Exploring an Integrative Therapy for Treating COVID-19: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVES@#To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients.@*METHODS@#A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed.@*RESULTS@#An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048).@*CONCLUSIONS@#Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).

Exploring an Integrative Therapy for Treating COVID-19: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVES@#To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients.@*METHODS@#A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed.@*RESULTS@#An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048).@*CONCLUSIONS@#Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).

Relationship Between Traditional Chinese Medicine(TCM)Constitution and TCM Syndrome in the Diagnosis and Treatment of Chronic Diseases / 中国医学科学杂志(英文版)

Chronic diseases are global threats to human health. By applying the traditional Chinese medicine (TCM) theory of body constitution to the treatment of chronic diseases, and comprehensively identifying and differentiating the syndrome, disease, and constitution, TCM can be fully used in the diagnosis and treatment of chronic diseases. In this manner, population-based and evidence-based modern medicine can organically align with the individual-focused and speculation-based TCM, with subsequent benefits for the control of chronic diseases, reducing their burden on human health.

Analysis of Clinical Characteristics in 595 Patients with Herb-induced Liver Injury / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe clinical characteristics of herb-induced liver injury (HILI).</p><p><b>METHODS</b>General conditions, medical history, clinical manifestations, biochemical indices, prognosis, and Roussed Uclaf Causality Assessment Method (RUCAM) scores were retrospectively analyzed in 595 inpatients at 302 Military Hospital between January 2009 and January 2014.</p><p><b>RESULTS</b>There were 423 cases (accounting for 71.1%) were females with multiple onset age ranging 41 to 50 years old. The median time from starting Chinese herbs to the occurrence of liver injury (LI) was 30 days (15-75 days), and 511 cases (85.9%) were classified as hepatocellular injury. Chinese herbs inducing HILI were mainly used for skin disease (102 cases, 17.1%), osteoarticular disease (57 cases, 9.6%), and gastrointestinal disease (49 cases, 8.2%), covering 207 kinds of Chinese patent medicines. Polygonum multiflorum, Psoralea corylifolia, and Corydalis ambigua were often seen in Chinese prescriptions. In RUCAM scoring, 451 HILI patients (accounting for 74.1%) were very possibly associated with Chinese herbs. Liver failure occurred in 47 HILI patients (accounting for 7.9%), cirrhosis in 45 patients (accounting for 7.6%), chronic HILI in 80 patients (accounting for 13.4%), 27 (4.5%) died, and only 2 (0.3%) underwent liver transplantation.</p><p><b>CONCLUSIONS</b>Chinese herbs could cause LI or even death. Attention should be paid to herbal hepatotoxicity and improving monitoring system of HILI.</p>

Clinical Analysis of Drug-induced Liver Injury Caused by Polygonum multiflorum and its Preparations / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To analyze hepatotoxicity of Polygonum multiflorum and clinical character- istics of drug-induced liver injury (DILI) caused by Polygonum multiflorum and its preparations.</p><p><b>METHODS</b>A retrospective study was performed in 158 patients treated at 302 Military Hospital between January 2009 and January 2014. All of them had used Polygonum multiflorum and its preparations before the onset of DILI, and their clinical characteristics and prognoses were analyzed.</p><p><b>RESULTS</b>Of the 158 DILI patients who used Polygonum multiflorum or its preparations, 92 (58.2%) combined with Western medicine or Chinese herbal preparations without Polygonum multiflorum; 66 patients (41.8%) used Polygonum mult florum and its preparations alone. In 66 DILI patients induced by Polygonum multiflorum or its preparations alone, 51 cases (77.3%) were induced by Polygonum multiflorum compounds and 22.7% by single Po- lygonum multiflorum; 4 cases (6.1%) were caused by crude Polygonum multiflorum and 62 (93.9%) by processed Polygonum multiflorum and its preparations. Clinical injury patterns were hepatocellular 92.4% (61 cases), cholestatic 1.5% (1 case), and mixed 6.1% (4 cases). Pathological examination was per- formed by liver biopsy in 32 cases (48.15%), manifested as hepatocellular degeneration and necrosis, fibroplasia, Kupffer cells with pigment granule, and a large number of eosinophil infiltration, were ob- served. Four patients were developed into liver failure, 4 into cirrhosis, and 1 died.</p><p><b>CONCLUSION</b>Polygo- num multiflorum and its preparations could induce DILI, but clinical diagnosis of Polygonum multiflorum induced hepatotoxicity should be cautious.</p>

