Material basis and molecular mechanism of Angelicae Sinensis Radix in activating blood:based on computer-aided drug design / 中国中药杂志

Angelicae Sinensis Radix excels in activating blood, but the scientific mechanism has not been systematically analyzed, thus limiting the development of the medicinal. This study employed the computer-aided drug design methods, such as structural similarity-based target reverse prediction, complex network analysis, molecular docking, binding free energy calculation, cluster analysis, and ADMET(absorption, distribution, metabolism, excretion, toxicity) calculation, and enzyme activity assay in vitro, to explore the components and mechanism of Angelicae Sinensis Radix in activating blood. Target reverse prediction and complex network analysis yielded 40 potential anticoagulant targets of the medicinal. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis indicated that the targets mainly acted on the complement and coagulation cascade signaling pathway to exert the anticoagulant function. Among them, the key enzymes thrombin(THR) and coagulation factor Xa(FXa) in coagulation cascade and thrombosis were the drug targets for thromboembolic diseases. At the same time, molecular docking and cluster analysis showed that the medicinal had high selectivity for FXa. According to binding free energy score, 8 potential active components were selected for enzyme activity assay in vitro. The results demonstrated that 8 components inhibited THR and FXa, and the inhibition was stronger on FXa than on THR. The pharmacophore model of 8 active compounds was constructed, which suggested that the components had the common pharmacophore AAHH. The ADMET calculation result indicated that they had good pharmacokinetic properties and were safe. Based on target reverse prediction, complex network analysis, molecular docking and binding free energy calculation, anticoagulant activity in vitro, spatial binding conformation of molecules and targets, pharmacophore model construction, and ADMET calculation, this study preliminarily clarified the material basis and molecular mechanism of Angelicae Sinensis Radix in activating blood from the perspective of big data, and calculated the pharmacology and toxicology parameters of the active components. Our study, for the first time, revealed that the medicinal had obvious selectivity and pertinence for different coagulation proteins, reflecting the unique effect of different Chinese medicinals and the biological basis. Therefore, this study can provide clues for precision application of Angelicae Sinensis Radix and the development of the blood-activating components with modern technology.

Analysis of in vitro activity and compatibility of Dunhuang Yifang Dabupi Decoction on gastric cancer based on computer-aided drug design / 药学学报

Based on the research system of computer-aided drug design combined with complex network analysis, the potential mechanism of Dunhuang Dabupi Decoction in preventing and treating gastric cancer (GC) is analyzed, and the scientific connotation of its prescription rules is explored through the efficacy grouping. To study the effect of Dabupi Decoction freeze-dried powder solution on the proliferation activity of gastric cancer cells through cell experiments; the TCMSP and TCMID databases were used to collect the compound components of Dabupi Decoction. Swiss Target Prediction is used to predict potential targets of compounds. DrugBank, GeneCards, TTD, and DisGeNET were used to collect potential targets for gastric cancer. Analyze protein interactions of potential targets through the STRING database. DAVID database was used for KEGG enrichment analysis; Dabupi Decoction was divided into Wenzhong group (dried ginger), Yiqi group (ginseng, licorice, Atractylodes macrocephala), nourishing Yin group (Ophiopogon japonicus, Schisandra) and Jiangni group according to its efficacy characteristics. The inverse group (inula) has 4 functional compatibility groups. Cytoscape was used to construct a network of "medicinal flavor-potential active ingredient-key target" respectively, and the network was used to analyze the scientific connotation of the compatibility of efficacy groups. The Schrödinger software was used to verify the molecular docking of the core components and the core targets. The material basis of the Dabupi Decoction to prevent and treat gastric cancer was discovered through the combination of pattern analysis and combined free energy calculation. The core drug was analyzed from the perspective of dynamics through molecular dynamics simulation. Potential targets and representative potential compounds interact with each other. Cell experiments confirmed that Dabupitang freeze-dried powder solution can down-regulate the mitochondrial membrane potential of AGS gastric cancer cells, block the cell cycle in the G0/G1 phase (P < 0.05), and inhibit its proliferation (P < 0.05). The pathways enriched by the four functional groups contained in Dabupi Decoction are mainly distributed in the body's energy metabolism, inflammation-immune system regulation, and cycle-apoptotic functions. Each module is connected by a common target gene and has its own focus. The results of molecular docking showed that the compounds liquiritigenin, quercetin, kaempferol, isorhamnetin, methylophiopogonanone A, etc. may be the effective multi-target components of Dabupi Decoction. Estrogen receptor 1, androgen receptor, ATP-binding cassette superfamily G member 2, epidermal growth factor receptor, glycogen synthase kinase-3 beta and other targets have good affinity with each potential active compound, which may be a potential target of Dabupi Decoction for preventing and treating gastric cancer. Among them, kaempferol and the drug target EGFR not only have good binding ability, but also have good binding stability. This study is based on computer-aided drug design combined with complex network analysis strategies to initially reveal the material basis and molecular mechanism of Dabupi Decoction in the prevention and treatment of gastric cancer. It also explores the scientific connotation of Dabupi Decoction in the prevention and treatment of gastric cancer with different efficacy groups, and its clinical application provide chemical bioinformatics basis.

