1.The Development of Chinese Herbal Formulae for Non-severe COVID-19 Based on Artificial Intelligence Technology and Investigation of Its Action Mechanisms
Wenting HUANG ; Liansheng QIAO ; Di YAN ; Tengwen LIU ; Hongmei CAO ; Hongyan GUO ; Zhi ZHANG ; Jing CHENG ; Lan XIE ; Qingquan LIU
Journal of Traditional Chinese Medicine 2024;65(1):103-112
ObjectiveTo develop traditional Chinese medicine (TCM) formulae for the treatment of nonsevere coronavirus disease 2019 (COVID-19) and to explore its anti-inflammatory mechanism. MethodsThe dysregulated signaling pathways were determined in macrophages from bronchoalveolar lavage fluid of COVID-19 patients and in lung epithelial cells infected with SARS-CoV-2 in vitro based on transcriptome analysis. A total of 102 TCM formulae for the clinical treatment of nonsevere COVID-19 were collected through literature. The pathway-reversing rates of these formulae in macrophages and lung epithelial cells were evaluated based on signature signaling pathways, and the basic formula was determined in conjunction with TCM theory. The commonly used Chinese materia medica for nonsevere COVID-19 were summarized from the 102 TCM formulae as abovementioned. And together with the screening results from the Pharmacopoeia of the People's Republic of China, a “Chinese materia medica pool” was esta-blished for the development of TCM formulae for COVID-19. The regulatory effects of each herb on signaling pathways were obtained based on targeted transcriptome analysis. Oriented at reversing dysregulated signaling pathways of COVID-19, the calculation was carried out, and the artificial intelligent methods for compositing formulae, that are exhaustive method and parallel computing, were used to obtain candidate compound formulas. Finally, with reference to professional experience, an innovative formula for the treatment of nonsevere COVID-19 was developed. The ethanol extract of the formula was evaluated for its anti-inflammatory effects by detecting the mRNA expression of interleukin 1b (Il1b), C-X-C motif chemokine ligand 2 (Cxcl2), C-X-C motif chemokine ligand 10 (Cxcl10), C-C motif chemokine ligand 2 (Ccl2), nitric oxide synthase 2 (Nos2), and prostaglandin-endoperoxide synthase 2 (Ptgs2) using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in RAW264.7 cells treated with lipopolysaccharide (LPS). ResultsIn macrophages and lung epithelial cells, 34 dysregulated signaling pathways associated with COVID-19 were identified respectively. The effects of the 102 formulae for clinical treatment of nonsevere COVID-19 were evaluated based on the dysregulated signaling pathways and targeted transcriptome, and the result showed that Yinqiao Powder and Pingwei Powder (银翘散合平胃散, YQPWP) ranked first, reversing 91.18% of the dysregulated signaling pathways in macrophages and 100% of the dysregulated signaling pathways in lung epithelial cells. Additionally, YQPWP had the function of scattering wind and clearing heat, resolving toxins and removing dampness in accordance with the pathogenesis of wind-heat with dampness in COVID-19. It was selected as the basic formula, and was further modified and optimized to develop an innovative fomula Qiaobang Zhupi Yin (翘蒡术皮饮, QBZPY) based on expert experience and artificial intelligence in composing formulae. QBZPY can reverse all the dysregulated signaling pathways associated with COVID-19 in macrophages and lung epithelial cells, with the reversing rates of 100%. The chief medicinal of QBZPY, including Lianqiao (Fructus Forsythiae), Xixiancao (Herba Siegesbeckiae) and Niubangzi (Fructus Arctii), can down-regulate multiple signaling pathways related with virus infection, immune response, and epithelial damage. RT-qPCR results indicated that compared with the model group, the QBZPY group down-regulated the mRNA expression of Il1b, tumor necrosis factor (Tnf), Cxcl2, Cxcl10, Ccl2, Nos2 and Ptgs2 induced by LPS in RAW264.7 cells (P<0.05 or P<0.01). ConclusionBased on targeted transcriptome analysis, expert experience in TCM and artificial intelligence, QBZPY has been developed for the treatment of nonsevere COVID-19. The ethanol extract of QBZPY has been found to inhibit mRNA expression of several pro-inflammatory genes in a cellular inflammation model.
