Human papillomavirus 16 E6/E7 contributes to immune escape and progression of cervical cancer by regulating miR-142-5p/PD-L1 axis.

Persistent infection of human papillomavirus (HPV) and immune escape are the main causes of cervical cancer. E6/E7 encoded by HPV16 may be closely related to carcinogenesis. HPV infection may upregulate PD-L1 expression, resulting in immune escape and cervical cancerigenesis. Evidence indicates that miRNAs may mediate the regulation of E6/E7 on PD-L1. Therefore, we aimed to screen the miRNA, and further verify its expression and functions. Bioinformatics approaches were used to screen the miRNAs that mediate the regulation of E6/E7 on PD-L1. The expression of the miRNA and PD-L1 in HPV+ and HPV- cervical cancer cells were compared, and the effect of E6E7 on them was evaluated. Then, the effect of the miRNA on PD-L1 was assessed by the Gain- and Loss-of-function test. Finally, in vivo experiments were conducted to verify the effects of the miRNA on tumor growth and survival of tumor-bearing mice. Six miRNAs were screened, of which miR-142-5p was identified. MiR-142-5p was downregulated and PD-L1 was upregulated in HPV- cells after transfection of E6, E7, or E6/E7. The rescue test showed that the upregulation of miR-142-5p attenuated the effect of E6/E7 on PD-L1. The reverse relationship between PD-L1 and miR-142-5p was confirmed. In vivo experiments suggest that miR-142-5p upregulation inhibits the growth of the transplanted tumors by targeting PD-L1. MiR-142-5p acts as a tumor suppressor in cervical cancer. HPV16 E6E7 may promote the immune escape of cervical cancer cells by regulating the miR-142-5p/PD-L1 axis. Using miR-142-5p in tumor immunotherapy as a new strategy is proposed.

Chinese Medicine Formula Huashibaidu Granule Early Treatment for Mild COVID-19 Patients: An Unblinded, Cluster-Randomized Clinical Trial.

Background: Previous research suggested that Chinese Medicine (CM) Formula Huashibaidu granule might shorten the disease course in coronavirus disease 2019 (COVID-19) patients. This research aimed to investigate the early treatment effect of Huashibaidu granule in well-managed patients with mild COVID-19. Methods: An unblinded cluster-randomized clinical trial was conducted at the Dongxihu FangCang hospital. Two cabins were randomly allocated to a CM or control group, with 204 mild COVID-19 participants in each cabin. All participants received conventional treatment over a 7 day period, while the ones in CM group were additionally given Huashibaidu granule 10 g twice daily. Participants were followed up to their clinical endpoint. The primary outcome was worsening symptoms before the clinical endpoint. The secondary outcomes were cure and discharge before the clinical endpoint and alleviation of composite symptoms after the 7 days of treatment. Results: All 408 participants were followed up to their clinical endpoint and included in statistical analysis. Baseline characteristics were comparable between the two groups (P > 0.05). The number of worsening patients in the CM group was 5 (2.5%), and that in the control group was 16 (7.8%) with a significant difference between groups (P = 0.014). Eight foreseeable mild adverse events occurred without statistical difference between groups (P = 0.151). Conclusion: Seven days of early treatment with Huashibaidu granule reduced the likelihood of worsening symptoms in patients with mild COVID-19. Our study supports Huashibaidu granule as an active option for early treatment of mild COVID-19 in similar well-managed medical environments. Clinical Trial Registration:www.chictr.org.cn/showproj.aspx?proj=49408, identifier: ChiCTR2000029763.

