Multiple cutaneous carcinoma arising from arsenic-containing traditional Chinese medicine in a patient with psoriasis: A case report.

Background: Arsenic exposure is closely related to keratosis and cutaneous carcinoma, but a few studies have focused on patients with psoriasis presenting carcinoma after long-term medication of arsenic-containing traditional Chinese medicine (TCM). Case description: We presented a psoriasis patient showing multiple cutaneous carcinoma arising from arsenic containing TCM. A 60-year-old gentleman with psoriasis for nearly 30 years presented to our department with severe keratosis in hands, trunk and feet. He received oral administration of realgar (with As4S4 as the major component) for at least 15 years. There were keratotic plaques, ulcer and exudate in the middle finger and forefinger of left hand, and middle finger, forefinger and ring finger of the right hand. Moreover, brown papule was seen in right sole, together with keratotic plaques and ulcer in the left heel. Pathological analysis revealed basal cell carcinoma (BCC) in the anterior chest, right hand and right foot, Bowen disease in left hand and right hand, as well as squamous cell carcinomas (SCC) in right hand. Conclusion: This is a rare arsenic-exposure psoriasis patient showed coexistence of Bowen disease in left hand and right hand, BCC in the thoracic site, right hand and right foot, as well as SCC in right hand.

The efficacy and safety of Chinese herbal medicine in the treatment of painful diabetic neuropathy: A systematic review and meta-analysis.

Objective: The objective of this systematic review and meta-analysis is to assess the effectiveness and security of Chinese herbal medicine (CHM) in the therapy of painful diabetic neuropathy (PDN). Methods: We searched databases for randomized controlled trials (RCTs) of CHM in the treatment of PDN. Outcome indicators included nerve conduction velocity, clinical efficiency, pain score, TCM syndrome score, and adverse events. Stata 16.0 was used to carry out the Meta-analysis. Results: A total of 21 RCTs with 1,737 participants were included. This meta-analysis found that using CHM as adjuvant treatment or as monotherapy for PDN can improve SCV of median nerve [mean difference (MD) = 3.56, 95% Confidence interval (CI) (2.19, 4.92) ], MCV of median nerve [ MD = 3.82, 95% CI (2.51, 5.12) ], SCV of common peroneal nerve [ MD = 4.16, 95% CI (1.62, 6.70) ], MCV of common peroneal nerve [ MD = 4.37, 95% CI (1.82, 6.93) ], SCV of gastrocnemius nerve [ MD = 4.95, 95% CI (3.52, 6.37) ], SCV of tibial nerve [ MD = 3.17, 95% CI (-2.64, 8.99) ], MCV of tibial nerve [MD = 6.30, 95%CI (5.00, 7.60)] and clinical effective rate [ odds ratio (OR) = 4.00, 95% CI (2.89, 5.52) ] and reduce pain score [standardized mean difference (SMD) = -2.23, 95% CI (-3.04, -1.41) ], TCM syndrome score [ MD = -4.70, 95% CI (-6.61, -2.80) ]. In addition, compared to the control group, adverse events of Chinese medicine intervention occurred less. Conclusion: CHM as adjuvant therapy or single treatment has a good curative effect and is safe for patients with PDN, which is worthy of clinical promotion and use, however; higher quality clinical studies are still needed to prove. Systematic Review Registration: https://www.crd.york.ac.uk/, identifier CRD42022327967.

Epidemiological Investigation of 387 Individuals Over 65 Years Old With Osteoporotic Fractures.

Context: With the rapidly aging population globally, osteoporosis (OP) has become a major public health problem, and fracture is a common complication of OP. Older adults, especially postmenopausal women, have a higher incidence of OP. Objective: The study intended to analyze the clinical information, epidemiological characteristics, treatments, and follow-up results of patients with osteoporotic fractures (OPFs) in adults over 65 years old, to provide data support for the prevention, treatment, and use of OPF focus groups in clinical practice. Design: The research team performed a retrospective analysis using electronic medical records and related imaging data of patients. Setting: The study took place at Hebei General Hospital in Hebei, China. Participants: Participants were 387 patients over 65 years old with osteoporotic fractures who had been admitted to the hospital between July 2012 and July 2018. Outcome Measures: The research team recorded participants' ages, genders, fracture causes, and fracture sites. The team performed a follow-up analysis on refractures, treatment with anti-osteoporotic drugs, exercise, and survival status within the 3 years after surgery. Results: The study's male-to-female ratio was 1:3.1, and the rate of osteoporotic fracture for females was significantly higher than that of males. The mean age of participants with fractures was 75.6 ± 8.5 years, and most fractures occurred in participants 78 to 85 years old. Of the 387 participants, 169 participants had hip fractures (43.67%); 98 had vertebral compression fractures (25.32%); 51 had distal radius and ulna fractures (13.18%); 42 had proximal humerus fractures (10.85%); and 27 had other fractures (6.98%). The number of women with fractures at each site was greater than the number of men, but the differences weren't statistically significant (P > .05). The main causes of injury were falls (71.58%), and the main place of the occurrence of injury was at home (65.6%). Of the 387 participants, 346 had surgical treatment (89.41%), and the effective rate of surgical treatment was 99.42%. Three years after surgery, the research team followed up with 235 participants, for a follow-up rate of 60.72%. Within the 3 years of the follow-up period, 61 participants had refractures (25.63%), 29 received treatment with regular anti-osteoporotic drugs (12.34%), 36 exercised twice or more a week (15.32%), and 32 had died for various reasons (13.62%). Conclusions: The study preliminarily described the epidemiological characteristics of 387 osteoporotic fractures in adults over 65 years old. More women had fractures than men; the hip was the most common fracture site, and falls were the main cause of injury. Most of the fractures occurred in the place of residence, and the refracture rate was 25.96% at three years after surgery.

