OBJECTIVE: To evaluate the effect and safety of Chinese medicine (CM) Fuzheng Huazhuo Decoction (FHD) in treating patients with coronavirus disease 2019 (COVID-19) who persistently tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This retrospective cohort study was conducted at Shanghai New International Expo Center shelter hospital in China between April 1 and May 30, 2022. Patients diagnosed as COVID-19 with persistently positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results for ⩾8 days after diagnosis were enrolled. Patients in the control group received conventional Western medicine (WM) treatment, while those in the FHD group received conventional WM plus FHD for at least 3 days. The primary outcome was viral clearance time. Secondary outcomes included negative conversion rate within 14 days, length of hospital stay, cycle threshold (Ct) values of the open reading frame 1ab (ORF1ab) and nucleocapsid protein (N) genes, and incidence of new-onset symptoms during hospitalization. Adverse events (AEs) that occurred during the study period were recorded. RESULTS: A total of 1,765 eligible patients were enrolled in this study (546 in the FHD group and 1,219 in the control group). Compared with the control group, patients receiving FHD treatment showed shorter viral clearance time for nucleic acids [hazard ratio (HR): 1.500, 95% confidence interval (CI): 1.353-1.664, P<0.001] and hospital stays (HR: 1.371, 95% CI: 1.238-1.519, P<0.001), and a higher negative conversion rate within 14 days (96.2% vs. 82.6%, P<0.001). The incidence of new-onset symptoms was 59.5% in the FHD group, similar to 57.8% in the control group (P>0.05). The Ct values of ORF1ab and N genes increased more rapidly over time in the FHD group than those in the control group post-randomization (ORF1ab gene: β =0.436±0.053, P<0.001; N gene: β =0.415 ±0.053, P<0.001). The incidence of AEs in the FHD group was lower than that in the control group (24.2% vs. 35.4%, P<0.001). No serious AEs were observed. CONCLUSION FHD was effective and safe for patients with persistently positive SARS-CoV-2 PCR tests. (Registration No. ChiCTR2200063956).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/virology* ; Adult ; Aged ; Treatment Outcome

OBJECTIVE: To assess the effect and safety of Reyanning Mixture (RYN) in treating asymptomatic or mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents. METHODS: This is a prospective, open-label, randomized controlled trial. Patients aged 1-17 years and diagnosed with asymptomatic or mild coronavirus disease-2019 (COVID-19) were assigned to an intervention group (RYN plus standard care) and a control group (standard care) according to a randomization list. The primary outcomes were SARS-CoV-2 negative conversion time. Secondary outcomes included negative conversion rate on days 3 and 7, hospital length of stay, symptom relief rate, new-onset symptoms of asymptomatic infected patients, and progressive disease rate. The cycle threshold (Ct) values of ORF1ab or N genes were also tested. RESULTS: A total of 214 patients in the intervention group and 217 in the control group were analyzed. The SARS-CoV-2 negative conversion time was significantly shortened in the intervention group [5 days (interquartile range (IQR): 5-6) vs. 7 days (IQR: 6-7), P<0.01]. By days 3 and 7, the negative conversion rates were significantly higher in the intervention group (day 3: 32.7% vs. 21.2%, P=0.007; day 7: 75.2% vs. 60.8%, P=0.001). Ct values significantly increase on day 2 [ORF1ab gene: 35.62 (IQR: 29.17-45.00) vs. 34.22 (IQR: 28.41-39.41), P=0.03; N gene: 34.97 (IQR: 28.50-45.00) vs. 33.51 (IQR: 27.70-38.25), P=0.024] and day 3 [ORF1ab gene: 38.00 (IQR: 32.72-45.00) vs. 35.81 (IQR: 29.96-45.00), P=0.003; N gene: 37.16 (IQR: 32.01-45.00) vs. 35.26 (IQR: 29.09-45.00), P=0.01]. No significant difference was found in hospital length of stay between the two groups (P>0.05). Symptoms of cough were significantly improved (82.2% vs. 70.0%, P=0.02) and wheezing was significantly reduced (0.7% vs. 12.9%, P<0.01) in the intervention group compared with the control group. During the trial, no disease progression or serious adverse events were reported. CONCLUSION Adding RYN to standard care may be a safe and effective treatment for children with asymptomatic and mild SARS-CoV-2 infection. (Registration No. ChiCTR2200060292).