Combination of Hua Shi Bai Du granule (Q-14) and standard care in the treatment of patients with coronavirus disease 2019 (COVID-19): A single-center, open-label, randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of Hua Shi Bai Du Granule (Q-14) plus standard care compared with standard care alone in adults with coronavirus disease (COVID-19). STUDY DESIGN: A single-center, open-label, randomized controlled trial. SETTING: Wuhan Jinyintan Hospital, Wuhan, China, February 27 to March 27, 2020. PARTICIPANTS: A total of 204 patients with laboratory-confirmed COVID-19 were randomized into the treatment group and control group, consisting of 102 patients in each group. INTERVENTIONS: In the treatment group, Q-14 was administered at 10 g (granules) twice daily for 14 days, plus standard care. In the control group, patients were provided standard care alone for 14 days. MAIN OUTCOME MEASURE: The primary outcome was the conversion time for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral assay. Adverse events were analyzed in the safety population. RESULTS: Among the 204 patients, 195 were analyzed according to the intention-to-treat principle. A total of 149 patients (71 vs. 78 in the treatment and control groups, respectively) tested negative via the SARS-CoV-2 viral assay. There was no statistical significance in the conversion time between the treatment group and control group (Full analysis set: Median [interquartile range]: 10.00 [9.00-11.00] vs. 10.00 [9.00-11.00]; Mean rank: 67.92 vs. 81.44; P = 0.051). The recovery time for fever was shorter in the treatment group than in the control group. The disappearance rate of symptoms like cough, fatigue, and chest discomfort was significantly higher in the treatment group. In chest computed tomography (CT) examinations, the overall evaluation of chest CT examination after treatment compared with baseline showed that more patients improved in the treatment group. There were no significant differences in the other outcomes. CONCLUSION: The combination of Q-14 and standard care for COVID-19 was useful for the improvement of symptoms (such as fever, cough, fatigue, and chest discomfort), but did not result in a significantly higher probability of negative conversion in the SARS-CoV-2 viral assay. No serious adverse events were observed. TRIAL REGISTRATION: ChiCTR2000030288.

Efficacy and safety assessment of severe COVID-19 patients with Chinese medicine: A retrospective case series study at early stage of the COVID-19 epidemic in Wuhan, China.

ETHNOPHARMACOLOGICAL RELEVANCE: The coronavirus disease 2019 (COVID-19) has formed a global pandemic since late 2019. Benefitting from the application experience of Chinese Medicine (CM) for influenza and SARS, CM has been used to save patients at the early stage of COVID-19 outbreak in China. AIM OF THE STUDY: In order to evaluate the efficacy and safety of CM, and compare with Western Medicine (WM) for COVID-19, we conducted a retrospective case series study based on the patients in Wuhan Jinyintan Hospital, Wuhan, China. METHODS: The inclusion and exclusion criteria of data extraction were set for this retrospective study. All patients who were admitted by the Wuhan Jinyintan Hospital between January 17th and February 25th 2020 were considered. In addition, patients enrolled met the severe defined by the guidelines released by the National Health Commission of the People's Republic of China. In these cases included in the study, CM or WM treatment was selected according to the wishes of the patients at the beginning of hospitalization. The patients in CM group were treated with Huashi Baidu granule (137 g po, bid) combined with the injections of Xiyanping (100 mg iv, bid), Xuebijing (100 ml iv, bid) and Shenmai (60 ml iv, qd) according to the syndrome of epidemic toxin blocking the lung in the theory of Traditional Chinese Medicine. The WM group received antiviral therapy (including abidor capsule 0.2 g po, tid; Lopinavir-Ritonavir tablets, 500 mg po, bid), antibiotics (such as cefoperazone 2 g iv, bid; moxifloxacin hydrochloride tablets, 0.4 g po, qd) or corticosteroid therapy (such as methylprednisolone succinate sodium 40 mg iv, qd; prednisone, 30 mg po, qd). In addition, patients in both groups received routine supportive treatment, including oxygen inhalation, symptomatic therapy, and/or human intravenous immunoglobulin, and/or serum albumin, and treatment for underlying diseases. The clinical outcomes were evaluated based on changes related with clinical manifestations, computer tomography (CT) scan images, and laboratory examinations before and after the treatment. RESULTS: 55 severe COVID-19 patients, with 23 in CM group and 32 in WM group, were included for analyzed. There was no case of death, being transferred to ICU, or receiving invasive mechanical ventilation in two groups during hospitalization. The median time of SARS-CoV-2 RNA clearance in CM and WM group were 12 days and 15.5 days respectively, the ratio of nucleic acid negative conversion of CM group at different follow-up time points was significantly higher than that of WM group (HR: 2.281, P = 0.018). Further, the chest CT imaging showed more widely lung lesion opacity absorbed in the CM group. The high sensitivity C-reactive protein and serum ferritin decreased significantly in the CM group (P<0.05). There was no significant difference in adverse events in terms of liver function and renal function between the two groups. CONCLUSION: Based on this retrospective analysis from Wuhan Jinyintan Hospital, CM has better effects in SARS-CoV-2 RNA clearance, promoting lung lesion opacity absorbed and reducing inflammation in severe COVID-19 patients, which is effective and safe therapy for treating severe COVID-19 and reducing mortality.

