This document is the revised edition of the previously issued Shanghai Expert Consensus on Clinical Protocol for Traditional Chinese Medicine Treatment of COVID-19 among the Elderly Population. Based on the clinical experience and the Protocol for Diagnosis and Treatment of COVID-19 (Trial 9th Edition), this revised edition provides treatment approaches and recommendations to proactively cope with Omicron variant and increase the therapeutic efficacy for coronavirus disease 2019 among the elderly population in Shanghai, China.

Background

Functional constipation (FC) is one of the most prevalent functional gastrointestinal disorders. Dissatisfaction with medications prescribed to treat FC may lead patients to seek alternative treatments. Numerous systematic reviews (SRs) examining the use of acupuncture to treat FC have reported inconsistent results, and the quality of these studies has not been fully evaluated.

Objective

In this overview, we evaluated and summarized clinical evidence on the effectiveness and safety of acupuncture for treating FC and evaluated the quality and bias of the SRs we reviewed.

Search strategy

The search strategy was structured by medical subject headings and search terms such as “acupuncture therapy” and “functional constipation.” Electronic searches were conducted in eight databases from their inception to September 2020.

Inclusion criteria

SRs that investigated the effectiveness and safety of acupuncture for managing FC were included.

Data extraction and analysis

Two authors independently extracted information and appraised the methodology, reporting accuracy, quality of evidence, and risk of bias using the following critical appraisal tools: (1) A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2); (2) Risk of Bias in Systematic Reviews (ROBIS); (3) Preferred Reporting Items for Systematic Reviews and Meta-analyses for Acupuncture (PRISMA-A); and (4) the Grading of Recommendations, Assessment, Development and Evaluations (GRADE). A κ index was used to score the level of agreement between the 2 reviewers.

Results

Thirteen SRs that examined the clinical utility of acupuncture for treating FC were identified. Using the AMSTAR 2 tool, we rated 92.3% (12/13) of the SRs as “critically low” confidence and one study as “low” confidence. Using the ROBIS criteria, 38.5% (5/13) of the SRs were considered to have “low risk” of bias. Based on PRISMA-A, 76.9% (10/13) of the SRs had over 70% compliance with reporting standards. The inter-rater agreement was good for AMSTAR 2, ROBIS, and PRISMA-A. Using the GRADE tool, we classified 22.5% (9/40) of the measured outcomes as “moderate” quality, 57.5% (23/40) as “low” quality, and 20.0% (8/40) as “very low” quality. The inter-rater agreement was moderate when using GRADE. Descriptive analyses indicated that acupuncture was more efficacious than sham acupuncture for improving weekly complete spontaneous bowel movements (CSBMs) and for raising the Bristol Stool Form Scale (BSFS) score. Acupuncture appeared to be superior to anti-constipation drugs for improving weekly spontaneous bowel movements, the total effective rate, and the Patient Assessment of Constipation Quality of Life score. Although ten SRs mentioned the occurrence of adverse events, serious adverse events were not associated with acupuncture treatment.

Conclusion

Acupuncture may be more efficacious than sham acupuncture for improving CSBMs and BSFS scores and may be superior to anti-constipation drugs for improving bowel movement frequency, as well as quality of life. Limitations to current studies and inconsistent evidence suggest a need for more rigorous and methodologically sound SRs to draw definitive conclusions.

Systematic review registration

PROSPERO CRD42020189173.

Objective

We employed a multidisciplinary approach incorporating theoretical ideas, clinical experience, psychology, physiology, traditional Chinese medicine (CM), modern practice of CM, and oncology to explore the effect of patients’ repression of negative emotions and traumatic events on breast cancer (BC) pathogenesis.

Methods

BC female patients, older than 18 years of age, with available pathology reports who were treated at Rabin Medical Center were recruited. All participants completed questionnaires regarding medical history, behavioral tendencies, negative emotions, trauma, symptoms, and pathology (from a CM perspective). Data on tumor characteristics were collected from the pathology reports. The associations were examined using hierarchical binary logistic regressions. 