OBJECTIVE: To evaluate the efficacy and safety of Huashi Baidu Granules (HSBD) in treating patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. METHODS: A single-center retrospective cohort study was conducted during COVID-19 Omicron epidemic in the Mobile Cabin Hospital of Shanghai New International Expo Center from April 1st to May 23rd, 2022. All COVID-19 patients with asymptomatic or mild infection were assigned to the treatment group (HSBD users) and the control group (non-HSBD users). After propensity score matching in a 1:1 ratio, 496 HSBD users of treatment group were matched by propensity score to 496 non-HSBD users. Patients in the treatment group were administrated HSBD (5 g/bag) orally for 1 bag twice a day for 7 consecutive days. Patients in the control group received standard care and routine treatment. The primary outcomes were the negative conversion time of nucleic acid and negative conversion rate at day 7. Secondary outcomes included the hospitalized days, the time of the first nucleic acid negative conversion, and new-onset symptoms in asymptomatic patients. Adverse events (AEs) that occurred during the study were recorded. Further subgroup analysis was conducted in vaccinated (378 HSBD users and 390 non-HSBD users) and unvaccinated patients (118 HSBD users and 106 non-HSBD users). RESULTS: The median negative conversion time of nucleic acid in the treatment group was significantly shortened than the control group [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The negative conversion rate of nucleic acid in the treatment group were significantly higher than those in the control group at day 7 (91.73% vs. 86.90%, P=0.014). Compared with the control group, the hospitalized days in the treatment group were significantly reduced [10 days (IQR: 8-11 days) vs. 11 days (IQR: 10.25-12 days); P<0.01]. The time of the first nucleic acid negative conversion had significant differences between the treatment and control groups [3 days (IQR: 2-4 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The incidence of new-onset symptoms including cough, pharyngalgia, expectoration and fever in the treatment group were lower than the control group (P<0.05 or P<0.01). In the vaccinated patients, the median negative conversion time and hospitalized days were significantly shorter than the control group after HSDB treatment [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days), P<0.01; 10 days (IQR: 8-11 days) vs. 11 days (IQR: 10-12 days), P<0.01]. In the unvaccinated patients, HSBD treatment efficiently shorten the median negative conversion time and hospitalized days [4 days (IQR: 2-6 days) vs. 5 days (IQR: 4-7 days), P<0.01; 10.5 days (IQR: 8.75-11 days) vs. 11.0 days (IQR: 10.75-13 days); P<0.01]. No serious AEs were reported during the study. CONCLUSION HSBD treatment significantly shortened the negative conversion time of nuclear acid, the length of hospitalization, and the time of the first nucleic acid negative conversion in patients infected with SARS-COV-2 Omicron variant (Trial registry No. ChiCTR2200060472).

