An arteriovenous fistula model: Carotid artery-posterior facial vein fistula in rats.

OBJECTIVE: To describe an alternative arteriovenous fistula (AVF) model involving anastomosis of the common carotid artery (CCA) with the posterior facial vein (PFV). METHODS: Twenty-two male Sprague-Dawley rats (age 6-8 weeks) were used to establish the AVF model involving end-to-side anastomosis of PFV and CCA. The peak velocity of the CCA and the diameter of the outflow vein were recorded at 7, 14, and 42 days after the operation using Doppler ultrasound. Pathological examination of the intimal lesions was performed at 14 and 42 days after operation. RESULTS: One rat died within 24 h after surgery related to anesthesia. The patency rates at days 7, 14, and 42 were 85.7%, 81%, and 81%, respectively. The diameter of the carotid artery in rats is approximately 0.8 mm. The diameter of the outflow vein was increased by 1.7-fold and 2.2-fold at 7 days (1.1 ± 0.118 mm) and 14 days (1.4 ± 0.073 mm). At 42 days (1.96 ± 0.101 mm) after operation, the diameter was 3-fold greater compared to the unoperated control rat. The peak systolic flow velocity of the carotid artery at 7 days (593 ± 17.36 mm/s) and 14 days (767 ± 13.64 mm/s) after surgery was significantly greater compared to the control rat (314 ± 15.13 mm/s). The rate of increase was fastest at 7 days and leveled off from 14 to 42 days (875 ± 26 mm/s) after surgery. At 14 days, the intima area showed a nearly 50-fold increase (230 ± 9.93 µm2 × 103) compared to control (area 5 ± 0.37 µm2 × 103). Comparing 6 weeks with 2 weeks (280 ± 10.54 µm2 × 103) after surgery, the intima area increased 1.2 times. CONCLUSION: The CCA-PFV fistula in rats is a viable alternative AVF model.

Myricitrin inhibited ferritinophagy-mediated ferroptosis in cisplatin-induced human renal tubular epithelial cell injury.

Cisplatin-induced acute kidney injury (AKI) increases the patient mortality dramatically and results in an unfavorable prognosis. A strong correlation between AKI and ferroptosis, which is a notable type of programmed cell death, was found in recent studies. Myricitrin is a natural flavonoid compound with diverse pharmacological properties. To investigate the protective effect of myricitrin against cisplatin induced human tubular epithelium (HK-2) cell injury and the underlying anti-ferroptic mechanism by this study. Firstly, a pharmacology network analysis was proposed to explore the myricitrin's effect. HK-2 cells were employed for in vitro experiments. Ferroptosis was detected by cell viability, quantification of iron, malondialdehyde, glutathione, lipid peroxidation fluorescence, and glutathione peroxidase (GPX4) expression. Ferritinophagy was detected by related protein expression (NCOA4, FTH, LC3II/I, and SQSTM1). In our study, GO enrichment presented that myricitrin might be effective in eliminating ferroptosis. The phenomenon of ferroptosis regulated by ferritinophagy was observed in cisplatin-activated HK-2 cells. Meanwhile, pretreatment with myricitrin significantly rescued HK-2 cells from cell death, reduced iron overload and lipid peroxidation biomarkers, and improved GPX4 expression. In addition, myricitrin downregulated the expression of LC3II/LC3I and NCOA4 and elevated the expression of FTH and SQTM. Furthermore, myricitrin inhibited ROS production and preserved mitochondrial function with a lower percentage of green JC-1 monomers. However, the protection could be reserved by the inducer of ferritinophagy rapamycin. Mechanically, the Hub genes analysis reveals that AKT and NF-κB are indispensable mediators in the anti-ferroptic process. In conclusion, myricitrin ameliorates cisplatin induced HK-2 cells damage by attenuating ferritinophagy mediated ferroptosis.

The role of ferroptosis in DM-induced liver injury.

