Chinese herbal medicine decreases incidence of hepatocellular carcinoma in diabetes mellitus patients with regular insulin management.

BACKGROUND: Type 2 diabetes mellitus (DM) is an independent risk factor for hepatocellular carcinoma (HCC), while insulin is a potent mitogen. Identifying a new therapeutic modality for preventing insulin users from developing HCC is a critical goal for researchers. AIM: To investigate whether regular herbal medicine use can decrease HCC risk in DM patients with regular insulin control. METHODS: We used data acquired from the Taiwanese National Health Insurance research database between 2000 and 2017. We identified patients with DM who were prescribed insulin for > 3 months. The herb user group was further defined as patients prescribed herbal medication for DM for > 3 months per annum during follow-up. We matched the herb users to nonusers at a 1:3 ratio according to age, sex, comorbidities and index year by propensity score matching. We analyzed HCC incidence, HCC survival rates, and the herbal prescriptions involved. RESULTS: We initially enrolled 657144 DM patients with regular insulin use from 2000 to 2017. Among these, 46849 patients had used a herbal treatment for DM, and 140547 patients were included as the matched control group. The baseline variables were similar between the herb users and nonusers. DM patients with regular herb use had a 12% decreased risk of HCC compared with the control group [adjusted hazard ratio (aHR) = 0.88, 95%CI = 0.80-0.97]. The cumulative incidence of HCC in the herb users was significantly lower than that of the nonusers. Patients with a herb use of > 5 years cumulatively exhibited a protective effect against development of HCC (aHR = 0.82, P < 0.05). Of patients who developed HCC, herb users exhibited a longer survival time than nonusers (aHR = 0.78, P = 0.0001). Additionally, we report the top 10 herbs and formulas in prescriptions and summarize the potential pharmacological effects of the constituents. Our analysis indicated that Astragalus propinquus (Huang Qi) plus Salvia miltiorrhiza Bunge (Dan Shen), and Astragalus propinquus (Huang Qi) plus Trichosanthes kirilowii Maxim. (Tian Hua Fen) were the most frequent combination of single herbs. Meanwhile, Ji Sheng Shen Qi Wan plus Dan Shen was the most frequent combination of herbs and formulas. CONCLUSION: This large-scale retrospective cohort study reveals that herbal medicine may decrease HCC risk by 12% in DM patients with regular insulin use.

Roles of conventional and complementary therapies in recurrent hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common type of cancer and the fourth leading cause of cancer-related deaths in the world. HCC has a reported recurrence rate of 70%-80% after 5 years of follow-up. Controlling tumor recurrence is the most critical factor associated with HCC mortality. Conventional salvage therapies for recurrent HCC include re-hepatectomy or liver transplantation, transcatheter arterial chemoembolization, Y-90, target therapy, and immunotherapy; however, these conventional treatment modalities have yet to achieve consistently favorable outcomes. Meanwhile, previous studies have demonstrated that conventional therapies in combination with traditional Chinese medicine (TCM), acupuncture, moxibustion or dietary supplements could notably benefit patients with HCC recurrence by strengthening and augmenting the overall management strategy. However, systemic reviews related to the interactions between complementary therapies and conventional therapy in recurrent HCC are limited. In this review, we discuss the molecular mechanisms underlying the functions of complementary therapies for recurrent HCC, which include augmenting the local control to improve the congestion status of primary tumors and reducing multicentric tumor occurrence via inducing autophagy, apoptosis or cell cycle arrest. TCM and its derivatives may play important roles in helping to control HCC recurrence by inhibiting epithelial-mesenchymal transition, migration, invasion, and metastasis, inhibiting cancer stem cells, and ameliorating drug resistance.

Scutellaria barbata D. Don Inhibits the Main Proteases (Mpro and TMPRSS2) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.

In late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic emerged to severely impact the global population, creating an unprecedented need for effective treatments. This study aims to investigate the potential of Scutellaria barbata D. Don (SB) as a treatment for SARS-CoV-2 infection through the inhibition of the proteases playing important functions in the infection by SARS-CoV-2. FRET assay was applied to investigate the inhibitory effects of SB on the two proteases involved in SARS-CoV-2 infection, Mpro and TMPRSS2. Additionally, to measure the potential effectiveness of SB treatment on infection inhibition, cellular models based on the Calu3 and VeroE6 cells and their TMPRSS2- expressing derivatives were assessed by viral pseudoparticles (Vpp) infection assays. The experimental approaches were conjugated with LC/MS analyses of the aqueous extracts of SB to identify the major constituent compounds, followed by a literature review to determine the potential active components of the inhibitory effects on protease activities. Our results showed that SB extracts inhibited the enzyme activities of Mpro and TMPRSS2. Furthermore, SB extracts effectively inhibited SARS-CoV-2 Vpp infection through a TMPRSS2-dependent mechanism. The aqueous extract analysis identified six major constituent compounds present in SB. Some of them have been known associated with inhibitory activities of TMPRSS2 or Mpro. Thus, SB may effectively prevent SARS-CoV-2 infection and replication through inhibiting Mpro and TMPRSS2 protease activities.

