Since the outbreak of coronavirus disease-19 (COVID-19) in Wuhan in December 2019, it has rapidly spread to the whole country and the world, causing serious harm to the health of people and a huge social burden. However, currently, there are no clinically available drugs, except for vaccines against COVID-19 that are being evaluated. Traditional Chinese medicine (TCM) is capable of performing syndrome differentiation and treatment according to the clinical manifestations of patients, and has a better ability of epidemic prevention and control. Therefore, we comprehensively analyzed the etiology and pathogenesis of COVID-19 based on the theory of TCM, and discussed its syndrome differentiation, treatment, and prevention measures to provide strategies and reference for the prevention and treatment of COVID-19 with TCM.

Objective
This meta-analysis was performed to assess the effects of L-arginine supplementation on indices of glycemic control, including fasting blood glucose (FBG), hemoglobin A1c (HbA1c), serum insulin and homeostatic model assessment of insulin resistance (HOMA-IR) levels in randomized controlled trials (RCTs).

Search strategy
This study conducted a systematic review of RCTs published in PubMed, Scopus, Web of Science, Cochrane Library and Embase, up to 5 May, 2018.

Inclusion criteria
Studies were included in this meta-analysis if they were RCTs with parallel design and reported sufficient data on participants before and after intervention, and outcomes of glycemic profile parameters in both the arginine supplementation and control groups.

Data extraction and analysis
The screening of titles and abstracts was performed independently by two reviewers. Selected articles were considered if they met the study’s inclusion criteria. The quality of included studies was assessed by using the Cochrane Collaboration modified tool. From 710 articles retrieved in the initial search, only 10 trials were suitable for pooling the effects of arginine supplementation on serum glucose, insulin, HOMA-IR and HbA1c levels, with effect sizes of nine, eight, five and five, respectively.

Conclusion
Although the results of this study confirmed that supplementation with L-arginine could have significant effects on some glycemic profile indices of participants in clinical trials, the clinical importance of this reduction may not be meaningful.

Results
Pooled random-effect analysis revealed that L-arginine supplementation could significantly decrease FBG level (weighted mean difference [WMD]: 3.35 mg/dL; 95% confidence interval [CI] = [–06.55, –00.16]; P = 0.04) and serum insulin level (WMD: –2.19 μIU/mL; 95% CI = [–3.70, –0.67]; P = 0.005). However, the effects of L-arginine supplementation on HOMA-IR and HbA1c were not significant. Results of subgroup analysis showed that supplementation with L-arginine could significantly decrease serum insulin levels when the dosage of L-arginine is > 6.5 g/d (WMD: –3.49 μIU/mL; 95% CI= [–5.59, –1.38]; P = 0.001), when the duration of supplementation is ≤ 12.8 weeks (WMD: –3.76; 95% CI = [–6.50, –0.98]; P = 0.008), when the participants are not diabetic patients (WMD: –2.54 μIU/mL; 95% CI= [–4.50, –0.50]; P= 0.01) and when the baseline serum level of insulin was > 20 μIU/mL (WMD: –3.98; 95% CI = [–6.31, –1.65]; P = 0.001).

Objective
The objective of this study was to systematically investigate the effects of TCEs on blood glucose control in patients with prediabetes.

Search strategy:
Comprehensive retrieval of randomized controlled trials (RCTs) was carried out using PubMed, Cochrane Library, EMbase, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Wanfang Data Knowledge Service Platform, China Biology Medicine disc, Google Scholar and Baidu academic databases. The retrieval window ranged from the establishment of the database to December 2018, and references related to the included trials were searched without language restrictions.

Inclusion criteria:
The study included RCTs with a clinical diagnosis of prediabetes that was also treated with TCEs.

Data extraction and analysis:
Literature screening, data extraction and literature quality assessment were performed independently by two researchers. In the case of disagreement, a third party was invited to negotiate and make a decision. Standardized mean difference (SMD) was used to estimate the therapeutic effect. Meta-analysis was performed using Review Manager 5.3.5 and Stata 15.0. Heterogeneity was assessed using Q test and I2, and the source of heterogeneity was determined using Galbraith diagram and sensitivity analysis. A Q test resulting in P < 0.1 and I2 > 50% indicated significant difference and random effect model analysis was performed. Otherwise, a fixed effect model was applied. Begg’s and Egger’s tests were used to assess publication bias.