The liver damage caused by Diabetes Mellitus (DM) has attracted increasing attention in recent years. Liver injury in DM can be caused by ferroptosis, a form of cell death caused by iron overload. However, the role of iron transporters in this context is still not clear. Herein, we attempted to shed light on the pathophysiological mechanism of ferroptosis. DM was induced in 8-week-old male rats by streptozotocin (STZ) before assessment of the degree of liver injury. Together with histopathological changes, variations in glutathione peroxidase 4 (GPX4), glutathione (GSH), superoxide dismutase (SOD), transferrin receptor 1 (TFR1), ferritin heavy chain (FTH), ferritin light chain (FTL), ferroportin and Prussian blue staining, were monitored in rat livers before and after treatment with Fer-1. In the liver of STZ-treated rats, GSH and SOD levels decreased, whereas those of malondialdehyde (MDA) increased. Expression of TFR1, FTH and FTL increased whereas that of glutathione peroxidase 4 (GPX4) and ferroportin did not change significantly. Prussian blue staining showed that iron levels increased. Histopathology showed liver fibrosis and decreased glycogen content. Fer-1 treatment reduced iron and MDA levels but GSH and SOD levels were unchanged. Expression of FTH and FTL was reduced whereas that of ferroportin showed a mild decrease. Fer-1 treatment alleviated liver fibrosis, increased glycogen content and mildly improved liver function. Our study demonstrates that ferroptosis is involved in DM-induced liver injury. Regulating the levels of iron transporters may become a new therapeutic strategy in ferroptosis-induced liver injury.

Effect of acupuncture on ischaemic stroke in patients with rheumatoid arthritis: a nationwide propensity score-matched study.

OBJECTIVE: To demonstrate that acupuncture is beneficial for decreasing the risk of ischaemic stroke in patients with rheumatoid arthritis (RA). DESIGN: A propensity score-matched cohort study. SETTING: A nationwide population-based study. PARTICIPANTS: Patients with RA diagnosed between 1 January 1997 and 31 December 2010, through the National Health Insurance Research Database in Taiwan. INTERVENTIONS: Patients who were administered acupuncture therapy from the initial date of RA diagnosis to 31 December 2010 were included in the acupuncture cohort. Patients who did not receive acupuncture treatment during the same time interval constituted the no-acupuncture cohort. PRIMARY OUTCOME MEASURES: A Cox regression model was used to adjust for age, sex, comorbidities, and types of drugs used. We compared the subhazard ratios (SHRs) of ischaemic stroke between these two cohorts through competing-risks regression models. RESULTS: After 1:1 propensity score matching, a total of 23 226 patients with newly diagnosed RA were equally subgrouped into acupuncture cohort or no-acupuncture cohort according to their use of acupuncture. The basic characteristics of these patients were similar. A lower cumulative incidence of ischaemic stroke was found in the acupuncture cohort (log-rank test, p<0.001; immortal time (period from initial diagnosis of RA to index date) 1065 days; mean number of acupuncture visits 9.83. In the end, 341 patients in the acupuncture cohort (5.95 per 1000 person-years) and 605 patients in the no-acupuncture cohort (12.4 per 1000 person-years) experienced ischaemic stroke (adjusted SHR 0.57, 95% CI 0.50 to 0.65). The advantage of lowering ischaemic stroke incidence through acupuncture therapy in RA patients was independent of sex, age, types of drugs used, and comorbidities. CONCLUSIONS: This study showed the beneficial effect of acupuncture in reducing the incidence of ischaemic stroke in patients with RA.

The Association between Acupuncture Therapy and the Risk of Disability Development in Dementia Patients: A Nationwide Cohort Study.