Bioinformatics screening and analysis of key differentially expressed genes characteristics in nonalcoholic fatty liver disease / 中华肝脏病杂志

Objective: To screen and analyze the key differentially expressed genes characteristics in nonalcoholic fatty liver disease (NAFLD) with bioinformatics method. Methods: NAFLD-related expression matrix GSE89632 was downloaded from the GEO database. Limma package was used to screen differentially expressed genes (DEGs) in healthy, steatosis (SS), and nonalcoholic steatohepatitis (NASH) samples. WGCNA was used to analyze the output gene module. The intersection of module genes and differential genes was used to determine the differential genes characteristic, and then GO function and KEGG signaling pathway enrichment analysis were performed. The protein-protein interaction network (PPI) was constructed using the online website STRING and Cytoscape software, and the key (Hub) genes were screened. Finally, R software was used to analyze the receiver operating characteristic curve (ROC) of the Hub gene. Results: 92 differentially expressed genes characteristic were obtained through screening, which were mainly enriched in inflammatory response-related functions of "lipopolysaccharide response and molecular response of bacterial origin", as well as cancer signaling pathways of "proteoglycan in cancer" and "T-cell leukemia virus infection-related". 10 hub genes (FOS, CXCL8, SERPINE1, CYR61, THBS1, FOSL1, CCL2, MYC, SOCS3 and ATF3) had good diagnostic value. Conclusion: The differentially expressed hub genes among the 10 NAFLD disease-related characteristics obtained with bioinformatics analysis may become a diagnostic and prognostic marker and potential therapeutic target for NAFLD. However, further basic and clinical studies are needed to validate.

Changes in choroidal thickness and axial length in adolescents with myopic anisometropia after orthokeratology treatment / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the changes of choroidal thickness(CT)and axial length(AL)in adolescents with myopic anisometropia before and after orthokeratology(OK lenses)treatment.METHODS: In this retrospective case-control study, 71 myopic participants who insisted on using OK lenses more than 6mo at night from June 2020 to September 2021 in Second People's Hospital of Shenzhen were enrolled. They were divided into three groups, including group A consisted of 31 myopic participants with non-anisometropic myopia with binocular lenses(A1 group: the right eyes, A2 group: the left eyes), group B consisted of 18 bilateral myopic anisometropes(B1 group: the eyes with high degree, B2: the eyes with low degree)and group C consisted of 22 unilateral myopic anisometropes(C1: the eyes with high degree, C2: the eyes with low degree). The length of axis, the CT values of subfoveal(SF)and the superior(S0.5, S1.0, S1.5), inferior(I0.5, I1.0, I1.5), temporal(T0.5, T1.0, T1.5)and nasal(N0.5, N1.0, N1.5)at 0.5, 1.0 and 1.5mm from the fovea before and after wearing lenses at 6mo were measured.RESULTS: After wearing lenses at 6mo, CT of all sites in group A1 was all thickening compared with that before wearing lenses(all P&#x003C;0.05), CT of all sites in group A2 was all thickening compared with that before wearing lenses, there was no difference compared with that before wearing lenses except for the SF, S1.5, T0.5 and T1.5 sites of the CT, the rest of the sites were different before and after wearing lenses(all P&#x003C;0.05), CT of T1.0, N1.5 and S1.5 sites in B1 group was thicker than that before wearing lenses(all P&#x003C;0.05), there was no difference in CT of all sites of the patients in group B2 before and after wearing lenses(all P&#x003E;0.05). Among them, the CT at SF, S0.5, S1.0, S1.5, I0.5, I1.0, I1.5, N0.5, N1.0 and N1.5 was thinner than before wearing lenses, but it was not statistically significant. There were differences in all sites of CT in group C1 compared with that before and after wearing lenses(all P&#x003C;0.05), for the CT of group C2, all the other sites except the points T1.5 and S1.5 was significantly thickened compared with that before wearing lenses(P&#x003C;0.05). The axis of patients in group B2 increased by 0.12±0.14mm after wearing lenses at 6mo compared with that before wearing lenses(all P&#x003C;0.001). The axis of group C2 increased by 0.20±0.17mm after wearing lenses at 6mo compared with that before wearing lenses(all P&#x003C;0.001). The interocular axial difference in group B and C decreased from 0.54±0.27, 0.88±0.39mm before wearing lenses to 0.47±0.20, 0.62±0.39mm after wearing lenses at 6mo(all P&#x003C;0.05). There was no significant in the interocular axis difference of group A1 and A2 before and after wearing lenses(P&#x003E;0.05).CONCLUSION: For adolescents with myopic anisometropia patients after long-term wearing OK lenses have CT thickening in high degree eyes, but no thickening in low-degree eyes, and even thinning. At the same time, wearing OK lenses can slow axis elongation and reduce interocular anisometropia difference in axis, which is an effective clinical method to control the development of anisometropia.