Results
Nine RCTs involving 485 participants were included in this study. The results showed that TCEs could reduce fasting blood glucose (FBG), 2 h blood glucose (2hPBG) and HbA1c in patients with prediabetes. The treatment subgroup showed that an intervention of 6 months had better results, while the Gongfa subgroup showed that the TCE Baduanjin yielded better results. (1) FBG: SMD = –0.73, 95% confidence interval (CI) [–0.97, –0.50], P < 0.00001; Baduanjin: SMD = –0.83, 95% CI [–1.13, –0.53], P < 0.00001; 6 months treatment: SMD = –0.73, 95% CI [–1.20, –0.26], P = 0.002. (2) 2hPBG: SMD = –0.75, 95% CI [–0.94, –0.57], P < 0.00001; Baduanjin: SMD = –0.62, 95% CI [–0.91, –0.32], P < 0.00001; 6 months treatment: SMD = –0.91, 95% CI [–1.39, –0.44], P = 0.0002. (3) HbA1c: SMD = –0.56, 95% CI [–0.89, –0.23], P = 0.00008; Baduanjin: SMD = –0.46, 95% CI [–0.83, –0.08], P = 0.02; 6 months treatment: SMD = –0.77, 95% CI [–1.24, –0.29], P = 0.002.

Conclusion
TCEs had positive effects in improving blood glucose levels in patients with prediabetes. Hence, TCEs may be of potential therapeutic value for patients with prediabetes, as an adjuvant therapy along with other treatments. Although the evidence suggests that the intervention is effective for 6 months, the mechanism of TCEs on glycemic control, the minimum exercise dose and their safety remain to be further studied.

Objective
This review aims to evaluate the effectiveness and safety of cupping therapy in patients with CU.

Search strategy
The search strategy looked for the presence of related keywords, such as “chronic urticaria” and “cupping therapy,” in the title and abstract of research articles indexed in major databases. Randomized controlled trials (RCTs) were selected after querying nine electronic databases from their inception to May 2019 with the above search terms.

Inclusion criteria
RCTs were included if they recruited patients with CU who were intervened with dry or wet cupping. Publications could be written in Chinese or English.

Data extraction and analysis
Data were extracted, and the studies were assessed for the quality of their methodological design and risk of bias. Meta-analyses of the RCT data were conducted to assess the total effective rate of the treatment as the primary outcome. Skin disease quality of life index score, recurrence rate, and adverse events were assessed as secondary outcomes. Subgroup analyses were conducted based on different interventions.

Results
Thirteen comparisons from 12 RCTs involving 842 participants were included. There were no significant differences between wet cupping and medications in total effective rate (n = 372; risk ratio [RR] = 1.10, 95% confidence interval [CI] 0.97 to 1.25; P = 0.14) or recurrence rate (n = 240; RR = 0.56, 95% CI 0.23 to 1.36; P = 0.20). Cupping therapy, in combination with antihistamine treatment was more efficacious than antihistamines alone, with a greater total effective rate (n = 342; RR = 1.18, 95% CI 1.01 to 1.39; P = 0.03) and lower recurrence rate (n = 342; RR = 0.52, 95% CI 0.32 to 0.84; P = 0.007). Cupping therapy combined with acupuncture was more effective than acupuncture alone (n = 156; RR = 1.25, 95% CI 1.07 to 1.46; P = 0.006). No serious adverse events were reported.

Conclusion
Wet cupping may be as effective as treatment with antihistamines. When cupping therapy is used as an adjuvant therapy to antihistamines or acupuncture, it may enhance the efficacy. Results drawn from these studies should be interpreted with caution and applied with care to clinical practice, because of the poor quality among the studies that were reviewed.

Objective
To compare differences in self-reported musculoskeletal pain before and after receiving rapid acupuncture for pain at an outpatient emergency department.

Methods
Exactly 102 patients presenting to the emergency room of the Hospital Servidor Publico Estadual in Sao Paulo, Brazil, participated in this before-and-after study. All participants had musculoskeletal pain and were treated with the technique proposed by Marques Filho. This emergency acupuncture involved inserting a needle at a point defined by traditional Chinese medicine and applying intense stimulation for 10 s; no more than two points were used on any individual patient. Pain was measured using a numerical visual scale before and immediately after the procedure.

Results
Participants in this study were mostly women (78%), had a college degree (47%) and were below the age of 60 (56%). The most common region of pain was the lower back (31%), and the most common type of pain was acute and exacerbated chronic pain. The meridians most commonly involved were the eight extra meridians (40%), and the points most often used for treatment were Houxi (SI3), Shenmai (BL62) and Zulinqi (GB41). Almost all participants reported a decrease in pain intensity, independent of sex, education level, pain site and pain type (acute/chronic; P < 0.05). At the end of the session, only 4% of the participants reported a desire for allopathic medication.