Purpose: Disability is the comorbidity of dementia for which there is no available preventive measure. The aim of this study was to investigate the association between acupuncture treatment and the risk of disability development in dementia patients. Patients and Methods: A cohort study was performed using a nationwide health database in Taiwan. The included dementia patients were divided into acupuncture and non-acupuncture cohorts based on whether they received acupuncture treatment during the follow-up period. The variables in the two cohorts were controlled by 1:1 propensity-score matching. The difference in disability development in dementia patients between the acupuncture and non-acupuncture cohorts was also analyzed. Subgroup analyses were performed using socioeconomic variables, comorbidities and anti-dementia agents (donepezil, rivastigmine, galantamine and memantine) used for dementia treatment. Results: A total of 9,760 dementia patients met our inclusion criteria, and patients were divided into an equal number (n=2,422) of acupuncture and non-acupuncture groups, respectively, after 1:1 propensity-score matching. The dementia patients had a lower risk of disability development after acupuncture treatment than those who did not receive acupuncture treatment (adjusted hazard ratio 0.65, 95% confidence interval 0.60-0.70, p < 0.001). The results were independent of basic variables or comorbidities in the two cohorts. Patients who did not use anti-dementia agents had a lower risk of developing disability after receiving acupuncture intervention than those who used anti-dementia agents. Conclusion: Our results revealed the relationship between acupuncture intervention and decreased risk of developing disability in dementia patients. The results are useful for dementia treatment, trial design and further planning of care programs.

The association between acupuncture therapy and the risk of reduced pressure ulcers in dementia patients: A retrospective matched cohort study.

Background: The pressure ulcer is a complication developed from dementia. The aim of this study is to study the association between the development of pressure ulcers and the use of acupuncture therapy in patients with dementia. Methods: We performed a retrospective 1:1 propensity score-matched cohort study to investigate the association between acupuncture therapy and the risk of pressure ulcers in patients with dementia. Results: A total of 8,994 patients were identified, 237 patients in the acupuncture cohort and 362 patients in the no-acupuncture cohort developed pressure ulcers. A reduced cumulative incidence of pressure ulcers was observed in the acupuncture cohort (P<0.001). The association between acupuncture and reducing the incidence of pressure ulcers was not affected by sex, age, residence, income, or comorbidities. The variables of etiologies to cause dementia did not change the final result. In the subgroups analyses, the patients without medication for dementia control had a significantly lower rate of pressure ulcers development when they had accepted acupuncture therapy (log-rank test, P<0.001). Conclusion: Our results revealed the association between acupuncture therapy and a reduced incidence of pressure ulcer development in patients with dementia. This finding offers important ideas for further research.

Low Ruthenium Content Confined on Boron Carbon Nitride as an Efficient and Stable Electrocatalyst for Acidic Oxygen Evolution Reaction.

To date, only a few noble metal oxides exhibit the required efficiency and stability as oxygen evolution reaction (OER) catalysts under the acidic, high-voltage conditions that exist during proton exchange membrane water electrolysis (PEMWE). The high cost and scarcity of these catalysts hinder the large-scale application of PEMWE. Here, we report a novel OER electrocatalyst for OER comprised of uniformly dispersed Ru clusters confined on boron carbon nitride (BCN) support. Compared to RuO2 , our BCN-supported catalyst shows enhanced charge transfer. It displays a low overpotential of 164 mV at a current density of 10 mA cm-2 , suggesting its excellent OER catalytic activity. This catalyst was able to operate continuously for over 12 h under acidic conditions, whereas RuO2 without any support fails in 1 h. Density functional theory (DFT) calculations confirm that the interaction between the N on BCN support and Ru clusters changes the adsorption capacity and reduces the OER energy barrier, which increases the electrocatalytic activity of Ru.

Inhibition of Fatty Acid ß-Oxidation by Fatty Acid Binding Protein 4 Induces Ferroptosis in HK2 Cells Under High Glucose Conditions.