2.Therapeutic effect and mechanism of astragalus on acute respiratory distress syndrome in sepsis mice
Yanxiang HA ; Po HUANG ; Rui ZHANG ; Chunxia ZHAO ; Xiaolong XU ; Yuhong GUO ; Shuo WANG ; Qingquan LIU
Chinese Journal of Emergency Medicine 2024;33(10):1407-1412
Objective:To verify the therapeutic effect of Astragalus on mice with acute respiratory distress syndrome with sepsis and to explore its mechanism.Methods:Seventy SPF-grade C57 mice were divided into astragalus group ( n=30), control group ( n=30) and sham surgery group ( n=10) according to random number table method, and CLP surgery was performed on Astragalus group and control group to induce sepsis acute respiratory distress syndrome, and CLP sham surgery was performed in the sham surgery group. After surgery, the astragalus group was treated with astragalus decoction for gastric gavage, the sham surgery group and the control group were gavaged with normal saline, and the mice were sacrificed 12 hours and 24 hours after the operation, and the lung histopathology was observed, the ratio of dry to wet weight of lung tissue, the protein concentration of alveolar lavage fluid was determined, the alveolar lavage fluid and serum were analyzed proteomics, and the differential proteins were enriched and analyzed. Results:Astragalus reduced the total protein concentration of BALF in ARDS mice, reduced the dry-to-wet ratio of ARDS mice, and HE staining of lung tissues showed that Astragalus decoction improved acute alveolar injury in ARDS mice. Proteomic analysis of serum samples and BALF samples showed that there were certain differential proteins between astragalus group and control group, and enrichment analysis showed that it was mainly enriched in the pathway of inflammatory factors, confirming that astragalus decoction may play a role by inhibiting the activation and release of inflammatory factors.Conclusions:Astragalus decoction can effectively reduce the inflammatory exudation of lung tissue in acute respiratory distress syndrome of sepsis, and its mechanism of action may be to inhibit the expression of inflammatory factors.
3.Animal experimental study of 5G remote robot-assisted thoracoscopic lobectomy
Yu TIAN ; Jia HUANG ; Jiantao LI ; Long JIANG ; Hongda ZHU ; Qingquan LUO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(08):1112-1115
Objective To explore the feasibility of 5G remote robot-assisted pulmonary lobectomy through animal experiments. Methods In this research, the Toumai® surgical robot was manipulated remotely by the surgeon in the Control Center of the MedBot Company through the 5G network established by China Telecom, and the experimental pig underwent lobectomy in simulated operating room. Results The animal experiment surgery was successfully completed. The surgeon remotely manipulated the surgical robot to complete the lobectomy of right apical lobe and mediastinal lymph node dissection. The entire animal experiment took about 60 minutes, with an average round-trip network delay of 125 (110-155) ms, and no network interruption or robot malfunction occurred. Conclusion This animal experiment is the first attempt of 5G remote thoracic surgery, which preliminarily proves the feasibility of completing remote lobectomy through the Toumai® surgical robot 5G wireless network connection. The systematic surgical procedure is summarized, which lays a foundation for the subsequent experiments and clinical applications of 5G remote robot-assisted thoracic surgery.
4.Effect of miR⁃26a⁃3p targeting Survivin on hypoxia/reoxygenation inj ury of H9c2 cardiomyocyte
Jiancheng Huang ; Hongying Li ; Qingquan Li ; Huijun Zhang ; Xiaobing Li
Acta Universitatis Medicinalis Anhui 2023;58(11):1934-1941
Objective :
To investigate the effects of miR⁃26a⁃3p on rat myocardial cell ( H9c2) injury induced by
hypoxia/reoxygenation (H/R) and its mechanism .