OBJECTIVE: To evaluate the effectiveness and safety of Baidu Jieduan Granules (BDJDG) to treat common type coronavirus disease 2019 (COVID-19). METHODS: This multicenter, retrospective, and observational clinical trial included 230 common COVID-19 patients in Leishenshan, Huangshi, and Laohekou Hospitals in Wuhan from January 21 to March 26, 2020. The included patients were further divided into two subgroups according to the use of supplemental oxygen, mild and moderate groups. During the first 14 d of hospitalization, all patients were administered BDJDG combined with conventional Western medicine, and observed for continuous 28 d. Primary outcomes were disease progression rate and discharge rate. Secondary outcomes included negative conversion time of nucleic acid, hospitalization duration, clinical symptom subsidence time, and symptom regression rate. RESULTS: A total of 230 common COVID-19 patients were analyzed (138 in moderate group and 92 in mild group). By day 28, the disease progression rate was 4.3% and the discharge rate was 95.7%. All mild cases recovered and were discharged from hospital. The median negative conversion time of nucleic acid of all 230 COVID-19 patients was 12 d [inter-quartile range (IQR) 3.5-17], the median hospitalization duration was 15 d (IQR 12-20). The median time to fever, cough, and fatigue recovery was 4 d (IQR 2-6), 8 d (IQR 5-12), and 8 d (IQR 5-11). The recovery rate of fever, cough, and fatigue was 94.6%, 90.5%, and 93.5%. The median time to clinical improvement was 12 d (IQR 10-17). Compared with the baseline, total leukocyte counts, neutrophil counts, lymphocyte counts, and platelet counts were increased significantly on days 7 and 14 (P<0.01). C-reactive protein markedly increased on day 3 and significantly decreased on days 7 and 14 (P<0.01). No serious adverse events occurred during treatment. CONCLUSION BDJDG may be effective and safe for treatment of common type COVID-19. (Registration No. ChiCTR2000030836).
C-Reactive Protein ; China ; Cough/drug therapy* ; Disease Progression ; Fatigue ; Fever ; Humans ; Nucleic Acids ; Oxygen ; Retrospective Studies ; SARS-CoV-2 ; Treatment Outcome ; COVID-19 Drug Treatment

OBJECTIVE: Severe cases of coronavirus disease 2019 (COVID-19) are expected to have a worse prognosis than mild cases. Shenhuang Granule (SHG) has been shown to be a safe and effective treatment for severe COVID-19 in a previous randomized clinical trial, but the active chemical constituents and underlying mechanisms of action remain unknown. The goal of this study is to explore the chemical basis and mechanisms of SHG in the treatment of severe COVID-19, using network pharmacology. METHODS: Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was employed to screen chemical constituents of SHG. Putative therapeutic targets were predicted by searching traditional Chinese medicine system pharmacology database and analysis platform, SwissTargetPrediction, and Gene Expression Omnibus (GEO) databases. The target protein-protein interaction network and enrichment analysis were performed to investigate the hub genes and presumptive mechanisms. Molecular docking and molecular dynamics simulations were used to verify the stability and interaction between the key chemical constituents of SHG and COVID-19 protein targets. RESULTS: Forty-five chemical constituents of SHG were identified along with 131 corresponding therapeutic targets, including hub genes such as HSP90AA1, MMP9, CXCL8, PTGS2, IFNG, DNMT1, TYMS, MDM2, HDAC3 and ABCB1. Functional enrichment analysis indicated that SHG mainly acted on the neuroactive ligand-receptor interaction, calcium signaling pathway and cAMP signaling pathway. Molecular docking showed that the key constituents had a good affinity with the severe acute respiratory syndrome coronavirus 2 protein targets. Molecular dynamics simulations indicated that ginsenoside Rg4 formed a stable protein-ligand complex with helicase. CONCLUSION Multiple components of SHG regulated multiple targets to inhibit virus invasion and cytokine storm through several signaling pathways; this provides a scientific basis for clinical applications and further experiments.
Humans ; Molecular Docking Simulation ; Ligands ; Network Pharmacology ; Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional ; COVID-19 Drug Treatment