BACKGRUOUND: Ferroptosis, which is caused by an iron-dependent accumulation of lipid hydroperoxides, is a type of cell death linked to diabetic kidney disease (DKD). Previous research has shown that fatty acid binding protein 4 (FABP4) is involved in the regulation of ferroptosis in diabetic retinopathy. The present study was constructed to explore the role of FABP4 in the regulation of ferroptosis in DKD. METHODS: We first detected the expression of FABP4 and proteins related to ferroptosis in renal biopsies of patients with DKD. Then, we used a FABP4 inhibitor and small interfering RNA to investigate the role of FABP4 in ferroptosis induced by high glucose in human renal proximal tubular epithelial (HG-HK2) cells. RESULTS: In kidney biopsies of DKD patients, the expression of FABP4 was elevated, whereas carnitine palmitoyltransferase-1A (CP-T1A), glutathione peroxidase 4, ferritin heavy chain, and ferritin light chain showed reduced expression. In HG-HK2 cells, the induction of ferroptosis was accompanied by an increase in FABP4. Inhibition of FABP4 in HG-HK2 cells changed the redox state, sup-pressing the production of reactive oxygen species, ferrous iron (Fe2+), and malondialdehyde, increasing superoxide dismutase, and reversing ferroptosis-associated mitochondrial damage. The inhibition of FABP4 also increased the expression of CPT1A, reversed lipid deposition, and restored impaired fatty acid ß-oxidation. In addition, the inhibition of CPT1A could induce ferroptosis in HK2 cells. CONCLUSION: Our results suggest that FABP4 mediates ferroptosis in HG-HK2 cells by inhibiting fatty acid ß-oxidation.

Acupuncture May Help to Prevent Chemotherapy-Induced Peripheral Neuropathy: A Randomized, Sham-Controlled, Single-Blind Study.

OBJECTIVE: This study investigated the efficacy of acupuncture in preventing chemotherapy-induced peripheral neuropathy (CIPN) in patients with colorectal cancer (CRC). METHODS: This single center, randomized, controlled, single-blind clinical trial randomly assigned patients with stage 3 CRC attending outpatient clinics in China Medical University Hospital to either verum or sham acupuncture treatment concurrently with chemotherapy. Primary outcomes were nerve conduction velocity (NCV) and touch thresholds of limb terminals. Secondary outcomes were total and subdomain scores on the Functional Assessment of Cancer Therapy-General (FACT-G), and scores on the FACT/GOG-Ntx subscale and the Brief Pain Inventory-Short Form (BPI-SF), at baseline, weeks 12, 36, and follow-up (week 48). RESULTS: Thirty-two patients met the inclusion criteria and received verum acupuncture (N = 16) or sham acupuncture (N = 16). Under the -intent-to-treat principle, 26 participants were analyzed. Significant changes from baseline for questionnaire scores and sensory NCV were observed in both study groups. Sham acupuncture was associated with significant reductions from baseline in motor NCV and sensory touch thresholds; no such changes were observed with verum acupuncture. No serious adverse events were reported. CONCLUSION: Prophylactic acupuncture may exert neuroprotective effects on mechanical or tactile touch thresholds during chemotherapy regimens in patients with CRC, with evidence of this protectiveness persisting at 6 months' follow-up. The lack of change in motor NCV values with verum acupuncture indicates neuroprotective effects. Sensory NCV values and patient-reported outcomes did not differ significantly between the study groups.

ZIP14 is involved in iron deposition and triggers ferroptosis in diabetic nephropathy.

Ferroptosis is caused by lipid peroxidation and iron accumulation and can cause cell death. Abnormally expressed iron transporters are involved in ferroptosis in a variety of diseases. ZRT/IRT-like protein 14 (ZIP14) is a transport protein that can mediate cellular uptake of iron, zinc, and manganese. Herein, we have tested the hypothesis that the divalent metal transporter ZIP14 is involved in the initiation of ferroptosis in diabetic nephropathy (DN). DN was induced in 8-week-old male rats by streptozotocin before analysis of the degree of renal tubular injury. In addition, an in vitro model of DN in human kidney proximal tubular cell line was used. We showed that ZIP14 was up-regulated and ferrous iron (Fe2+) levels increased both in vivo and in vitro. Expression of glutathione peroxidase 4 and the level of glutathione were reduced, whereas that of malondialdehyde (MDA) increased. Ferrostatin-1 (Fer-1) treatment reduced the expression of ZIP14 and the levels of Fe2+ and MDA, which is consistent with ferroptosis. Fer-1 improved kidney function in DN rats. This was characterized by urine levels of protein-to-creatinine ratio, α1-microglobulin, and N-acetyl-ß-D-glucosaminidase. Our study demonstrates a novel role for ZIP14 in diabetic kidney injury mediated by ferroptosis, and suggests a potential new therapeutic approach for the treatment of diabetic nephropathy.