Results

A total of 155 BC patients were enrolled. The median age was 52 years, with a range of 26–79; 95% were mothers; 28% had estrogen receptor (ER)-negative BC, 52% had progesterone receptor (PR)-negative BC, 48% had human epidermal growth factor receptor 2-negative BC, and antigen Ki-67 ≥ 20% was reported for 52% of tumors. Statistically significant associations were found between the emotional markers (sense of motherhood failure, and lack of self-fulfillment), avoidance behavior, and physical symptoms that are related to emotional repression based on CM. Significant associations were also found between variables associated with physical symptoms of emotional repression, which involves the production and accumulation of non-substantial phlegm (i.e., “high-lipid Qi-like microscopic phlegm”), avoidance behavior which unconsciously uses “high-lipid Qi-like microscopic phlegm” in order to achieve emotional repression, and tumor parameters including tumor grade, PR status, and Ki-67. Patients with higher levels of “high-lipid Qi-like microscopic phlegm” were more likely to have tumors with worse prognosis (PR-negative, higher grade, and higher Ki-67). 

Conclusion

We demonstrated a relationship between emotional parameters, behavioral tendencies, CM parameters, and oncologic parameters in BC. Additional research is warranted to explore these associations and their relevance to clinical practice. 

Artemisia annua and its phytocompounds have a rich history in the research and treatment of malaria, rheumatoid arthritis, systemic lupus erythematosus, and other diseases. Currently, the World Health Organization recommends artemisinin-based combination therapy as the first-line treatment for multi-drug-resistant malaria. Due to the various research articles on the use of antimalarial drugs to treat coronaviruses, a question is raised: do A. annua and its compounds provide anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) properties. PubMed/MEDLINE, Scopus, and Google Scholar were searched for peer-reviewed articles that investigated the antiviral effects and mechanisms of A. annua and its phytochemicals against SARS-CoVs. Particularly, articles that studied the herb’s role in inhibiting the coronavirus-host proteins were favored. Nineteen studies were retrieved. From these, fourteen in silico molecular docking studies demonstrated potential inhibitory properties of artemisinins against coronavirus-host proteins, including 3CLPRO, S protein, N protein, E protein, cathepsin-L, helicase protein, nsp3, nsp10, nsp14, nsp15, and GRP78 receptor. Collectively, A. annua constituents may impede the SARS-CoV-2 attachment, membrane fusion, and internalization into the host cells, and hinder the viral replication and transcription process. This is the first comprehensive overview of the application of compounds from A. annua against SARS-CoV-2/coronavirus disease 2019 (COVID-19) describing all target proteins. A. annua’s biological properties, the signaling pathways implicated in the COVID-19, and the advantages and disadvantages for repurposing of A. annuacompounds are discussed. The combination of A. annua’s biological properties, action on different signaling pathways and target proteins, and a multi-drug combined-therapy approach may synergistically inhibit SARS-CoV-2 and assist in the COVID-19 treatment. Also, A. annua may modulate the host immune response to better fight the infection. 

Background
Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.

Objective
This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium.

Design, setting, participants and intervention
This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18–70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m², and 24-hour proteinuria level of 0.5–3.0 g, were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups: SYKFT, losartan potassium 50 mg or 100 mg, SYKFT plus losartan potassium 50 mg or 100 mg.

Main outcome measures
The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment.

Results
A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group.

Conclusion
SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.

Trial registration number
NCT02063100 on ClinicalTrials.gov.

Objective
Traditional Chinese medicine plays a significant role in the treatment of the pandemic of coronavirus disease 2019 (COVID-19). Tanreqing Capsule (TRQC) was used in the treatment of COVID-19 patients in the Shanghai Public Health Clinical Center. This study aimed to investigate the clinical efficacy of TRQC in the treatment of COVID-19.

Methods
A retrospective cohort study was conducted on 82 patients who had laboratory-confirmed mild and moderate COVID-19; patients were treated with TRQC in one designated hospital. The treatment and control groups consisted of 25 and 57 cases, respectively. The treatment group was given TRQC orally three times a day, three pills each time, in addition to conventional Western medicine treatments which were also administered to the control group. The clinical efficacy indicators, such as the negative conversion time of pharyngeal swab nucleic acid, the negative conversion time of fecal nucleic acid, the duration of negative conversion of pharyngeal-fecal nucleic acid, and the improvement in the level of immune indicators such as T-cell subsets (CD3, CD4 and CD45) were monitored.