Objective:To evaluate the efficacy and safety of Chinese medicinal formulae in the treatment of antimicrobial-resistant pneumonia. Method:Following article retrieval from eight databases and data extraction by two reviewers， the methodological quality of the included trials was assessed and the outcome indicators were subjected to Meta-analysis using RevMan 5.3. Result:A total of 24 randomized controlled trials （RCTs） were included， involving 1 818 cases. Meta-analysis showed that Chinese medicinal formulae combined with western routine intervention was superior to the western routine intervention in improving the overall response rate （ORR） ［relative risk （RR）=1.27， 95% confidence interval （CI） （1.21， 1.34）， P<0.000 01］， the bacterial clearance rate ［RR=1.49，95% CI （1.33， 1.66）， P<0.000 01］， and the clinical pulmonary infection score （CPIS） ［mean difference （MD）=-1.64， 95% CI （-1.87， -1.41）， P<0.000 01］. There was no significant difference in the incidence of adverse reactions ［RR=0.72， 95% CI （0.48， 1.07）， P=0.1］. The comparison with the western routine intervention also revealed that Chinese medicinal formulae better improved the ORR and CPIS. Conclusion:According to the current research results， the Chinese medicinal formulae alone or combined with western routine intervention yielded more favorable clinical outcomes than western routine intervention in the treatment of antimicrobial-resistant pneumonia， without increasing the incidence of adverse events. Due to limited quality and quantity of the included RCTs， more high-quality trials are required to verify the above conclusions.

The discovery of penicillin has effectively controlled the infection caused by Gram-positive bacteria. Afterwards, the research and development of antibacterial drugs has entered the golden age, and made a great contribution to human health. However, in recent years, with the increasing use of antibiotics around the world, pathogenic bacteria drive gene mutation to obtain drug resistance to ensure its survival advantage, and promote the transfer of drug-resistant genes, resulting in a sharp increase of drug-resistant bacteria. In addition, the current development speed of new antibiotics is far slower than the growth and spread speed of drug-resistant bacteria, which makes the drug-resistant crisis more serious and becomes one of the biggest threats to the global community. Compared with the same type of bacterial infection, drug-resistant bacterial infection has the characteristics of complexity and refractoriness, which causes worse clinical outcome and higher risk of death in patients, and brings severe challenges to clinical work. If the trend of bacterial drug resistance is not controlled, the crisis of no drug available will come. Therefore, it is urgent to explore effective alternative means to fight against bacterial drug resistance and reduce the harm of drug-resistant bacterial infection. Traditional Chinese medicine（TCM） has unique advantages in the treatment of infectious diseases. Compared with modern antibacterial drugs, it has the characteristics of wide sources, rich active ingredients, and is not easy to produce drug resistance. It may be an important source for screening and developing new anti-infective drugs. Therefore, it is promising to develop and utilize TCM to solve the problem of drug-resistant bacteria infection. This paper will review relevant studies in recent years in terms of interfering with the biochemical metabolism of drug-resistant bacteria to directly inhibit or kill drug-resistant bacteria, improving bacterial drug resistance to indirectly inhibit bacteria and kill bacteria, and maintaining the balance of the body and regulating the treatment of drug-resistant bacteria infection as a whole, so as to provide references for guiding clinical medication and research and development of new traditional Chinese medicines.

OBJECTIVE: To explore the mechanisms of angiogenesis in chronic myeloid leukemia (CML) through detecting the levels of angiogenesis-related factors secreted from K562 cells after overexpression and interference of HIF-1α gene in K562 cells. METHODS: The K562 cells were transfected by lentiviruses carried and interfered HIF-1α gene, then the transtected K562 cells with carried and interfered with HIF-1α gene were enrolled in overexpression and interference groups respectively, at the same time the K562 cells transfected by the empty virus were enrolled in control group. The cells were harvested after culture for 72 hours under normoxid condition. The transfection efficient in 3 groups was detected by fluorescence microscopy; the mRNA expression of HIF-1α gene and angiogenesis-related factors was detected by RT-PCR; the concentration of angiogenesis-related factors in the caltured supernatant was detected by ELISA. RESULTS: The optimal MOI of K562 cells transfected with lentivirus was 10 and the transfection efficiency was about 50%. The positive rate of transfection after screening by puromycin was more than 90%. The mRNA expression of ANG-I, ANG-II, TGF-α and VEGF in the interference group was lower than that in the over-expression group, and the TGF-β1 mRNA expression in the interference group was higher than in the over-expression group. The mRNA expression of ANG-I and VEGF in the interference group was lower than that in the control group. TGF-αdid not could be detected, and the culture supernatant concentration of ANG-I and TNF-α in the interference group was lower than in the over-expression group, while the VEGF concentration in the interference group was higher than that in the over-expression group. All of the above-mentioned differences were statistically significant (P＜0.05). CONCLUSION The positive K562 cells transfected with leutivirus have been harvested by screening with puromycin. The HIF-1α mRNA positively regulates the mRNA expression of ANG-1, ANG-2, TGF-α, VEGF in K562 cells, promotes the antocrine ability of ANG-1 and TNF-α, moreover not stimulates the autocrine of TGF-α, the up-regulation of HIF-1α expression can inhibit the expression TGF-β1 in K562 cells and the autocrine of TGF-β1.
Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; K562 Cells ; RNA, Messenger ; Vascular Endothelial Growth Factor A