Efficacy and safety of Chinese herbal medicine versus Lopinavir-Ritonavir in adult patients with coronavirus disease 2019: A non-randomized controlled trial.

BACKGROUND: Treatments for coronavirus disease 2019 (COVID-19) are limited by suboptimal efficacy. METHODS: From January 30, 2020 to March 23, 2020, we conducted a non-randomised controlled trial, in which all adult patients with laboratory-confirmed COVID-19 were assigned to three groups non-randomly and given supportive treatments: Group A, Lopinavir-Ritonavir; Group B, Huashi Baidu Formula (a Chinese medicineformula made by the China Academy of Chinese Medical Sciences to treat COVID-19, which is now in the clinical trial period) and Lopinavir-Ritonavir; and Group C, Huashi Baidu Formula. The use of antibiotics, antiviruses, and corticosteroids was permitted in Group A and B. Traditional Chinese medicine injections were permitted in Group C. The primary outcomes were clinical remission time (interval from admission to the first time the patient tested negatively for novel coronavirus or an obvious improvement was observed from chest CT) and clinical remission rate (number of patients whose clinical time was within 16 days/total number of patients). RESULTS: A total of 60 adult patients with COVID-19 were enrolled at sites in Wuhan, China, and the sample size of each group was 20. In Groups A, B and C, the clinical remission rates were 95.0%%(19/20), 100.0%%(20/20) and 100.0%%(20/20), respectively. Compared with Groups A and B, the clinical remission time of Group C was significantly shorter (5.9 days vs. 10.8 days, p < 0.05; 5.9 days vs. 9.7 days, p < 0.05). There was no significant difference among Groups A, B, and C in terms of the time taken to be released from quarantine. The clinical biochemical indicators and safety indexes showed no significant differences among the three groups. CONCLUSIONS: Our findings suggest that Lopinavir-Ritonavir has some efficacy in the treatment of COVID-19, and the Huashi Baidu Formula might enhance this effect to an extent. In addition, superiority was displayed in the treatment of COVID-19 through a combination of the Huashi Baidu Formula and traditional Chinese medicine injection. In future, well-designed prospective double-blinded randomised control trials are required to confirm our findings.

Effectiveness and safety of auricular acupoint bloodletting in treatment of insomnia: an assessor-blinded pilot randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness and safety of auricular acupoint bloodletting in treatment of insomnia METHODS: Participants (n = 60) with insomnia were randomized into two groups to receive treatment of auricular acupoint bloodletting: low frequency group, 1 times/week for five weeks (n = 30); high frequency group, 2times/week for two weeks (n = 30). The following outcomes were measured blindly at baseline, after first treatment, 4 weeks, and 8 weeks: Pittsburgh sleep quality index scale (PSQI). RESULTS: The groups were balanced at baseline for insomnia and demographic characteristics. There were no significant differences between the groups in terms of any of the outcomes, at the first follow-up time point. However, the therapeutic effect of LFG (once per week) is obviously lower than that of HFG (twice per week). In addition, there was no significant difference in the side effects between the two groups. CONCLUSION: The treatment of insomnia with different frequencies of auricular acupoint bloodletting is effective and has less side effects. More reasonable treatment frequencies are worth further study.

Influence of clinical pathways used the hospitals of Traditional Chinese Medicine on patients hospitalized with stroke: a systematic review and Meta-analysis.

OBJECTIVE: To evaluate the influence of clinical pathways in the hospitals using the Traditional Chinese Medicine in treatment of stroke in terms of postoperative complications, length of stay (LOS), costs incurred during hospitalization, compared with standard medical care. METHODS: Medline, Embase, China National Knowledge Infrastructure (CNKI) platforms, Wanfang databases and the Cochrane Central Register of Controlled Trials were searched. The search was performed up to August 2014. Each study was assessed independently by two reviewers. The assessment of methodological quality of the included studies was based on the Methodological index for non-randomized studies standard. Meta-analyses were performed using RevMan software, version 5.0. RESULTS: Six studies met the study inclusion criteria and were included in the Meta-analysis for a total sample of 710 patients. The aggregate overall results showed that shorter length of stay in the clinical pathway group was observed during hospital stay was associated with the use of the clinical pathways. No significant differences were found in other effects. CONCLUSION: Regardless the possible limitations, our findings show that clinical pathways can significantly reduce LOS. Although there is no clear evidence that clinical pathways can reduce hospital costs, but the cost of hospitalization path group for each included study were lower than the control group.