Conclusion
This emergency acupuncture technique for analgesia appears to reduce musculoskeletal pain.

Objective

The drug sorafenib has been extensively used for the treatment of advanced hepatocellular carcinoma (HCC). Chinese herbal medicine has also been used to manage advanced HCC. The present work evaluates the effectiveness and safety of Jiedu (JD) granules, a compound of traditional Chinese herbal medicines, side-by-side with sorafenib for the treatment of advance HCC.

Methods

Patients with advanced HCC were enrolled in this study during December 2014 and March 2018. Study patients were elected to receive treatment with JD granules or sorafenib. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and safety. Propensity score matching (PSM) analysis was used to control for possible selection bias from the study group allocation process.

Results

Of the 325 patients included in this study, 161 received JD granules and 164 received sorafenib. No significant differences were found in OS or PFS among patients receiving JD granules compared to sorafenib (P > 0.05). Median OS of the two study groups was 6.83 months (95% confidence interval [CI]: 5.83–9.47) in the group receiving JD granules and 8 months (95% CI: 6.67–9.80) in the group receiving sorafenib, with half-, 1-, and 2- year survival rates of 53.6%, 31.2% and 13.2% vs 60.1%, 35.5% and 14.2%, respectively. Even after PSM, the median survival time did not differ between the JD granules group (9.03 months; 95% CI: 6.37–14.2) and the sorafenib group (7.93 months; 95% CI: 6.5–9.97), with comparable half-, 1- and 2-year survival rates. The most common adverse events (AEs) were diarrhea (13.7%) and fatigue (5.6%) in the JD granules group, and hand-foot skin reaction (46.3%) and diarrhea (36.6%) in the sorafenib group. The JD granules was more cost-effective than sorafenib treatment for advanced HCC.

Conclusion

Compared to sorafenib, JD granules provided a comparable treatment for HCC that was more cost-effective and caused fewer AEs for the treatment of Chinese patients with advanced HCC. 

Objective
To evaluate the cytotoxic, apoptotic, mutagenic and immunomodulatory activities of Kaempferia galanga Linn. (KG) extract and ethyl-p-methoxycinnamate (EPMC) in vitro.

Methods
The present study investigated the cytotoxic [using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide test], apoptotic (using a mitochondrial membrane potential assay), mutagenic (using a micronucleus test) and immunomodulatory (using flow cytometry) activities of the ethanolic extract of KG and its bioactive component, EPMC, against two cholangiocarcinoma (CCA) cell lines, CL-6 and HuCCT1, and one normal human cell line, OUMS-36T-1F.

Results
Both KG extract and EPMC exhibited moderate cytotoxic activity against both CCA cells. The cytotoxic activity was supported by their concentration-dependent induction of apoptosis. CL-6 was most sensitive (3–4 fold) and selective to 5-fluorouracil (5-FU), compared with KG extract and EPMC [median half inhibiting concentration (IC₅₀) and selectivity index (SI) were 23.01 μg/mL and 17.32; 78.41 μg/mL and 4.44; 100.76 μg/mL and 2.20, respectively for 5-FU vs. KG extract vs. EPMC]. HuCCT1 was relatively more sensitive and selective to 5-FU and EPMC than KG extract [median IC₅₀ and SI were 66.03 μg/mL and 6.04; 60.90 μg/mL and 3.65; 156.60 μg/mL and 2.23, respectively for 5-FU vs. EPMC vs. KG extract]. EPMC produced relatively potent cytotoxic activity against polymorphonuclear cells (IC₅₀ = 92.20 μg/mL). KG extract and EPMC exhibited concentration-dependent mutagenic activity, as well as inhibition of tumor necrosis factor-α and interleukin-6.

Conclusion
Considering cytotoxic, apoptotic, immunomodulatory and mutagenic activities, further development of KG as a drug candidate is likely to focus on the oral pharmaceutical formulation of a standardized KG extract rather than isolated compounds.

Objective
To investigate the effects of Aurantii Fructus Immaturus (Zhishi, ZS) and Atractylodis Macrocephalae Rhizoma (Baizhu, BZ)-containing serum on glutamate-induced autophagy in rat colonic interstitial cells of Cajal (ICCs) and to analyze the underlying mechanism.