Methods :
H9c2 cardiomyocytes in logarithmic growth phase were subjected to hypoxia (1% O2 ) for 6 h , and reoxygenated at different times (2 , 4 , 8 , 12 h) to establish H/R model cell . Normoxia group was also set up , and cell proliferation activity was detected by cell counting kit⁃8 (CCK⁃8) . The level of lactic dehydrogenase (LDH) in cell supernatant was determined by colorimetry . The expression levels of miR⁃26a⁃3p and Survivin mRNA were detected by real⁃time fluorescence quantitative PCR (qRT⁃PCR) . The expression level of Survivin protein in the cells was detected by Western blot . H9c2 cells were transfected with miR⁃26a⁃3p inhibitor and negative control inhibitor NC , Survivin gene siRNA interference plasmid ( si⁃Survivin) and negative control si⁃NC , followed by H/R intervention . CCK⁃8 was used to detect cell proliferation in each group . The activity of superoxide dismutase (SOD) and the content of malonaldehyde (MDA) in cell and the level of LDH in supernatant were determined by colorimetry . The apoptosis level of each group was detected by flow cytometry . The protein expression levels of Bcl⁃2 associated X protein ( Bax) , B ⁃cell lymphoma⁃2 ( Bcl⁃2 ) , cleaved caspase⁃3 and Survivin were detected by Western blot . Targeting relationship between miR⁃26a⁃3p and Survivin gene was determined by dual luciferase .
Results :
Compared with the normoxia group , proliferative activity , mRNA and protein expression levels of Survivin in H9c2 cells gradually decreased with the extension of reoxygen ation time (P < 0. 05) , while LDH and expression level of miR⁃26a⁃3p gradually increased ( P < 0. 05) . Downregulating the expression of miR⁃26a⁃3p increased proliferative activity , SOD activity , and expression level of Bcl⁃2 protein in H9c2 cells exposed to H/R ( P < 0. 05) , while MDA content , LDH release amount , apoptosis rate , expression levels of Bax and cleaved caspase⁃3 protein decreased (P < 0. 05) . Survivin deficiency reversed the protective effect of miR⁃26a⁃3p inhibitor on H9c2 cells induced by H/R . Dual luciferase reporter gene assay confirmed that Survivin was the target gene of miR⁃93 ⁃5p .
Conclusion
miR⁃26a⁃3p is highly expressed in cardiomyocyte injury induced by H/R . Inhibition of miR⁃26a⁃3p expression can inhibit H/R⁃induced cardiomyocyte apoptosis and oxidative stress by targeted up⁃regulation of Survivin expression .
5.Right upper lobe resection assisted by Toumai® endoscopic surgery robot in two patients
Jia HUANG ; Yu TIAN ; Peiji LU ; Long JIANG ; Jiantao LI ; Hongda ZHU ; Hao LIN ; Qingquan LUO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2022;29(04):519-523
Objective To analyze the efficacy and safety of Toumai® endoscopic surgery robot in right upper lobe resection. Methods The clinical data of 2 patients with non-small cell lung cancer who received right upper lobe resection with Toumai® endoscopic surgery robot in Shanghai Chest Hospital, Shanghai Jiao Tong University in November 2021 were retrospectively analyzed. Both patients were male, aged 66 years and 44 years, respectively. Results The operation was successful in both patients with no conversion to thoracotomy, surgical complication or death. The operation time was 65 min and 48 min, and the amount of intraoperative bleeding was 80 mL and 50 mL, respectively. The postoperative hospital stay was 3 days. There was no blood transfusion during the perioperative period. Conclusion The application of Toumai® endoscopic surgery robot in lobectomy is preliminarily proved to be safe and effective. Compared with Da Vinci robotic surgery system, it has similar clear 3D vision and flexible and stable operation, which can become one of the important choices for the new generation of minimally invasive chest surgery.