Increased eEF2K Promotes Glycolysis and Aggressive Behaviors of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis.

Objective: Aggressive phenotype and abnormal glycolytic metabolism of fibroblast-like synoviocytes (FLSs) are essential to joint inflammation and damage in rheumatoid arthritis (RA). Eukaryotic elongation factor-2 kinase (eEF2K) is a negative regulator of protein synthesis and has been shown to play an important role in regulating various cellular processes and promoting glycolysis in tumor cells. However, the role of eEF2K in regulating the pathogenic FLS behaviors is unknown. Methods: A specific inhibitor of eEF2K, NH125, and siRNA were used to evaluate the role of eEF2K on RA FLSs in vitro. Collagen-induced arthritis (CIA) mice were used to evaluate the in vivo effect of eEF2K. Cell migration, invasion of RA FLSs were assessed by transwell or wound healing assays. Relative changes of cytokines were analyzed by quantitative real-time PCR, western blot and ELISA. Results: Herein, we found an increased expression of eEF2K in synovial tissues and FLSs of RA patients. eEF2K knockdown by siRNA or treatment with NH125, an inhibitor of eEF2K, significantly reduced inflammation, migration/invasion, glucose uptake and lactate productions. eEF2K knockdown suppressed TNF-α-induced activation of NF-κB and AKT pathways in RA FLSs. Lactate reversed the inhibitory effect of eEF2K knockdown on inflammation and migration of RA FLSs. Moreover, lactate was also involved in eEF2K-mediated activation of NF-κB and AKT. NH125 treatment attenuated the severity of arthritis in collagen-induced arthritis mice. Conclusion: eEF2K inhibition suppressed glycolysis and aggressive behaviors of RA FLS, which indicated that targeting eEF2K may be a new strategy for the treatment of RA.

The Association Between Acupuncture Therapies and Reduced Fracture Risk in Patients with Osteoarthritis: A Nationwide Retrospective Matched Cohort Study.

Objective: The aim of this study is to investigate the association between acupuncture therapy and the risk of fracture in patient with osteoarthritis (OA). Design: The authors performed a 1:1 propensity score-matched cohort study to analyze patient with OA between January 1, 1997 and December 31, 2010 through the Taiwanese National Health Insurance Research Database. Patients who received acupuncture therapy from the initial date of diagnosis of OA to December 31, 2010 were included in the acupuncture cohort. Patients who did not receive acupuncture during the same follow-up period were defined as the no-acupuncture cohort. A Cox regression model was used to adjust for sex, age, comorbidities, prescription, and surgical experiences. Hazard ratios (HRs) were compared between the two cohorts. Results: A total of 3416 patients were identified after 1:1 propensity score matching. The patients had similar basic characteristics. In the final analysis, 292 patients in the acupuncture cohort (30.06 per 1000 person-years) and 431 patients in the no-acupuncture cohort (56.08 per 1000 person-years) developed fractures (adjusted HRs 0.57, 95% confidence interval 0.49-0.67). A reduced cumulative incidence of fracture was found in the acupuncture cohort (log-rank test, p < 0.001). The association between acupuncture and reducing the fracture incidence was independent of sex, comorbidities, drugs use, and surgical experiences. Conclusion: Their results revealed the association between acupuncture therapies and a reduced incidence of fracture development in patients with OA. This finding provides noteworthy ideas for further research.

Flipped Classroom Approach Used in the Training of Mass Casualty Triage for Medical Undergraduate Students.