ER ribosomal-binding protein 1 regulates blood pressure and potassium homeostasis by modulating intracellular renin trafficking.

BACKGROUND: Genome-wide association studies (GWASs) have linked RRBP1 (ribosomal-binding protein 1) genetic variants to atherosclerotic cardiovascular diseases and serum lipoprotein levels. However, how RRBP1 regulates blood pressure is unknown. METHODS: To identify genetic variants associated with blood pressure, we performed a genome-wide linkage analysis with regional fine mapping in the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) cohort. We further investigated the role of the RRBP1 gene using a transgenic mouse model and a human cell model. RESULTS: In the SAPPHIRe cohort, we discovered that genetic variants of the RRBP1 gene were associated with blood pressure variation, which was confirmed by other GWASs for blood pressure. Rrbp1- knockout (KO) mice had lower blood pressure and were more likely to die suddenly from severe hyperkalemia caused by phenotypically hyporeninemic hypoaldosteronism than wild-type controls. The survival of Rrbp1-KO mice significantly decreased under high potassium intake due to lethal hyperkalemia-induced arrhythmia and persistent hypoaldosteronism, which could be rescued by fludrocortisone. An immunohistochemical study revealed renin accumulation in the juxtaglomerular cells of Rrbp1-KO mice. In the RRBP1-knockdown Calu-6 cells, a human renin-producing cell line, transmission electron and confocal microscopy revealed that renin was primarily retained in the endoplasmic reticulum and was unable to efficiently target the Golgi apparatus for secretion. CONCLUSIONS: RRBP1 deficiency in mice caused hyporeninemic hypoaldosteronism, resulting in lower blood pressure, severe hyperkalemia, and sudden cardiac death. In juxtaglomerular cells, deficiency of RRBP1 reduced renin intracellular trafficking from ER to Golgi apparatus. RRBP1 is a brand-new regulator of blood pressure and potassium homeostasis discovered in this study.

Effect of the polyphenol-rich extract from Allium cepa on hyperlipidemic sprague-dawley rats.

Allium cepa is used for the prevention and treatment of hyperlipidemia-related diseases such as atherosclerosis in the folk. This study was mainly aimed at investigating the effects of A. cepa extract (ACE) enriched in polyphenols on hyperlipidemia Sprague-Dawley (SD) experiment rat models. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), malondialdehyde (MDA), and superoxide dismutase (SOD) activity in serum and liver were measured using ELISA kits. In addition, hematoxylin-eosin (HE) technique was used to observe the liver and the aortic arch pathology. Moreover, western blotting (WB) method was applied to analyze LDL receptor (LDLR) and 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase (HMGCR) in liver. As a result, quercetin (2.42 mg/g DW) and isoquercitrin (4.60 mg/g DW) were the main constituents of ACE using HPLC analysis. Furthermore, ACE reduced the levels of TC, TG, LDL-C, and MDA, and increased HDL levels and elevated SOD activity both in serum and liver in hyperlipidemic SD rats (p < .05). HE results showed that liver fat drops of the rats in ACE group were obviously decreased, and the lipid and foam cells of the aortic arch of the rats in ACE group were markedly ameliorated. WB results showed that ACE promoted the degradation of HMGCR and increased LDLR expression in liver (p < .05). In conclusion, ACE alleviated hyperlipidemia with downregulation of HMGCR and upregulation of LDLR. PRACTICAL APPLICATIONS: Atherosclerosis, a major cardiovascular disease, is the leading cause of mortality and morbidity in the developed countries. Moreover, accumulating data indicate that, during atherosclerosis development, hyperlipidemia is an important risk factor. To date, hyperlipidemia is mainly treated with hyperlipidemic agents including statins, in spite of the side effects and poor tolerance in some patients. In addition, Allium cepa is a medicinal and edible plant. Furthermore, A. cepa is used for the prevention and treatment of hyperlipidemia-related diseases such as atherosclerosis in the folk. But the underlying mechanism is still unclear. In fact, this research showed that A. cepa extract (ACE) alleviated hyperlipidemia with downregulation of HMGCR and upregulation of LDLR, suggesting that ACE might be a potential option for hyperlipidemia as non-statin lipid-lowering agent.