6.Validation of the Chinese version of ureteral stent symptom questionnaire
Kai MA ; Xingke QU ; Qingquan XU ; Liulin XIONG ; Xiongjun YE ; Lizhe AN ; Weinan CHEN ; Xiaobo HUANG
Chinese Journal of General Practitioners 2021;20(5):587-593
Objectives:To validate the Chinese version of the Ureteral Stent Symptoms Questionnaire(Chinese-USSQ) in patients with an indwelling ureteral stent.Methods:The original USSQ was translated into Chinese and linguistically validated following the cross-cultural adaptation of health-related quality of life measures.A total of 83 patients (cases) with indwelling ureteral stent and 90 healthy subjects (controls) were asked to complete the Chinese-USSQ as well as European Quality of Life Visual Analogue scale(EQ-VAS)(for both genders), the International Prostate Symptom Scale (IPSS) (for male), and Urogenital Distress Inventory-6 (for female). Patients were evaluated at weeks 1 and 4 after stent placement and at week 4 after removal. The psychometric properties of the questionnaire were analyzed.Results:The Chinese version of USSQ include 43 items, which addressed various domains of health(6 sections) covering urinary symptoms, pain, general health, work performance and sexual matters with additional problems. A total of 78 patients(45 males and 33 females) and 90 controls (41 males and 49 females)were included for analysis. Internal consistencies (Cronbach′s α coefficients: 0.60-0.78) and test-retest reliability (Spearman correlation coefficient: 0.69-0.91) were satisfactory for urinary symptom, body pain, general health, and work performance domains. Most USSQ domains showed moderate correlations with each other. The convergent validity determined by correlation between other instruments and corresponding USSQ domain was satisfactory. At week 4 it was moderate for the urinary symptoms index compared to the IPSS in men(Spearman correlation coefficient>0.60), for the urinalry symptoms index compared to the UDI-6 score in women(Spearman correlation coefficient 0.52).Sensitivity to change and discriminant validity were also good in most domains ( P<0.01). Only a small proportion of the study population had an active sexual life with the stent in situ, which limited its analysis. Only 1(1.3%) and 6(7.7%) patients had an active sex life at week 1 and 4 after stent placement; meanwhile, 34(43.6%) patents were sexually active at week 4 after stent removal. Conclusion:The Chinese version of the USSQ is a reliable and valid instrument that can be used for Chinese patients with a indwelling ureteral stent in the clinical and research settings.
7.Simultaneous Determination of 6 Flavonoids in Zhuang Medicine Engelhardia roxburghiana by HPLC-QAMS and Multivariate Statistical Analysis
Xia YAN ; Xueyan ZHU ; Songhua HE ; Hui ZHANG ; Yi LUO ; Qingquan HUANG
China Pharmacy 2021;32(20):2485-2491
OBJECTIVE:To establish a m ethod for simultaneous determination of neoastilbin ,astilbin,neoisoastilbin,isoastilbin, quercitrin and engeletin in Engelhardia roxburghiana,and conduct multivariate statistical analysis. METHODS :HPLC-QAMS method was adopted. The determination was performed on Phenomenex SuperLu C 18 column with mobile phase consisted of acetonitrile-0.1% formic acid (19 ∶ 81,V/V)at the flow rate of 1.0 mL/min. The detection wavelengths were set at 254 nm (neoastilbin,astilbin,neoisoastilbin,isoastilbin,engeletin)and 291 nm(quercitrin). The column temperature was 30 ℃,and sample size was 10 μL. Using astilbin as internal substance,and the relative correction factors of other 5 factors were calculated. The contents of each component were calculated according to relative correction factor ,and were compared with the results of external standard method. SPSS 22.0 