Abivertinib inhibits megakaryocyte differentiation and platelet biogenesis / 医学前沿

Abivertinib, a third-generation tyrosine kinase inhibitor, is originally designed to target epidermal growth factor receptor (EGFR)-activating mutations. Previous studies have shown that abivertinib has promising antitumor activity and a well-tolerated safety profile in patients with non-small-cell lung cancer. However, abivertinib also exhibited high inhibitory activity against Bruton's tyrosine kinase and Janus kinase 3. Given that these kinases play some roles in the progression of megakaryopoiesis, we speculate that abivertinib can affect megakaryocyte (MK) differentiation and platelet biogenesis. We treated cord blood CD34+ hematopoietic stem cells, Meg-01 cells, and C57BL/6 mice with abivertinib and observed megakaryopoiesis to determine the biological effect of abivertinib on MK differentiation and platelet biogenesis. Our in vitro results showed that abivertinib impaired the CFU-MK formation, proliferation of CD34+ HSC-derived MK progenitor cells, and differentiation and functions of MKs and inhibited Meg-01-derived MK differentiation. These results suggested that megakaryopoiesis was inhibited by abivertinib. We also demonstrated in vivo that abivertinib decreased the number of MKs in bone marrow and platelet counts in mice, which suggested that thrombopoiesis was also inhibited. Thus, these preclinical data collectively suggested that abivertinib could inhibit MK differentiation and platelet biogenesis and might be an agent for thrombocythemia.

Clinical prediction model of moderate and severe obstructive sleep apnea hypopnea in snoring patients / 中国医师进修杂志

Objective:To establish a simple and efficient clinical prediction model of moderate and severe obstructive sleep apnea hypopnea (OSAHS) in snoring patients based on the clinical data and morphological measurement data in order to increase the early diagnosis and then early intervention of OSAHS. The prediction model is evaluated by external validation.Methods:A total of 299 subjects from January 2015 to December 2018 were selected to perform polysomngraphy (PSG) in Yangpu Hospital, Tongji University School of Medicine. According to the PSG results, they were divided into moderate and severe OSAHS groups (143 cases) and control groups (156 cases). Clinical complications data and morphological measurement data were collected. The regression equation and ROC curve were established according to the Logistic regression method. Then, another 110 subjects from January 2019 to October 2019 were chosen as verified data group, and used to verify the accuracy of the prediction model. The data of 110 subjects were put into the equation according to risk factors and assignment. The ROC curve was drawn and the area under the curve was calculated. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value were calculated.Results:The predicted equation was: y = -10.707 86+0.589 60 × sex+ 0.141 61 × BMI+ 1.281 62 × tonsil size degree+ 1.807 43 × modified Mallampati degree′tongue position. The AUC of the ROC curve of prediction model in training set was 0.851(95% CI 0.807-0.895), the sensitivity was 83.9%, the specificity was 79.5%, and the cut-off value was 0.634.The AUC of the ROC curve in validation set was 0.827(95% CI 0.751-0.904) with a sensitivity of 73.3% and a specificity of 86.0%, and an accuracy of 79.1%. Its positive predictive value was 5.238, and negative predictive value was 0.310. Conclusions:The predictive model constructed by the combination of clinically accessible data (sex) and morphological measurement (BMI, tonsil size degree, modifiedMallampatidegree) has a relatively high predictive efficiency for screening snoring patients with moderate and severe OSAHS. The predictive model is proved with good forecast accuracy by the external verification method.

Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study / 中华医学杂志(英文版)

BACKGROUND@#Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment.@*METHODS@#This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR.@*RESULTS@#A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities.@*CONCLUSION@#Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients.@*CLINICAL TRIAL REGISTRATION@#ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.

L-carnitine treatment attenuates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction

Background/Aims@#Accumulating evidence indicates that L-carnitine (LC) protects against multiorgan damage through its antioxidant properties and preservation of the mitochondria. Little information is available about the effects of LC on renal fibrosis. This study examined whether LC treatment would provide renoprotection in a rat model of unilateral ureteral obstruction (UUO) and in vitro. @*Methods@#Sprague-Dawley rats that underwent UUO were treated daily with LC for 7 or 14 days. The influence of LC on renal injury caused by UUO was evaluated by histopathology, and analysis of gene expression, oxidative stress, mitochondrial function, programmed cell death, and phosphatidylinositol 3-kinase (PI3K)/ AKT/forkhead box protein O 1a (FoxO1a) signaling. In addition, H2O2-exposed human kidney cells (HK-2) were treated with LC. @*Results@#LC treatment inhibited expression of proinflammatory and profibrotic cytokines, and was followed by a significant attenuation of tubulointerstitial inflammation and fibrosis. The increased oxidative stress caused by UUO was associated with mitochondrial dysfunction and excessive apoptosis and autophagy via PI3K/AKT/FoxO1a-dependent signaling, and this was abrogated by administration of LC. In H2O2-exposed HK-2 cells, LC decreased intracellular production of reactive oxygen species, and suppressed expression of profibrotic cytokines and reduced the number of apoptotic cells. @*Conclusions@#LC protects against the progression of tubulointerstitial fibrosis in an obstructed kidney.

Structure modification and antimicrobial activity of novel cationic melittin analogues / 药学学报

Melittin exhibits high antibacterial potency against drug-resistant bacteria. However, the clinical utility of melittin is limited by its serious hemolytic activity. Thus, the need for developing novel melittin analogues with high antimicrobial activity and low hemolytic activity has grown. We designed, synthesized, and evaluated 20 novel melittin analogues with varying hydrophobic, polar or positively charged amino acids. The results showed that 8 compounds had antimicrobial activity (MIC: 1-4 μg·mL-1) against gram-positive pathogens equal to or better than that of melittin, and 16 compounds had low hemolytic activity (HC50 ≥ 11.9 μg·mL-1). Compounds 13 (MIC: 2-4 μg·mL-1) and 15 (MIC: 1-2 μg·mL-1) showed equal or better antimicrobial activity against both susceptible and resistant strains of Staphylococcus aureus and Enterococcus faecium compared to melittin (MIC: 4 μg·mL-1). Compound 13 (HC50: 24.0 ± 4.3 μg·mL-1) displayed noticeably decreased hemolytic activity compared to melittin (HC50: 5.3 ± 0.4 μg·mL-1). This work established a base for further study on the structure-activity relationships and structure-toxicity relationships of melittin.

Effect of withdrawal time on postpartum liver function in pregnant women receiving tenofovir disoproxil fumarate therapy for blocking mother to child transmission of hepatitis B / 中华临床感染病杂志