Principles and treatment strategies for the use of Chinese herbal medicine in patients at different stages of coronavirus infection.

Coronavirus disease 2019 (COVID-19) is a novel, human-infecting ß-coronavirus enveloped, positive-sense single-stranded RNA viruses, similar to the severe acute respiratory syndrome (SARS) infection that emerged in November 2002. In traditional Chinese medicine (TCM), the epidemic disease concepts of "febrile epidemics" (wenyi) or "warm diseases" (wenbing) are based on geographic and cultural aspects, and Chinese herbal medicine (CHM) played an important role in the treatment of epidemic diseases. CHM was widely used to treat patients suffered with SARS almost two decades ago during outbreak of SARS, with proven safety and potential benefits. TCM has also been widely used to treat cancer patients for a long history and much of them associate with immunomodulatory activity and are used to treat coronavirus-related diseases. We propose the use of CHM treatment principles for clinical practice, based on four main stages of COVID-19 infection: early, intermediate, severe, and convalescence. We suggest corresponding decoctions that exhibit antiviral activity and anti-inflammatory effects in the early stage of infection; preventing the disease from progressing from an intermediate to severe stage of infection; restoring normal lung function and improving consciousness in the severe stage; and ameliorating pulmonary and vascular injury in the convalescent stage. We summarize the pharmaceutical mechanisms of CHM for treating coronavirus via antiviral, anti-inflammatory and immunomodulatory effects.

Signal Transduction Pathways of Acupuncture for Treating Some Nervous System Diseases.

In this article, we review signal transduction pathways through which acupuncture treats nervous system diseases. We electronically searched the databases, including PubMed, MEDLINE, clinical Key, the Cochrane Library, and the China National Knowledge Infrastructure from their inception to December 2018 using the following MeSH headings and keywords alone or in varied combination: acupuncture, molecular, signal transduction, genetic, cerebral ischemic injury, cerebral hemorrhagic injury, stroke, epilepsy, seizure, depression, Alzheimer's disease, dementia, vascular dementia, and Parkinson's disease. Acupuncture treats nervous system diseases by increasing the brain-derived neurotrophic factor level and involves multiple signal pathways, including p38 MAPKs, Raf/MAPK/ERK 1/2, TLR4/ERK, PI3K/AKT, AC/cAMP/PKA, ASK1-JNK/p38, and downstream CREB, JNK, m-TOR, NF-κB, and Bcl-2/Bax balance. Acupuncture affects synaptic plasticity, causes an increase in neurotrophic factors, and results in neuroprotection, cell proliferation, antiapoptosis, antioxidant activity, anti-inflammation, and maintenance of the blood-brain barrier.

Acupuncture-Analgesia-Mediated Alleviation of Central Sensitization.

Pain can trigger central amplification called central sensitization, which ultimately results in hyperalgesia and/or allodynia. Many reports have showed acupuncture has an analgesic effect. We searched the related article on PubMed database and Cochrane database to discover central sensitization pathway in acupuncture analgesia. We summarized that acupuncture enhances the descending inhibitory effect and modulates the feeling of pain, thus modifying central sensitization. The possible mechanisms underlying the analgesic effects of acupuncture include segmental inhibition and the activation of the endogenous opioid, adrenergic, 5-hydroxytryptamine, and N-methyl-D-aspartic acid, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate pathways. Moreover, acupuncture can locally reduce the levels of inflammatory mediators. In clinical settings, acupuncture can be used to treat headache, neuropathic pain, low back pain, osteoarthritis, and irritable bowel syndrome. These mechanisms of acupuncture analgesia may be involved in the alleviation of central sensitization.

Chinese herbal medicine to treat urolithiasis in a patient with right flank pain and hematuria: A case report.

OBJECTIVE: Urolithiasis is a common medical condition affecting the urinary tract. Typical symptoms reported by patients include colic pain and hematuria. Some patients may undergo surgical intervention or lithotripsy to remove the stones. In this case, we demonstrated that Chinese herbal medicine (CHM) was an effective modality to remove stones in a patient with urolithiasis. CLINICAL FEATURES AND OUTCOME: A 47-year-old man suffered from right flank pain and hematuria for three months and was diagnosed with an upper third ureteral stone obstruction with right hydronephrosis. He had received extracorporeal shock wave lithotripsy (ESWL) three times before his first CHM visit, but it was unsuccessful. Therefore, he sought CHM for further intervention. His symptoms subsided, and the image study showed complete removal of the ureteral stone after regular therapy with Zhi Bai Di Huang Wan () combined with Lygodii spora (), Curcumae radix (), Endothelium Corneum Gigeriae Galli (), Lysimachiae herba (), Orthosiphon stamineus () for approximately four months. Neither complications nor side-effects were noted during the CHM treatment. CONCLUSIONS: In this case, we concluded that CHM may be an effective alternative therapy for the treatment of ureteral stones, and furthermore, may also be applied as an option to salvage failed ESWL procedures.