software was used for cluster analysis and principal component analysis. RESULTS :The linear range of neoastilbin ,astilbin,neoisoastilbin,isoastilbin,quercitrin and engeletin were 0.007-0.311,0.871-18.184,0.002-0.119, 0.052-1.251,0.105-2.202,0.020-2.319 μg(r>0.999),respectively. RSDs of precision ,reproducibility and stability (24 h)tests were all lower than 3%. The average recoveries were 97.32%,94.89%,97.15%,96.90%,97.52% and 97.53%(RSDs were 1.09% -2.60% ,n=6),respectively. The relative correction factors of neoastilbin ,neoisoastilbin,isoastilbin,quercitrin and engeletin were 1.252 6,1.198 3,0.958 6,0.807 1 and 1.138 1, respectively. The contents of neoastilbin , neoisoastilbin, qq.com isoastilbin,quercitrin and engeletin measured by QAMS were 0.394 2-2.067 2,0.139 1-0.804 7,2.864 8-8.554 8,4.581 2- 11.371 1,1.028 9-13.401 5 mg/g;the contents of neoastilbin , astilbin,neoisoastilbin,isoastilbin,quercitrin and engeletin were 0.367 2-1.925 3,46.361 1-126.342 1,0.138 1-0.798 8,2.966 2-8.857 8, 4.642 5-11.523 3,0.970 6-12.641 9 mg/g,respectively. Relative errors of two methods was lower than or equal to 3.55%. The results of cluster analysis showed that 9 batches of samples could be clustered into two categories ;S8 sample was one category and others were one category. The results of principal component analysis showed that accumulative contribution rate of former 2 principle components was 84.745%,and the results of sample classification were consistent with those of cluster analysis. CONCLUSIONS : The established HPLC-QAMS method is accurate ,feasible and repeatable ,and can be used for simultaneous determination of 6 flavonoids in E. roxburghiana ,and it can provide reference for quality control.
8.Sample Retention Management and Evaluation in Drug Inspection Agencies Based on Process- oriented Adminis- tration Concept
Weimin ZHANG ; Qingquan HUANG ; Baobin HUANG
China Pharmacy 2021;32(3):257-261
OBJECTIVE:To combine with the concept of process-oriented administration ,and to provide reference for improving the process and measures of the sample retention management and evaluation in drug inspection agencies. METHODS : From the aspects of organizational management and control measures ,the improvement measures for sample retention management system were investigated. From the aspects of warehouse-in check ,storage management and warehouse-out judgment ,warehouse management and informatization ,the improvement measures for procedures and measures about sample retention management were explored. From the aspects of evaluation content and quality control measures ,the evaluation and continuous improvement of sample retention management were investigated. RESULTS & CONCLUSIONS :In the aspect of organizational management ,it is necessary to improve management procedures and processes ,determine sample retention objectives and plans ,improve post allocation and management ,and improve safety emergency plans. In the aspect of control measures ,it is necessary to improve the business management measures such as warehouse-in status inspection ,adjust the conditions such as warehouse space allocation , and improve the intelligent prompt of remaining validity period of samples. The key to the three links of warehouse-in ,storage and warehouse-out are warehouse-in check ,storage space and condition control ,and warehouse-out judgement. The relevant processes and measures can be improved from these aspects. The contents of sample retention management evaluation includes management system,management measures and process ,improvement and evaluation. Plan-Do-Check-Action (PDCA)cycle is a measure to improve the efficiency and quality of sample retention management in drug inspection agencies .