Causes, Features, and Outcomes of Drug-Induced Liver Injury in 69 Children from China

BACKGROUND/AIMS: Drug-induced liver injury (DILI) is a frequent cause of pediatric liver disease; however, the data on DILI are remarkably limited. METHODS: All 69 children hospitalized with DILI between January 2009 and December 2011 were retrospectively studied. RESULTS: A total of 37.7% of the children had medical histories of respiratory infection. The clinical injury patterns were as follows: hepatocellular 89.9%, cholestatic 2.9%, and mixed 7.2%. Liver biopsies from 55 children most frequently demonstrated chronic (47.3%) and acute (27.3%) hepatitis. Hypersensitivity features, namely, fever (31.9%), rash (21.7%), and eosinophilia (1.4%), were found. Twenty-four children (34.8%) developed chronic DILI. Antibiotics (26.1%) were the most common Western medicines (WMs) causing DILI, and the major implicated herbs were Ephedra sinica and Polygonum multiflorum. Compared with WM, the children whose injuries were caused by Chinese herbal medicine (CHM) showed a higher level of total bilirubin (1.4 mg/dL vs 16.6 mg/dL, p=0.004) and a longer prothrombin time (11.8 seconds vs 17.3 seconds, p=0.012), but they exhibited less chronic DILI (2/15 vs 18/39, p=0.031). CONCLUSIONS: Most cases of DILI in children are caused by antibiotics or CHM used to treat respiratory infection and present with hepatocellular injury. Compared with WM, CHM is more likely to cause severe liver injury, but liver injury caused by CHM is curable.

In vitro and in vivo inhibitory effect of the combination of Wenxia Changfu formula see text with cisplatin in non-small cell lung cancer / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effect of the combination of Wenxia Changfu Formula ([see text], WCF) with cisplatin (CDDP) on inhibiting non-small cell lung cancer (NSCLC) in vitro and In Vivo and explore its mechanism from its effect on cell cycle.</p><p><b>METHODS</b>In vitro, WCF-containing serum was prepared and the rhubarb b1, emodin, and aconitine were detected qualitatively by high-performance liquid chromatogram (HPLC). A549 cell lines were treated with blank control (dimethyl sulfoxide), normal serum, normal serum with CDDP (1.25, 2.5, and 5.0 μg/mL, respectively), WCF-containing serum plus different doses of CDDP (1.25, 2.5, and 5.0 μg/mL, respectively). The inhibitory effect was detected by 3-(4,5)-dimethylthiazo(-zy1)-3,5-diphenylterazolium bromide (MTT). The cell cycle was detected by flow cytometry. The protein and mRNA expressions of cyclin D1, proliferating cell nuclear antigen (PCNA), retinoblastoma (Rb), and p16 were observed with immunofluorescence and RT-PCR, respectively. In Vivo, nude mice xenograft model was established and grouped into the control, CDDP, WCF, and combination groups. The combination's inhibition of tumor growth and influence on the weight, spleen, and thymus gland were observed.</p><p><b>RESULTS</b>The inhibitory rate of the combination against A549 cell lines excelled the CDDP alone significantly (P <0.05); the combination showed a synergism inhibitory effect (Q=1.19). Compared with the monotherapy, the combination increased the cell percentage in G(0)/G(1) phase and decreased the cell percentage in S phase significantly (P <0.05); the protein and mRNA expressions of cyclin D1, PCNA, and Rb were significantly reduced; the protein and mRNA expressions of p16 were significantly enhanced. Compared with the monotherapy, the combination inhibited the tumor growth significantly In Vivo and reduced the weight of tumor (P <0.05); compared with the CDDP group, the spleen and thymus gland index of the combination group were enhanced significantly (P <0.05).</p><p><b>CONCLUSIONS</b>The combination of WCF with CDDP significantly inhibited the A549 cell lines proliferation in vitro and the growth of the tumor In Vivo; it inhibited effectively the atrophy of the immune organ caused by chemotherapy. The combination inhibited overproliferation of A549 cell lines by arresting the G(0) /G(1) phase of cell cycle and affecting the protein and mRNA expressions of cell cycle-related proteins, cyclin D1, etc.</p>