Results
COVID-19 patients in the treatment group, compared to the control group, had a shorter negative conversion time of fecal nucleic acid (4 vs. 9 days, P = 0.047) and a shorter interval of negative conversion of pharyngeal-fecal nucleic acid (0 vs. 2 days, P = 0.042). The level of CD3⁺ T cells increased in the treatment group compared to the control group ([317.09 ± 274.39] vs. [175.02 ± 239.95] counts/μL, P = 0.030). No statistically significant differences were detected in the median improvement in levels of CD4⁺ T cells (173 vs. 107 counts/μL, P = 0.208) and CD45⁺ T cells (366 vs. 141 counts/μL, P = 0.117) between the treatment and control groups.

Conclusion
Significant reductions in the negative conversion time of fecal nucleic acid and the duration of negative conversion of pharyngeal-fecal nucleic acid were identified in the treatment group as compared to the control group, illustrating the potential therapeutic benefits of using TRQC as a complement to conventional medicine in patients with mild and moderate COVID-19. The underlying mechanism may be related to the improved levels of the immune indicator CD3⁺ T cells.

Background
There is currently no drug or therapy that cures COVID-19, a highly contagious and life-threatening disease.
Objective
This systematic review and meta-analysis summarized contemporary studies that report the use of Chinese herbal medicine (CHM) to treat COVID-19.
Search strategy: Six electronic databases (PubMed/MEDLINE, Cochrane Library, ScienceDirect, Google Scholar, Wanfang Data and China National Knowledge Infrastructure) were searched from their beginning to May 15, 2020 with the following search terms: traditional Chinese medicine, Chinese medicine, Chinese herbal medicine, COVID-19, new coronavirus pneumonia, SARS-CoV-2, and randomized controlled trial.
Inclusion criteria: Randomized controlled trials (RCTs) from peer-reviewed journals and non-reviewed publications were included. Further, included RCTs had a control group that was given standard care (SC; such as conventional Western medicine treatments or routine medical care), and a treatment group that was given SC plus CHM.
Data extraction and analysis: Two evaluators screened and collected literature independently; information on participants, study design, interventions, follow-up and adverse events were extracted, and risk of bias was assessed. The primary outcomes included scores that represented changes in symptoms and signs over the course of treatment. Secondary outcomes included the level of inflammatory markers, improvement of pneumonia confirmed by computed tomography (CT), and adverse events. Dichotomous data were expressed as risk ratio or hazard ratio with 95% confidence interval (CI); where time-to-event analysis was used, outcomes were expressed as odds ratio with 95% CI. Continuous data were expressed as difference in means (MD) with 95% CI, and standardized mean difference (SMD) was used when different outcome scales were pooled.
Results
Seven original studies, comprising a total of 732 adults, were included in this meta-analysis. Compared to SC alone, CHM plus SC had a superior effect on the change of symptom and sign score (–1.30 by SMD, 95% CI [–2.43, –0.16]; 3 studies; n = 261, P = 0.03), on inflammatory marker C-reactive protein (CRP, mg/L; –11.82 by MD, 95% CI [–17.95, –5.69]; 5 studies; n = 325, P = 0.0002), on number of patients with improved lung CT scans (1.34 by risk ratio, 95% CI [1.19, 1.51]; 4 studies; n = 489, P < 0.00001). No significant adverse events were recorded in the included RCTs.

Conclusion
Current evidence shows that CHM, as an adjunct treatment with standard care, helps to improve treatment outcomes in COVID-19 cases.

Objective 

The Lung-toxin Dispelling Formula No.1 (referred to as Respiratory Detox Shot, RDS) was established based on the theory of traditional Chinese medicine (TCM) medicinal properties and the classical prescription of TCM. It has demonstrated therapeutic benefits in both disease control and prevention in the effort to contain corona virus disease 2019 (COVID-19). However, the material basis and action mechanism of RDS are still unclear. The goal of the study is to clarify the material foundation and action mechanism of RDS.

Methods 

To achieve in-depth analyses of RDS from a holistic perspective, an integrative analytical platform was constructed, including target prediction, protein-protein interaction (PPI) network, cluster analysis, and the hub genes involved in the disease pathways were identified, and their corresponding compounds were further applied to molecular docking for in vitro biological validation. The presence of the validated compounds was also measured to demonstrate the material basis of RDS. In our network pharmacology study, a total of 26 bioinformatic software and databases were accessed, and 6 networks covering the entire Zang-fu viscera were constructed to achieve comprehensive analysis and visualization of the intricate connections among the compounds-targets-disease pathway-meridians of RDS.