OBJECTIVE: The aim of this study was to explore the application of the flipped classroom approach in the training of Mass Casualty Triage (MCT) to medical undergraduate students. METHODS: In this study, 103 fourth-year medical students were randomly divided into a Flipped Classroom (FC) group (n = 51) and a Traditional Lecture-based Classroom (TLC) group (n = 52). A post-class quiz, simulated field triage (SFT) and feedback questionnaires were performed to assess both groups of students for their learning of the course. RESULTS: In the post-quiz, the median (IQR) scores achieved by students from the FC and TLC groups were 42(5) and 39(5.5), respectively. Significant differences were found between the two groups. In the SFT, overall triage accuracy was 67.06% for FC, and 64.23% for TLC students. Over-triage and under-triage errors occurred in 18.43% and 14.50% of the FC group, respectively. The TLC group had a similar pattern of 20.77% over-triage and 15.0% under-triage errors. No significant differences were found regarding overall triage accuracy or triage errors between the two groups. CONCLUSIONS: The FC approach could enhance course grades reflected in the post-quiz and improve students' satisfaction with the class. However, there was no significant difference of competency between the two groups demonstrated in the SFT exercise.

Inhibitory Effect of Punicalagin on Inflammatory and Angiogenic Activation of Human Umbilical Vein Endothelial Cells.

Punicalagin, a major ellagitannin isolated from pomegranate, is proved to have various pharmacological activities with an undefined therapy mechanism. The objective of this research was to demonstrate the effect of punicalagin on anti-inflammatory and angiogenic activation in human umbilical vein endothelial cells (HUVECs) and their potential mechanisms. Endothelial-leukocyte adhesion assay was applied to evaluate primary cultures of HUVECs activation following tumor necrosis factor alpha (TNF-α) treatment. The endothelial cell proliferation, migration, permeability and tube formation were assessed by EdU assay, wound migration assay, trans-endothelial electrical resistances (TEER) assay, and capillary-like tube formation assay, respectively. In addition, the expression of relevant proteins was assessed using Western blot analysis. We confirmed that punicalagin could reduce the adhesion of human monocyte cells to HUVECs in vitro and in vivo. Further, punicalagin decreased the expression of mRNA and proteins of ICAM-1 and VCAM-1 in HUVECs. Moreover, punicalagin inhibited permeability, proliferation, migration, and tube formation in VEGF-induced HUVECs, suppressed IKK-mediated activation of NF-κB signaling in TNF-α-induced endothelial cells, and inhibited vascular endothelial growth factor receptor 2 (VEGFR2) activation and downstream p-PAK1. Our findings indicated that punicalagin might have a protective effect on HUVECs activation, which suggested that punicalagin functions through an endothelial mediated mechanism for treating various disorders such as, cancer, rheumatoid arthritis, and cardiovascular disease.

Acupuncture Treatment is Associated with a Decreased Risk of Dementia in Patients with Depression: A Propensity Score-Matched Cohort Study.

BACKGROUND: Depression is one of the most disabling disorders, which causes long-term complications such as neurodegenerative disorder and cerebrovascular disease. Some patients with depression seek acupuncture treatment. We aimed to investigate the association between acupuncture treatment and the risk of dementia in patients with depression from the perspective of real-world evidence. METHODS: Patients over 18 years old and newly diagnosed with depression between 1997 and 2010 were selected from the Taiwanese National Health Insurance Research Database and followed up until the end of 2013. Propensity score was used to match equal numbers of patients 1:1 (N = 16,609 per group) into acupuncture and non-acupuncture cohorts based on characteristics including sex, age, baseline comorbidity and drug use. The outcome measurement was the comparison of dementia incidence in the two cohorts. RESULTS: Compared with the non-acupuncture cohort, patients who received acupuncture treatment had a decreased risk of dementia (adjusted hazard ratio (aHR) = 0.54; 95% confidence interval (CI) = 0.50-0.58, P < 0.001) after adjustment for age, sex, comorbidities and drug use. Compared with depression patients who did not receive acupuncture, the aHR of vascular dementia and Alzheimer's disease incidences for patients who had acupuncture therapy was 0.59 (95% CI 0.48-0.71) and 0.51 (95% CI 0.39-0.67), respectively. The cumulative incidence of dementia was significantly lower in the acupuncture cohort than in the non-acupuncture cohort (Log rank test, p < 0.001). CONCLUSION: The present study from real-world data revealed that acupuncture reduced the risk of dementia in depression patients, which supports healthcare decisions in clinical practice.