Relative Bioavailability of Silybin A and Silybin B From 2 Multiconstituent Dietary Supplement Formulations Containing Milk Thistle Extract: A Single-dose Study.

PURPOSE: The purpose of this study was to compare the bioavailability between 2 milk thistle-containing dietary supplements, Product B and IsaGenesis, in healthy volunteers. METHODS: Bioavailability between Product B, originally formulated as a powdered capsule, and IsaGenesis, reformulated as a soft gel, were compared by measuring silybin A and silybin B as surrogate pharmacokinetic markers for differences in absorption and bioavailability. For this randomized, open-label, crossover pharmacokinetic study, 12 healthy volunteers consumed a single-dose serving of each supplement separated by at least a 7-day washout period. Serial blood samples were obtained at 0, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours and analyzed via LC-MS/MS. FINDINGS: Rapid absorption and elimination of silybin A and silybin B have been observed after oral administration of both Product B and IsaGenesis. However, the absorption rate and extent, as indicated by mean the Cmax and mean plasma AUC, were significantly higher for the IsaGenesis soft gel formulation. The dose-corrected mean Cmax was 365% and 450% greater for silybin A and B, respectively, relative to powdered Product B. The time to Tmax was reached, on average, at least 1 hour earlier with IsaGenesis relative to Product B for both silybin A and silybin B. IMPLICATIONS: The IsaGenesis soft gel formulation provided substantially greater absorption and bioavailability of silybin A and silybin B relative to the powdered Product B supplement. ClinicalTrials.gov Identifier: NCT02529605.

Tissue distribution of capilliposide B, capilliposide C and their bioactive metabolite in mice using liquid -tandem mass spectrometry.

Lysimachia capillipes Hemsl (Primulaceae), a folk medicinal plant in China, showed significant anti-tumor activities in vivo and in vitro. Capilliposide B (LC-B) and capilliposide C (LC-C) are the main bioactive components in this plant. To explore their tissue distribution, a reliable bioanalytical method for the quantification of LC-B, LC-C and their bioactive metabolite, capilliposide A (LC-A), in mouse tissues was developed and validated. In this study, the tissue distribution profiles of the three compounds were examined after intravenous administration of pure LC-B and oral administration of total saponins of L. capillipes Hemsl extract (LCE) for 10 days. Method validation was conducted over the curve range 10.0-5000 ng/mL for all three analytes in various tissue homogenates. The relative standard deviation of intra-day and inter-day precision of the QC samples was <14.7%, and the accuracy ranged from 85.9 to 114.0%. The results indicated that LC-B was rapidly and widely distributed throughout the whole body except for muscle following intravenous administration of LC-B. In addition, LC-A was only in liver, intestine, lung and stomach. After oral administration of LCE, LC-B and LC-C were distributed into various tissues. The highest levels were observed in stomach and intestine.

Liraglutide protects pancreatic beta cells during an early intervention in Gato-Kakizaki rats.

BACKGROUND: Glucagon-like peptide-1 (GLP-1) analogues have emerged as insulin secretagogues and are widely used in type 2 diabetic patients. GLP-1 analogues also demonstrate a promotion of beta cell proliferation and reduction of apoptosis in rodents. In the present study, we investigated the protection of pancreatic beta cells by early use (at the age of 2 weeks) of GLP-1 analogue, liraglutide in Gato-Kakizaki (GK) rats and explored the underlying mechanisms. METHODS: The effects of liraglutide on glucose tolerance were evaluated by intraperitoneal glucose tolerance test (IPGTT) and insulin release tests (IRT). Ki67 and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) immunostaining, Western blots and real-time polymerase chain reaction were applied to evaluate cell proliferation, apoptosis and related gene expressions. RESULTS: Our results demonstrated that early use of liraglutide improved glucose tolerance during liraglutide treatment in GK rats. Liraglutide increased pancreatic insulin contents and markedly reduced beta cell apoptosis. Liraglutide also downregulated pro-apoptotic gene expressions and reduced intra-islet macrophage infiltration. CONCLUSIONS: This experiment reported for the first time that early use of liraglutide could protect beta cell failure in pre-diabetic GK rats through reduction of beta cell apoptosis and ameliorating islet inflammation.