Objective:To investigate the effect of withdrawal time on postpartum liver function in pregnant women receiving tenofovir disoproxil fumarate (TDF) therapy for blocking mother-to-child transmission of HBV.Methods:A prospective study was conducted in Hangzhou First People’s Hospital from June 2016 to August 2018. A total of 84 pregnant women with HBsAg and HBeAg positive were enrolled and divided into two groups according to simple randomized grouping method with 42 cases in each group. In group A TDF was withdrawn immediately after delivery and in group B TDF was withdrawn 12 weeks after delivery. Finally, 66 patients completed the follow-up for 24 weeks postpartum, 35 cases in group A and 31 cases in group B. All patients were administered TDF from week 24-28 of pregnancy. HBV DNA loads and ALT levels were regularly measured and compared. Multivariate logistic regression was used to explore the risk factors of postpartum ALT flare. SPSS 26.0 statistical software was used for statistical processing.Results:Compared with the baseline levels, the HBV DNA loads at 16 weeks postpartum had no significant changes in both groups( Z=-0.742 and -1.891, both P>0.05). Postpartum ALT flare was observed in 21 of the 66 patients, 9 cases (25.71%, 9/35) in group A, and 12 cases (38.71%, 12/31) in group B ( χ2=1.280, P>0.05); and there was no significant difference in the severity of postpartum ALT flare between the two groups ( χ2=0.527, P>0.05). Binary logistic regression analysis showed that increased ALT level during pregnancy was an independent risk factor of postpartum ALT flare ( OR=13.75, 95% CI 1.49-126.85, P<0.05). Conclusions:When TDF was used for preventing mother-to-child HBV transmission, withdrawal at different times after delivery had no effect on postpartum liver function. ALT flare during pregnancy is a risk factor for postpartum ALT flare, so TDF should be discontinued carefully and liver function should be closely monitored postpartum for such patients.

Closing doubly committed ventricular septal defect through a super minimal intercostal incision / 中华胸心血管外科杂志

Objective:Combined with the actual clinical situation, to introduce the application of invasive trans super minimal intercostal device closure in doubly committed ventricular septal defect(DCVSD).Methods:Between January 2017 and July 2020, 82 DCVSD children were recruited. Relevant data such as operation time, length of hospital stay, postoperative complications, etc. were analyzed, and the follow-up of the postoperative period was used to evaluate the effect of the operation.Results:Among them, 2 children’s puncture points were bleeding. Chest closure time was obviously extended. The total operation time of the remaining children was 24-72(47.54±12.06)min, among which the umbrella release time was 5-37(16.16±8.01)min, and the chest opening and closing time was 14-59(31.56±9.58) min. Pericardial effusion occurred in 2 patients after operation, and the discharge time was more than 2 weeks. The remaining children were hospitalized for 3-9(5.79±1.45)days after surgery.Conclusion:Closing DCVSDs through a super minimal intercostal incision under TEE guidance was safe, effective and less trauma.

Nicotine exacerbates tacrolimus-induced renal injury by programmed cell death

Background/Aims@#Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal injury. @*Methods@#Sprague-Dawley rats were treated daily with NIC, TAC, or both drugs for 4 weeks. The influence of NIC on TAC-caused renal injury was examined via renal function, histopathology, oxidative stress, mitochondria, endoplasmic reticulum (ER) stress, and programmed cell death (apoptosis and autophagy). @*Results@#Both NIC and TAC significantly impaired renal function and histopathology, while combined NIC and TAC treatment aggravated these parameters beyond the effects of either alone. Increased oxidative stress, ER stress, mitochondrial dysfunction, proinf lammatory and profibrotic cytokine expressions, and programmed cell death from either NIC or TAC were also aggravated by the two combined. @*Conclusions@#Our observations suggest that NIC exacerbates chronic TAC nephrotoxicity, implying that smoking cessation may be beneficial for transplant smokers taking TAC.

Clinical efficacy of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer / 北京大学学报(医学版)

OBJECTIVE@#To observe the early efficacy and toxicity of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer (mCRPC).@*METHODS@#From May 2017 to July 2019, fifteen patients with mCRPC treated in Peking University First Hospital were collected. The median age was 70 years (43-77 years), and the pathological types were all adenocarcinoma, which was confirmed as distant metastasis by imaging examination. They were given the chemotherapy of docetaxel combined with carboplatin. The specific method was as follows: each cycle was 28 days. Androgen deprivation therapy was administered routinely throughout the treatment period. Blood routine, liver and kidney function, blood clotting function and prostate-specific antigen (PSA) tests were performed before each cycle. Docetaxel was administered intravenously on the first day of each cycle at a dose of 75 mg/m2, and carboplatin was administered intravenously on the second day at the dose calculated by Calvert formula. The main outcome measures including PSA decline range, pain remission rate and occurrence of adverse reactions were observed and analyzed.@*RESULTS@#Among the 15 patients, 12 had completed at least 4 cycles of chemotherapy and had short-term efficacy evaluation. PSA decline range > 50% was observed in 8 patients (66.7%). Among the 9 patients with bone pain, remarkable pain relief was observed in 4 patients (44.4%). Among the 4 patients with measurable metastatic lesions, 2 achieved partial response, 1 was evaluated as stable disease, and 1 was evaluated as progressive disease. The main adverse reactions of chemotherapy included bone marrow suppression, gastrointestinal reactions, fatigue and neurological disorders, and most of them were within the tolerable range.@*CONCLUSION@#This report is a case series study of docetaxel combined with carboplatin in the treatment of mCRPC reported in China and the conclusions are representative. The chemotherapy of docetaxel combined with carboplatin has positive short-term efficacy and high safety in patients with mCRPC, which is worthy of further promotion and exploration in clinical practice.