Methods
Rat colonic ICCs cultured in vitro were identified by fluorescence and then stimulated with glutamic acid (5 mmol/L) for 24 h to establish a cell model of autophagy. The cells were then treated with different concentrations of ZSBZ-containing serum or rat serum. The viability of the ICCs was detected with cell counting kit-8 assays, and cell apoptosis rates were examined with flow cytometry. The ultrastructure and autophagosomes in the ICCs were observed using transmission electron microscopy. The effects of ZSBZ-containing serum on apoptosis-associated mediators were assessed by Western blotting and real-time quantitative polymerase chain reaction. In addition, microtubule-associated protein light chain 3 (LC3), p-phosphoinositide 3-kinase (p-PI3K), p-Akt and p-mammalian target of rapamycin (p-mTOR) expression was detected via Western blotting analysis.

Results
Compared to those in the model group, ICC viability and apoptosis rates were significantly increased by ZSBZ-containing serum (P < 0.05). In addition, the expression levels of Beclin-1, LC3, p-PI3K, p-Akt and p-mTOR were significantly lower (P < 0.05) and Bcl-2 expression was higher in the ZSBZ-containing serum treatment groups than in the model group (P < 0.05).

Conclusion
Our findings demonstrated that ZSBZ protects glutamic acid-stimulated ICCs, and this beneficial effect may be mediated by a reduction in autophagy via inhibition of the PI3K/Akt/mTOR pathway.

Objective
Our previous research showed that Naotaifang (a compound traditional Chinese herbal medicine) extract (NTE) has clinically beneficial effects on neurological improvement of patients with acute cerebral ischemia. In this study, we investigated whether NTE protected acute brain injury in rats and whether its effects on ferroptosis could be linked to the dysfunction of glutathione peroxidase 4 (GPX4) and iron metabolism.

Methods
We established an acute brain injury model of middle cerebral artery occlusion (MCAO) in rats, in which we could observe the accumulation of iron in neurons, as detected by Perl’s staining. Using assay kits, we measured expression levels of ferroptosis biomarkers, such as iron, glutathione (GSH), reactive oxygen species (ROS) and malonaldehyde (MDA); further the expression levels of transferrin receptor 1 (TFR1), divalent metal transporter 1 (DMT1), solute carrier family 7 member 11 (SLC7A11) and GPX4 were determined using immunohistochemical analysis, real-time quantitative polymerase chain reaction and Western blot assays.

Results
We found that treatment with NTE reduced the expression levels of TFR1 and DMT1, reduced ROS, MDA and iron accumulation and reduced neurobehavioral scores, relative to untreated MCAO rats. Treatment with NTE increased the expression levels of SLC7A11, GPX4 and GSH, and the number of Nissl bodies in the MCAO rats.

Conclusion
Taken together, our data suggest that acute cerebral ischemia induces neuronal ferroptosis and the effects of treating MCAO rats with NTE involved inhibition of ferroptosis through the TFR1/DMT1 and SCL7A11/GPX4 pathways.

Objective
Critical effective constituents were identified from Bufei Yishen formula (BYF), a traditional herbal compound and combined as effective-constituent compatibility (ECC) of BYF I, which may have potential bioactive equivalence to BYF.

Methods
The active constituents of BYF were identified using four cellular models and categorised into Groups 1 (Bufeiqi), 2 (Bushen), 3 (Huatan) and 4 (Huoxue) according to Chinese medicinal theory. An orthogonal design and a combination method were used to determine the optimal ratios of effective constituents in each group and the ratios of “Groups 1 to 4” according to their pharmacological activity. We also comprehensively assessed bioactive equivalence between the BYF and the ECC of BYF I in a rat model of chronic obstructive pulmonary disease (COPD).

Results
We identified 12 active constituents in BYF. The numbers of constituents in Groups 1 to 4 were 3, 2, 5 and 2, respectively. We identified the optimal ratios of effective constituents within each group. In Group 1, total ginsenosides:Astragalus polysaccharide:astragaloside IV ratio was 9:5:2. In Group 2, icariin:schisandrin B ratio was 100:12.5. In Group 3, nobiletin:hesperidin:peimine:peiminine:kaempferol ratio was 4:30:6.25:0:0. In Group 4, paeoniflorin:paeonol ratio was 4:1. An orthogonal design was then used to establish the optimal ratios of Group 1, Group 2, Group 3 and Group 4 in ECC of BYF I. The ratio for total ginsenosides:Astragalus polysaccharide:astragaloside IV:icariin:schisandrin B:nobiletin:hesperidin:peimine:paeoniflorin:paeonol was determined to be 22.5:12.5:5:100:12.5:4:30:6.25:25:6.25. A comprehensive evaluation confirmed that ECC of BYF I presented with bioactive equivalence to the original BYF.

Conclusion
Based on the ECC of traditional Chinese medicine formula method, the effective constituents of BYF were identified and combined in a fixed ratio as ECC of BYF I that was as effective as BYF itself in treating rats with COPD.