between the last follow-up and 1 month after operation ( P>0.05). The preoperative CL was 11.7±4.8 mm, 1 month after operation was 1.6±2.1 mm, and the last follow-up was 1.8±2.3 mm. The difference was statistically significant ( F=34.19, P<0.001). The difference between 1 month after operation and before operation was statistically significant ( P<0.001), and the position of odontoid process returned to normal level. There was no significant difference between the last follow-up and 1 month after operation ( P>0.05). Bone graft fusion was received at 6 to 12 months after operation, with an average of 10.2 months. Conclusion:CTA examination should be performed before anterior release of atlantoaxial dislocation to understand the position and shape of internal carotid artery. Anterior cervical release combined with posterior bone graft fusion is an effective method for the treatment of irreducible atlantoaxial dislocation with retropharyngeal internal carotid artery without increasing the risk of internal carotid artery injury.
5.Extensive expansion of the chemical diversity of fusidane-type antibiotics using a stochastic combinational strategy.
Xiaojun SONG ; Jianming LV ; Zhiqin CAO ; Huiyun HUANG ; Guodong CHEN ; Takayoshi AWAKAWA ; Dan HU ; Hao GAO ; Ikuro ABE ; Xinsheng YAO
Acta Pharmaceutica Sinica B 2021;11(6):1676-1685
Fusidane-type antibiotics, represented by helvolic acid, fusidic acid and cephalosporin P
6.Expression of CDC45 in hepatocellular carcinoma and its correlation with prognosis
Yuan GAO ; Xinsheng XU ; Hui ZHANG
International Journal of Biomedical Engineering 2021;44(5):352-356
Objective:To analyze the expression of cell differentiation cyclin 45 (CDC45) in hepatocellular carcinoma (HCC) tissues, to explore the relationship between CDC45 and the prognosis of HCC, and to explore the possibility of CDC45 as a potential biomarker and therapeutic target for HCC.Methods:Bioinformatics methods were used to analyze the mRNA levels of CDC45 in HCC tissues and normal tissues, and to analyze the relationship between its expression and the survival rate of HCC patients. The clinicopathological data of 90 patients with HCC undergoing surgical treatment were retrospectively analyzed. Immunohistochemical method was used to detect the expression level of CDC45 protein in HCC tissue and normal tissues, and to analyze its relationship with clinicopathological characteristics of patients with HCC.Results:CDC45 is highly expressed in colorectal cancer, breast cancer, prostate cancer, lung cancer, liver cancer, etc. The expression of CDC45 in HCC tissues was higher than that in normal tissues adjacent to cancer ( P<0.05). The expression of CDC45 is significantly related to the clinical prognosis of HCC patients ( P<0.001), and the higher the expression of CDC45, the lower the disease-free survival rate and overall survival rate of HCC patients. CDC45 level is significantly correlated with the number of tumor nodules ( P=0.003) and tumor size ( P=0.003) in HCC patients, but the correlation between CDC45 level and age, gender and alpha-fetoprotein (AFP) levels is not statistically significant (all P>0.05). Conclusions:CDC45 plays an important role in the progression of HCC and is expected to become a therapeutic target and potential biomarker for HCC.
7.Tripodalsporormielones A-C, unprecedented cage-like polyketides with complex polyvdent bridged and fused ring systems.
Guodong CHEN ; Bingxin ZHAO ; Meijuan HUANG ; Jia TANG ; Yanbing LI ; Liangdong GUO ; Rongrong HE ; Dan HU ; Xinsheng YAO ; Hao GAO
Acta Pharmaceutica Sinica B 2021;11(11):3648-3654
A chemical investigation on
8.A four-protein metabolon assembled by a small peptide protein creates the pentacyclic carbonate ring of aldgamycins.
Qiaozhen WANG ; Xiaolong TANG ; Ping DAI ; Chuanxi WANG ; Weiyang ZHANG ; Guodong CHEN ; Kui HONG ; Dan HU ; Hao GAO ; Xinsheng YAO
Acta Pharmaceutica Sinica B 2021;11(2):588-597
Organic carbonates (OCs) are a class of compounds featured by a carbonyl flanked by two alkoxy/aryloxy groups. They exist in either linear or cyclic forms, of which the majority encountered in nature adopt a pentacyclic structure. However, the enzymatic basis for pentacyclic carbonate ring formation remains elusive. Here, we reported that a four-protein metabolon (AlmUII-UV) assembled by a small peptide protein (AlmUV) appends a reactive
9. Early antiviral therapy of abidor combined with lopinavir/ritonavir and re-combinant interferonα-2b in patients with novel coronavirus pneumonia in Zhejiang: A multicenter and prospective study
Runan WEI ; Nanhong ZHENG ; Xiangao JIANG ; Chunlian MA ; Xiaowei XU ; Shourong LIU ; Yongping CHEN ; Kaijin XU ; Hainv GAO ; Jiansheng ZHU ; Qiang SHU ; Jifang SHENG ; Xiaoqiang ZHANG ; Minghui LI ; Yan ZHANG ; Mengjie MA ; Xuan ZHANG ; Shibo LI ; Qiujing WANG ; Lingjun YING ; Yongjun ZHANG ; Yunzhen SHI ; Lingyan FAN ; Wanjun YU ; Huaying WANG ; Dandan SUN ; Xiaodong WANG ; Jichan SHI ; Yinghu CHEN ; Xinsheng XIE ; Yunqing CHEN ; Weihong WANG ; Zhaowei TONG ; Lingling TANG ; Mengfei ZHU ; Lingjian ZHANG ; Lanjuan LI
Chinese Journal of Clinical Infectious Diseases 2020;13(0):E010-E010
Objective:
Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province.
Methods:
A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data.
Results:
The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (
10.Early antiviral therapy of abidol combined with lopinavir/ritonavir and recombinant interferon α-2b for patients with COVID-19 in Zhejiang: A multicenter prospective study
Runan WEI ; Nanhong ZHENG ; Xiangao JIANG ; Chunlian MA ; Xiaowei XU ; Shourong LIU ; Yongping CHEN ; Kaijin XU ; Hainv GAO ; Jiansheng ZHU ; Qiang SHU ; Jifang SHENG ; Xiaoqiang ZHANG ; Minghui LI ; Yan ZHANG ; Mengjie MA ; Xuan ZHANG ; Shibo LI ; Qiujing WANG ; Lingjun YING ; Yongjun ZHANG ; Yunzhen SHI ; Lingyan FAN ; Wanjun YU ; Huaying WANG ; Dandan SUN ; Xiaodong WANG ; Jichan SHI ; Yinghu CHEN ; Xinsheng XIE ; Yunqing CHEN ; Weihong WANG ; Zhaowei TONG ; Lingling TANG ; Mengfei ZHU ; Lingjian ZHANG ; Lanjuan LI
Chinese Journal of Clinical Infectious Diseases 2020;13(1):9-15
Objective:To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon α-2b (rIFNα-2b) and the combination of lopinavir/ritonavir plus rIFNα-2b for patients with COVID-19 in Zhejiang province.Methods:A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNα-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data.Results:The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2±4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0±5.0) d] ( t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] ( H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively ( Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8±3.9), (13.5±5.1) and (11.2±4.3) d, respectively( Z=6.722, P<0.05). Conclusions:The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNα-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy; and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.

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