Results 

For all 1071 compounds of 9 ingredients of RDS from established TCM databases, 157 compounds passed drug-likeness screening and led to 339 predicted targets in the compound-target network. 42 hub genes with core regulatory effects were extracted from the PPI network, and 134 compounds and 29 crucial disease pathways were implicated in the target-compound-disease network. Twelve disease pathways attributed to Lung-Large intestine meridian, with 6 and 5 to Kidney-Urinary bladder and Stomach-Spleen meridians, respectively. 118 candidate compounds showed a high binding affinity with SARS-CoV-2 3-chymotrypsin-like protease (3CL^pro) by molecular docking using computational pattern recognition. The in vitro activity of 22 compounds was validated by the 3CL^pro inhibition assay. Finally, using the technique of liquid chromatography mass spectrometry in data-independent analysis mode, 7 out of 22 compounds were confirmed and validated in RDS aqueous decoction with reference standards in both non-targeted and targeted approaches.

Conclusion 

Our results unveiled that RDS acts primarily in the Lung-Large intestine, Kidney-Urinary bladder, and Stomach-Spleen meridians, with other Zang-fu viscera strategically covered by all 9 ingredients. Integrated with the context of TCM meridian theory, multiple components and targets of RDS demonstrate the action dual effects of health-strengthening and pathogen-eliminating in one prescription to achieve systemic therapeutic effects for early COVID-19 control and prevention.

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:

In this study we execute a rational screen to identify Chinese medical herbs that are commonly used in treating viral respiratory infections and also contain compounds that might directly inhibit 2019 novel coronavirus (2019-nCoV), an ongoing novel coronavirus that causes pneumonia.

Methods

There were two main steps in the screening process. In the first step we conducted a literature search for natural compounds that had been biologically confirmed as against sever acute respiratory syndrome coronavirus or Middle East respiratory syndrome coronavirus. Resulting compounds were cross-checked for listing in the Traditional Chinese Medicine Systems Pharmacology Database. Compounds meeting both requirements were subjected to absorption, distribution, metabolism and excretion (ADME) evaluation to verify that oral administration would be effective. Next, a docking analysis was used to test whether the compound had the potential for direct 2019-nCoV interaction. In the second step we searched Chinese herbal databases to identify treatments containing the selected compounds. Plants containing 2 or more of the compounds identified in our screen were then checked against the catalogue for classic herbal usage. Finally, network pharmacology analysis was used to predict the general in vivo effects of each selected herb.

Results

Of the natural compounds screened, 13 that exist in traditional Chinese medicines were also found to have potential anti-2019-nCoV activity. Further, 125 Chinese herbs were found to contain 2 or more of these 13 compounds. Of these 125 herbs, 26 are classically catalogued as treating viral respiratory infections. Network pharmacology analysis predicted that the general in vivo roles of these 26 treatments were related to regulating viral infection, immune/inflammation reactions and hypoxia response.

Conclusion

Chinese herbal treatments classically used for treating viral respiratory infection might contain direct anti-2019-nCoV compounds.

Objective

This study investigated the biochemical, histopathological and physiological effects of Citrullus colocynthis on peripheral neuropathy in rats with streptozotocin (STZ)-induced diabetes.

Methods

Seventy adult male Sprague-Dawley rats were included in the present study. Diabetes was induced in 60 rats, with a single intraperitoneal injection of STZ (65 mg/kg). After 4 weeks, the diabetic rats were assessed for neuropathy. Then, the diabetic rats with neuropathy were randomly divided into 6 groups for a 4-week treatment with gabapentin, oral administration of C. colocynthis fruit pulp powder (100 and 300 mg/kg per day), topical preparations as oil-based solution and ointment, or placebo. Changes in metabolic, physiological, biochemical and histological parameters were considered as treatment outcomes.

Results

Metabolic outcomes (body weight and blood glucose level) were improved in the C. colocynthis-treated groups as compared to placebo. Tail-flick and hot-plate tests also had lower latency in the C. colocynthis-treated groups. Measurement of oxidative stress markers (malondialdehyde, superoxide dismutase and catalase) showed the antioxidant effect of C. colocynthis. Histological evaluation of the sciatic nerve showed that C. colocynthis decreased the number of demyelinated and degenerated nerve fibers. Among the C. colocynthis-treated groups, the one receiving 100 mg/kg per day oral powder had the best treatment outcomes.

Conclusion

The present study showed that C. colocynthis fruit, through its antioxidant and hypoglycemic activities, has a positive effect in the treatment of diabetic neuropathy.