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.

LipoCol Forte capsules reduce the risk of liver cancer: A propensity score-matched, nationwide, population-based cohort study.

BACKGROUND: Liver cancer is among the top five most common cancers globally. Lipid-lowering drugs such as statins can lower the risk of liver cancer, but may also cause liver damage. LipoCol Forte capsules (LFC), a red yeast rice product, have demonstrated significant antihypercholesterolemic effects and a good safety profile in clinical studies. AIM: To evaluate whether LFC lowers the risk of liver cancer in adults in this propensity score-matched, nationwide, population-based cohort study. METHODS: We used data from Taiwan's National Health Insurance Research Database, which includes electronic medical records for up to 99.99% of Taiwan's population. LFC users and LFC non-users were matched 1:1 by propensity scores between January 2010 and December 2017. All had follow-up data for at least 1 year. Statistical analyses compared demographic distributions including sex, age, comorbidities, and prescribed medications. Cox regression analyses estimated adjusted hazard ratios (aHRs) after adjusting for potential confounders. RESULTS: We enrolled 33231 LFC users and 33231 non-LFC users (controls). No significant differences between the study cohorts were identified regarding comorbidities and medications [standardized mean difference (SMD) < 0.05]. At follow-up, the overall incidence of liver cancer was significantly lower in the LFC cohort compared with controls [aHR 0.91; 95% confidence interval (CI): 0.86-0.95; P < 0.001]. The risk of liver cancer was significantly reduced in both females (aHR 0.87; 95%CI: 0.8-0.94; P < 0.001) and males (aHR 0.93; 95%CI: 0.87-0.98; P < 0.01) in the LFC cohort compared with their counterparts in the non-LFC cohort. The antitumor protective effects applied to patients with comorbidities (including hypertension, ischemic stroke, diabetes mellitus, hyperlipidemia, hepatitis B infection and hepatitis C infection). Those using LFC for more than 84 drug days had a 0.64-fold lower risk of liver cancer compared with controls (P < 0.001). Compared with controls, the risk of developing liver cancer in the LFC cohort progressively decreased over time; the lowest incidence of liver cancer occurred in LFC users followed-up for more than 6 years (27.44 vs 31.49 per 1,000 person-years; aHR 0.75; 95%CI: 0.68-0.82; P < 0.001). CONCLUSION: This retrospective cohort study indicates that LFC has a significantly protective effect on lowering the risk of liver cancer, in a dose-dependent and time-dependent manner.

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.

ABO blood type and clinical characteristics of patients with ulcerative colitis: A hospital-based study in central Taiwan.

BACKGROUND: The variations in ABO blood groups are reported to be associated with multiple disorders, including ulcerative colitis (UC). We aimed to investigate the distribution of ABO blood groups in UC patients and explore its impact on disease severity. METHODS: We retrospectively collected 129 UC patients diagnosed at our hospital between January 2000 and November 2019. Clinical characteristics, ABO blood groups, and operation rates were analyzed. RESULTS: The mean diagnostic age of patients was 38.97 years. Males accounted for the majority of all patients (62.8%). Of 129 patients, 43 (33.3%) were blood type O, 41 (31.8%) were blood type A, 38 (29.5%) were blood type B, and 7 (5.4%) were blood type AB. Although our patients had higher ratio of blood type A comparing our general population, there was no statistically significant association of ABO blood types distribution between these two groups (p = 0.1906). In the subgroup analysis, there were no significant difference of disease locations and operation rates between different ABO blood groups. Furthermore, blood type A patients had higher serum hemoglobin (Hb) levels compared to blood type O patients (13.31 g/dL vs. 12.30 g/dL, p = 0.0347). Blood type A patients had lower serum erythrocyte sedimentation rate (ESR) levels compared to blood type O patients (12.46 mm/hour vs. 21.5 mm/hour, p = 0.0288). Blood type O had higher serum ESR levels compared to non-O groups (p = 0.0228). In the ABO blood groups and mean diagnostic age (≤ 40 years or > 40 years), there were no statistically significant difference between these two age groups, p = 0.5515. CONCLUSIONS: Our results showed ABO blood groups are not associated with UC in spite of a higher ratio of blood type A in our patients. Blood type O patients had higher serum ESR levels; however, blood type A patients had higher Hb levels.

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.

Adverse Gastrointestinal Effects with Kayexalate or Kalimate: A Comprehensive Review.

BACKGROUND: Patients with hyperkalemia are commonly treated with Kayexalate or Kalimate. Both drugs are associated with some fatal gastrointestinal (GI) adverse events (AEs). AIM: To assess the clinical characteristics and outcomes of GI AEs induced by Kayexalate or Kalimate from published case reports. METHODS: We conducted a systematic review of case reports of Kayexalate or Kalimate-induced GI AEs, from PubMed, Medline, Cochrane Library, Clinical Key, and Google Scholar databases (1948 to March 31, 2020). We analyzed the clinical characteristics, GI AEs, and risk factors of enrolled patients. RESULTS: We identified 41 published articles describing 135 cases of GI AEs induced by Kayexalate (103 cases) or Kalimate (32 cases). The mean age of all patients was 55.5 years. Most patients were male (54.8%). As high as 55.6% preparations were administered with sorbitol whereas 44.4% preparations had no sorbitol. The average time causing GI AEs was 19.8 days. Colon was the most commonly affected site (76.3%). Drug crystals were histopathologically proven in 95.5% of the patients. Meanwhile, mortality was reported in 20.7%. CONCLUSION: Kayexalate or Kalimate, without or with sorbitol combination, may be related to fatal GI damage. Uremia, hypertension, and transplantation are predisposing factors. Clinicians should be careful in prescribing Kayexalate or Kalimate to patients.