9.Upper urinary tract calculi complicating with emphysematous pyelonephritis: 5 cases report and literature review
Kai MA ; Bo YANG ; Xingke QU ; Qingquan XU ; Liulin XIONG ; Xiongjun YE ; Xiaobo HUANG
Chinese Journal of Urology 2020;41(4):277-281
Objective:To discuss the clinical manifestation, diagnosis and treatment of upper urinary tract calculi complicating with emphysematous pyelonephritis(EPN).Methods:The clinical data of 5 cases of upper urinary tract calculi complicating with EPN diagnosed in our department from July 2012 to December 2019 were retrospectively analyzed, and literatures were reviewed. 5 patients were identified by computed tomography scanning to upper urinary tract calculi complicating with EPN, 3 female and 2 male, aged 40-67 years, 2 staghorn calculi and 3 multiple stones. One patient suffered from diabetes mellitus. All cases presented with fever at the enrollment point, and the body temperature were 38.7℃, 38.8℃, 37.5℃, 38.6℃, 40.0℃, respectively. And the number of white blood cells and neutrophile granulocyte of these cases were higher than normal reference value, were 17.2×10 9/L, 0.90; 14.9×10 9/L, 0.89; 11.2×10 9/L, 0.85; 15.1×10 9/L, 0.87; 13.3×10 9/L, 0.88, respectively. The C-reactive protein were increased in all of the cases, especially in case 1(68 mg/l), case 2(253 mg/l), and case 5(67 mg/l). And 3 cases with renal insufficiency. Case 3 and case 4 were controlled the infection with medical management alone, and case 5 with percutaneous drainage plus medical management. The pyelonephritis of other 2 cases were uncontrolled, the body temperature of case 1 returned to normal after treated with percutaneous drainage of perirenal abscess plus nephrostomy plus medical management, but the imaging findings of kidney was not relief by CT scan after 4 weeks. Case 2 was persistent fever until treated with fluconazole according to the medicine sensitive experiment’s result of urine culture after undergoing nephrostomy plus indwelled a double J tube in ureter, but the CT findings of kidney grew worse 1 week later. Results:Of the 5 patients, 1 received first-stage nephrostomy and second-stage percutaneous nephrolithotomy, 2 received same session surgery, 2 received nephrectomy. There was no complications occurred except postoperative fever in 1 case. Postoperative pathology of the nephrectomy revealed glomerular sclerosis, glomerulus dilation, and inflammatory granulation tissue was formed. And 1-84 months follow-up showed no recurrence in all the cases.Conclusions:Upper urinary tract calculi complicating with EPN is an rare acute severe infection, CT is the best choice of early diagnosis, double J stenting or percutaneous drainage of abscess with broad-spectrum antibiotics could be the preferred treatment.
10.Perioperative outcomes of robot-assisted versus video-assisted right upper lobectomy in non-small cell lung cancer: A retrospective cohort study
Yu TIAN ; Jia HUANG ; Peiji LU ; Jiantao LI ; Hao LIN ; Long JIANG ; Tianxiang CHEN ; Qingquan LUO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2020;27(10):1134-1139
Objective To summarize the perioperative outcome of patients undergoing robot-assisted thoracic surgery (RATS) or four-port single-direction video-assisted thoracic surgery (VATS) right upper lobectomy (RUL), and to discuss the safety and the essentials of the surgery. Methods The clinical data of 579 patients with non-small cell lung cancer (NSCLC) undergoing minimally invasive RUL in Dr. Luo Qingquan’s team of our center from 2015 to 2018 were retrospectively analyzed. There were 246 males and 333 females aged 33-78 years. The 579 patients were divided into a RATS group (n=283) and a VATS group (n=296) according to surgical methods. Baseline characteristics and perioperative outcomes including dissected lymph nodes, postoperative duration of drainage, postoperative hospital stay, postoperative complications and surgery cost were compared between the two groups. Results There was no significant difference in baseline data between the two groups (P>0.05), and no postoperative 30 d mortality or intraoperative blood transfusion was observed. Compared with VATS, RATS had shorter operation time (90.22±12.16 min vs. 92.68±12.26 min, P=0.016), postoperative hospital stay (4.67±1.43 d vs. 5.31±1.59 d, P<0.001) and time of drainage (3.55±1.38 d vs. 4.16±1.58 d, P<0.001). No significant difference was observed between the two groups in the lymph nodes dissection, blood loss volume, conversion rate or complications. The cost of RATS was much higher than that of VATS (93 275.46±13 276.69 yuan vs. 67 082.58±12 978.17 yuan, P<0.001). Conclusion The safety and effectiveness of robot-assisted and video-assisted RUL are satisfactory, and they have similar perioperative outcomes. However, RATS costs relatively shorter operation time and postoperative hospital stay.


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