OBJECTIVE: To investigate the clinical significance of bone marrow microvessel density(MVD) and angiogenesis related factors in multipic myeloma(MM). METHODS: Twenty cases of MM and 20 cases of simple fracture were selected and enrolled in MM group and control group respectively. The clinical data and results of laboratorial tests were collected; the bone marrow MVD of patients was detected by using the modified plastic-embedded pathologic sections of bone marrow tissue and histochemistry staining, the expression levels of amgiogenesis-related factors including VEGF, TNF-α, HGF, TGF-α, TGF-β1, bFGF, Ang-Ⅰ, Ang-Ⅱ in bone marrow supernatant were detected by ELISA; the mRNA expression levels of above-mentioned cytokines in bone marrow mononuclear cells were detected by real time-PCR; the pearson correlation analysis was used to analyze the correlation of MVD with VEGF, HGF and bFGF levels. RESULTS: The MVD in MM group was significantly higher than that in control group (P＜0.001); the mRNA expression of VEGF, TGF-α, TGF-β1 and HGF in bone marrow mononuclear cells of MM group was higher than that of control group(P＜0.001); the levels of VEGF, HGF, bFGF and THF-α in bone marrow supernatant of MM group were higher than those in control group(P＜0.05), moreover, the MVD positively correlated with levels of VEGF, HGF and bFGF in bone marrow(r=0.488, 0.472 and 0.457). CONCLUSION The MVD and levels vessel-related factors in bone marrow supernatant of MM patients increase, among which the levels of VEGF and HGF in bone marrow supernatant are consistant with those mRNA expression level in bone marrow mononuclear cells, moreover, the MVD possitively cerrelates with levels of VEGF, HGF and bFGF in bone marrow supernatant, suggesting that the changes of bone marrow microenvironment vassel-related factors play an important role in angiogenesis and pathogenesis of multiple myeloma.
Bone Marrow ; Bone Marrow Cells ; Humans ; Microvessels ; Multiple Myeloma ; Neovascularization, Pathologic ; Tumor Microenvironment

Diabetes mellitus complicated with cerebral infarction is the commonest and most serious vascular complication of diabetes mellitus. With a high disability and mortality rate, it seriously threatens human health. Because the pathogenesis is still unclear, more and more scholars have focused on the research of diabetic cerebral infarction at home and abroad. Traditional Chinese medicine(TCM) compounds have a remarkable curative effect in the treatment of diabetic cerebral infarction. Its mechanisms of action mainly include anti-hypertension, reduction of blood sugar and lipid, promotion of vascular regeneration and vascular endothelial function, anticoagulation, anti-thrombosis, improvement of nerve function defect, reduction of infarct volume, improvement of hemorheological, inhibition of inflammation and platelet aggregation, and promotion of collateral circulation. Through literature search, this paper summarizes the research progress of the mechanisms of TCM compounds in treating diabetic cerebral infarction in recent five years at home and abroad, in order to provide reference for clinical treatment.