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.

Irritable bowel syndrome increases the risk of chronic obstructive pulmonary disease: A retrospective cohort study.

Both inflammation and infection are associated with the development of irritable bowel syndrome (IBS) and chronic obstructive pulmonary disease (COPD). The purpose of this study is to further elucidate the association between IBS and COPD through a retrospective cohort study. We enrolled IBS patients diagnosed between 2000 and 2011 with follow-up for at least one year. The non-IBS patients as comparison group were selected with 1:3 matching by propensity score. Statistical analysis was utilized to assess the differences in characteristic distribution, and to compare the cumulative incidence of COPD between the IBS and non-IBS cohorts. We selected 14,021 IBS patients and 42,068 non-IBS patients for comparison. The IBS patients exhibited a significant risk to develop COPD compared with non-IBS patients. Additionally, the cumulative incidence rate of COPD in the IBS cohort increased significantly during the follow-up period of more than ten years, compared to the non-IBS cohort, based on the Kaplan-Meier analysis. The risk of COPD was also significantly decreased in those patients with more than eighteen IBS-related clinical visits. This retrospective cohort study demonstrates the significantly increased risk of COPD in patients with IBS. Therefore, early inspection and prevention of COPD is essential for patients with IBS.

QuantiFERON-TB Gold Test Conversion Is Associated with Active Tuberculosis Development in Inflammatory Bowel Disease Patients Treated with Biological Agents: An Experience of a Medical Center in Taiwan.

Taiwan has a lower prevalence of inflammatory bowel disease (IBD) and a higher prevalence of tuberculosis (TB) infection than Western countries. The aim of this study was to investigate the prevalence of latent TB (LTB) and active TB infection in IBD patients treated with biological agents. From January 2000 to September 2018, we retrospectively collected data from IBD patients treated with biological agents at a tertiary referral center. Patients underwent a QuantiFERON-TB Gold test (QFT) to screen for TB infection before and after biological treatment courses. The diagnostic age, sex, body mass index, hepatitis B virus infection, biochemistry profile, treatment regimens, and the results of the QFT were analyzed. Overall, 130 IBD patients who received biological treatment were enrolled. The results of the QFT before biological treatment were determined in 120 patients (92%); of these, 10 were positive (8%), 110 were negative (85%), and 10 were indeterminate (9%). Six patients demonstrated seroconversion after biological treatment, as determined by the QFT. Three patients (2.4%) developed active pulmonary TB after biological treatment. In subgroup analysis, the positive QFT patients had a trend of lower baseline serum C-reactive protein and erythrocyte sedimentation rate levels than the negative QFT group. The present study demonstrates that the prevalence of LTB before and after biological treatment is higher in Taiwan than in most Western countries and similar to other Asian countries. Therefore, screening and monitoring of TB infection are necessary for IBD patients before and during biological treatments in Taiwan.

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.

Epidemiology and Clinical Outcomes of Inflammatory Bowel Disease: A Hospital-Based Study in Central Taiwan.

The incidence and prevalence of inflammatory bowel disease (IBD) are low but increasing in Taiwan. We aimed to investigate the epidemiology and clinical outcomes of IBD in central Taiwan. We retrospectively analyzed patients with IBD diagnosed at our hospital between January 2000 and September 2018. The diagnostic criteria were based on endoscopic and pathologic findings. Clinical characteristics, treatment regimens, and treatment outcomes were analyzed. A total of 190 patients with IBD were enrolled (80 with Crohn's disease (CD) and 110 with ulcerative colitis (UC)). The mean age at diagnosis was 38.4 years (CD: 36 years, UC: 40 years). Male patients accounted for the majority of patients (71.1%). The male-to-female ratio was 3 : 1 for CD and 2.1 : 1 for UC. Current and ever smokers accounted for 30.5% of all patients. Only 4.2% of patients had a family history of IBD. Extraintestinal manifestations (EIMs) were reported in 7.9%, and colorectal cancers (CRCs) were reported in 2.1% of all patients. In patients with CD, the ileal type was the most common disease phenotype (57.5%), and the stricturing type was the most common disease behavior (60.0%). In patients with UC, left-sided colitis was the predominant disease extent (42.7%). The seroprevalence of hepatitis B virus (HBV) was 13.3%. The incidence of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) in patients with UC was 22%. 5-Aminosalicylic acids were the preferred treatment for UC, whereas corticosteroids, immunomodulators, and biologic agents were preferred for CD. In patients with CD, the bowel resection rate was 38.8%, and the incidence of hip avascular necrosis was 3.8%. In Taiwan, patients with IBD showed a male predominance, lack of familial clustering, a higher prevalence of HBV infection, and a lower prevalence of p-ANCA, EIMs, and CRC. Moreover, a higher incidence of the ileal type with poor outcomes of CD and left-sided predominance in UC were found.

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.