Composite bone and skin flap transplantation combined with bone lengthening for repairing lower limb burn with soft tissue and bone defect / 中国骨伤

OBJECTIVE@#To compare the effect of traditional fibula flap combined with allogeneic bone transplantation and composite bone flap transplantation combined with bone lengthening in staged repair of severe soft tissue and bone defect caused by lower limb burn.@*METHODS@#Total 68 patients with severe soft tissue and bone defect caused by lower limb burn from March 2015 to January 2018 were retrospectively analyzed, and they were divided into control group (34 cases) and study group (34 cases) according to the treatment plan. All patients had different degrees of soft tissue and bone tissue defects. In the study group, 34 patients were treated with composite bone flap transplantation combined with bone lengthening. There were 22 males and 12 females; the age ranged from 32 to 46(39.18±6.01) years; the time from injury to treatment was (16.69±5.11) h;28 cases were caused by explosion injury and 6 cases were caused by firearm burn; the length of bone defect was (12.10± 2.34) cm;and 16 cases were on the left side of affected limb 18 cases were on the right side. In the control group, there were 24 males and 10 females, aged 31 to 47 (38.93 ± 5.81) years;the time from injury to treatment was(17.10±5.63) h;the causes of injury were explosive injury in 30 cases and firearm burn in 4 cases; the length of bone defect was (11.96±2.51) cm;19 cases were on the left side and 15 cases on the right side. All patients were followed up for 6 months. The FMA scores before operation and 3 and 6 months after operation, treatment satisfaction, curative effect and complications of the two groups were recorded.@*RESULTS@#Limb function:there was no significant difference in FMA scores between the two groups before operation (@*CONCLUSION@#the combined use of composite bone flap transplantation and bone lengthening staged repair in the treatment of severe soft tissue and bone defect caused by lower limb burn can achieve good therapeutic effect, improve limb function, and have high treatment satisfaction and certain safety.

Preliminary exploration of the mechanism of Qingfei Paidu decoction against novel coronavirus pneumonia based on network pharmacology and molecular docking technology / 药学学报

Traditional Chinese medicine (TCM) network pharmacology and molecular docking technology were applied to explore the mechanism of anti-coronavirus pneumonia (coronavirus disease 2019, COVID-19) of Qingfei Paidu decoction. The Chinese Pharmacopoeia (2015 edition) and Traditional Chinese Medicine Systems Pharmacology (TCMSP), OMIM (Online Mendelian Inheritance in Man), GeneCard, STRING, and others online databases are used for building a series of network, and selecting the core target and analyzing the signal pathway. Finally, we make molecular docking predictions for the important compounds. The results showed that the Qingfei Paidu decoction compound-pneumonia target network contained 292 compounds and 214 corresponding targets, and the core targets involved AKT1 (AKT serine/threonine kinase 1), IL6 (interleukin 6), MAPK8 (mitogen-activated protein kinase 8), MAPK1 (mitogen-activated protein kinase 1), and JUN (jun proto-oncogene). GO (Gene Ontology) function enrichment analysis yielded 858 GO entries, and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment screening yielded 122 related pathways, including hypoxia inducible factor-1 (HIF-1) and Toll-like receptor (TLRs) signaling pathways related to pneumonia, as well as T-cell receptor (TCR) signaling pathway related to lung injury protection. The molecular docking results showed that some core compounds of the Chinese herbal medicine of Qingfei Paidu decoction have a certain degree of affinity for 2019-novel coronavirus (2019-nCoV) main protease (3C-like protease, 3CLpro) and angiotensin-converting enzyme 2 (ACE2). In this paper, we preliminarily explored the potential therapeutic mechanism for Qingfei Paidu decoction to against COVID-19 and predicted the active ingredients. We hope that the results will help to the further study on the active ingredients and mechanism of Qingfei Paidu decoction to COVID-19.

Pharmacological Analysis of Xuanfei Huazhuo Prescription in Treatment of Coronavirus Disease-2019 / 中国实验方剂学杂志

Objective:The targets and signaling pathways of Xuanfei Huazhuo prescription (XFHZP) for the treatment of coronavirus disease-2019 (COVID-19) were explored, and its possible action mechanisms were described through network pharmacology and basic analysis of modern pharmacology. Method:The compounds and targets in XFHZP were collected through TCMSP and BATMAN-TCM databases. The targets of COVID-19 were studied by GeneCards, NCBI and CTD databases. The PPI network was constructed through STRING database. The networks of "herb-meridian" and "traditional Chinese medicines-compounds-targets-disease" were generated by Cytoscape 3.7.0. Then, Kyoto Encyclopedia of Genes and Genomes（KEGG） analysis and Gene Ontology（GO） analysis were made for shared targets through the Omicshare platform. In addition, the disease targets of multiple organ injury, immune injury and severe acute respiratory syndrome (SARS) were retrieved and then mapped with XFHZP. The ratio of intersection targets to XFHZP's targets was calculated. Result:XFHZP has 10 traditional Chinese medicines in total, including 6 medicines with the meridian tropism to lung, 5 medicines with the meridian tropism to the spleen and 5 medicines with the meridian tropism to the stomach. There were 409 compounds and 2 271 targets. There were 8 same inflammatory factors in targets between XFHZP and COVID-19, and each inflammatory factor corresponded to multiple compounds. XFHZP and COVID-19 had 135 intersection targets, and 36 key targets were screened out. A total of 172 signaling pathways were screened out through KEGG signal pathway enrichment (P<0.05). There were 4 000 biological processes, 254 cell components, and 408 molecular functions (P<0.05) according to GO analysis. XFHZP had many common targets with various organ damage targets and immune damage targets, with the ratio of about 7.6%-97.8%. XFHZP had 173 intersection targets with SARS. Conclusion:XFHZP may treat COVID-19 through anti-inflammatory, organ protecting and immune effects. It will provide a certain theoretical basis for the development of drugs for COVID-19.

Material Basis of Xuanfei Huazhuo Prescription in Treatment of COVID-19 by Multi-target Molecular Docking / 中国实验方剂学杂志

Objective:Structure-based angiotension converting enzyme 2 (ACE2) and interleukin-6R (IL-6R) were taken as the target proteins to in the investigation of the material basis of Xuanfei Huazhuo prescription in the treatment of coronavirus disease-2019 (COVID-19) by molecular docking. Method:The compounds in Xuanfei Huazhuo prescription were retrieved through TCMSP. Structure-based ACE2 and IL-6R were taken as the target proteins to screen out the compounds with a better activity by molecular docking, and analyze structural properties of these compounds. Furthermore, the potential molecular mechanism of Xuanfei Huazhuo prescription in the treatment of COVID-19 was analyzed by target reverse prediction. Result:There were 312 potentially active compounds in Xuanfei Huazhuo prescription, including 75 highly active compounds and 15 highly active compounds for ACE2. There were 100 eligible active compounds and 3 highly active compounds for IL-6R, most of which belong to flavonoids. The herb-component-target network included 10 herbs, 126 compounds and 130 targets. String analysis showed that PIK3R1, SRC, AKT1, AR and EGFR might be the key targets of Xuanfei Huazhuo prescription. Conclusion:Based on the virtual screening of multi-target molecular docking, the anti-virus and anti-inflammatory material basis of Xuanfei Huazhuo prescription was preliminarily obtained. At the same time, based on the reverse prediction and analysis, potential targets and molecular mechanism of the recipe in the treatment of COVID-19 were explored, so as to provide clues for the multi-angle mining of Xuanfei Huazhuo prescription and its relevant prescriptions and the modernization development of monomer components.

Clinical Efficacy of Xuanfei Huazhuo Prescription on 40 Cases of COVID-19 / 中国实验方剂学杂志

Objective:To evaluate the clinical efficacy of Xuanfei Huazhuo prescription in the treatment of coronavirus disease-2019 (COVID-19). Method:A total of 40 patients with COVID-19 were selected and treated with Xuanfei Huazhuo prescription. The changes of body temperature, clinical symptoms, computed tomography (CT), blood routine and biochemical indexes were observed before and after treatment. Result:The 40 patients included 15 males and 25 females, with a male to female ratio of 1∶1.7. They were aged between 20-94 years old, with the average age of （43.9±16.3） years old. The course of disease was 8-23 days, with the average of （14±4.4） days. Compared with before administration, the patients' clinical symptoms, such as cough, fever, sputum, diarrhea, loss of appetite and fatigue, were all improved (P<0.05). Before treatment the traditional Chinese medicine (TCM) syndromes of patients were mainly cold dampness lung (57.5%) and cold dampness Lung (42.5%), and the tongue coating was mainly white greasy coating (52.9%). After adjuvant treatment with Xuanfei Huazhuo prescription, the fever removal time was (2.48±2.56) days; white blood cell (WBC), lymphocyte percentage (LYM%), neutrophil percentage (NEUT%), absolute value of lymphocytes (LYM #) indexes of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), total bilirubin (TBIL), ratio of glutamic oxaloacetic transaminase to glutamic pyruvic transaminase (AST/ALT) and lactate dehydrogenase (LDH) were basically restored to the normal range (P<0.05) compared with before administration. After adjuvant treatment with Xuanfei Huazhuo prescription, the results of three pharyngeal test virus nucleic acid tests were negative, and the lung CT showed that infected lesions were absorbed and all met the discharge criteria. All 40 patients met the discharge criteria and were all cured and discharged, with a cure rate of 100%. There has been no case of recurrence with a positive result of nucleic acid detection so far. The score of symptom and clinical index of patients after administration was （1.62±1.90）, which was significantly lower than that before administration (7.65±4.08, P<0.05). Conclusion:In the adjuvant treatment of COVID-19, Xuanfei Huazhuo prescription can reduce body temperature, promote the absorption of pulmonary inflammation, and improve clinical symptoms, such as fever and cough.

Effect of M1/M2 Alveolar Macrophage Subsets in COVID-19 and Regulatory Mechanism of Traditional Chinese Medicine / 中国实验方剂学杂志

The pathological anatomical results of coronavirus disease-2019 (COVID-19) patients showed that excessive inflammatory reaction in the lungs is one of the important causes for such complications as acute lung injury or acute respiratory distress syndrome. Therefore, regulation of immune response may be an effective measure for COVID-19. Alveolar macrophages have a high heterogeneity and plasticity. The dynamic changes of subsets balance and function of M1/M2 alveolar macrophages have a significant effect on pulmonary inflammatory response during the early and late stages of infection. This paper reviews the classification and function of macrophages and explores the mechanism of alveolar macrophage in the pathological process of COVID-19 at different stages and the pharmacodynamic mechanism of traditional Chinese medicine. Besides, it provides ideas for the treatment of COVID-19 with traditional Chinese medicine and other drugs' research and development based on the regulation of macrophage polarization.

Diagnosis and rational approach to emergency vascular surgery in the shadow of corona virus disease 2019 / 中华普通外科杂志

Objective:To explore a safe, effective and rapid rescue method and key points for the management of vascular surgical emergencies in an area under guarantine against COVID-19(corona virus disease 2019).Methods:Under the guidance of COVID-19 diagnosis and treatment guidelines , 4 cases of vascular surgical emergency patients admitted to our department from Feb 1 to Feb 10, 2020 were screened for COVID-19 and given emergency vascular surgical treatment.Results:Two patients had acute thoracic aortic dissection, one patient had acute left foot ulcer with infection, one patient had severe carotid artery stenosis and frequent TIA. All patients were diagnosed quickly according to the three-level triage process. Endovascular repair(TEVAR) was performed in 2 cases, carotid stenting in 1 case, and left foot amputation in 1 case. Two patients running postoperative fever below 38.5℃ were safely excluded out of COVID-19 and Cured. There were no other major morbidities nor mortality.Conclusions:Under the COVID-19 prevention and control guidelines, the establishing of a comprehensive prevention and control system of patient-medicine-care-management helps to perform confine operation on vascular surgical emergency.