Psoralea corylifolia L. Ameliorates Collagen-Induced Arthritis by Reducing Proinflammatory Cytokines and Upregulating Myeloid-Derived Suppressor Cells.

Background: Rheumatoid arthritis is an autoimmune disease that may lead to severe complications. The fruit of Psoralea corylifolia L. (PCL) is widely used in traditional Chinese medicine as a well-known herbal treatment for orthopedic diseases. However, there is a lack of studies of its effects on rheumatoid arthritis. The purpose of the study was to investigate the effects and mechanisms of concentrated herbal granules of PCL on rheumatoid arthritis to provide some insights for future development of new drug for the treatment of rheumatoid arthritis. Methods: We used collagen-induced arthritis (CIA) DBA/1J mice as an experimental model to mimic human rheumatoid arthritis. The mice were immunized with collagen on days 0 and 21 and then orally administered 200 mg/kg/day PCL on days 22-49. Starch was used as a control. The mice were sacrificed on day 50. Clinical phenotypes, joint histopathology, and immunological profiles were measured. Results: Compared to the CIA or CIA + Starch group, the CIA + PCL group had significantly ameliorated clinical severity and decreased paw swelling. Histopathological analysis of the hind paws showed that PCL mitigated the erosion of cartilage and the proliferation of synovial tissues. There were significant differences in the levels of TNF-α, IL-6 and IL-17A, as measured by ELISA, and the percentages of CD4 + IL-17A+, CD4 + TNF-α+, CD4 + IFN-γ+ T cells. Furthermore, we also found that in mice treated with CIA + PCL, the percentage and number of bone marrow-derived suppressor cells (MDSCs; Gr1+ CD11b+) increased significantly. Conclusions: We provided evidence for the potential antiarthritic effects of PCL through the inhibition of inflammation and increase of MDSCs. These findings indicate that PCL may be a promising therapeutic herb for the treatment of rheumatoid arthritis.

Acupuncture Treatment Reduced the Risk of Coronary Heart Disease in Patients with Depression: A Propensity-Score Matched Cohort Study.

BACKGROUND: Major depressive disorder is a significant public health concern, which often leads to loss of productivity, functional decline, and various complications. The aim of this study was to investigate the effectiveness of acupuncture in the risk reduction of coronary heart disease (CHD) in patients with depression. METHODS: We enrolled patients diagnosed with depression between January 1, 1997, and December 31, 2010, through the Taiwanese National Health Insurance Research Database (NHIRD). Propensity score was used to match equal numbers (n=14,647) of acupuncture cohort and no-acupuncture cohort based on characteristics including sex, age, baseline comorbidity and medication. Patients were followed up until December 31, 2013, or withdrawn from the NHIRD. The Cox regression model was used to compare the hazard ratios (HRs) of CHD in the two cohorts. RESULTS: The basic characteristics of the two groups were similar. A lower cumulative incidence of CHD was noted in the acupuncture cohort (Log rank test, p < 0.001). Over time, 1626 patients in the acupuncture cohort (21.05 per 1000 person-years) and 2412 patients in the no-acupuncture cohort (39.84 per 1000 person-years) developed CHD (adjusted HR=0.50, 95% CI 0.47-0.53). The decreased CHD incidence was independent of age, sex, comorbidities, and medications used. The cumulative incidence of CHD was significantly lower in the acupuncture cohort than in the no-acupuncture cohort (Log rank test, p<0.001). CONCLUSION: The results provided a real-world evidence that acupuncture may have beneficial effect on CHD risk reduction in patients with depression.

Punicalagin Inhibited Inflammation and Migration of Fibroblast-Like Synoviocytes Through NF-κB Pathway in the Experimental Study of Rheumatoid Arthritis.

BACKGROUND: The aggressive phenotype of fibroblast-like synoviocytes (FLSs) is essential in the synovitis and bone destruction in rheumatoid arthritis (RA). Punicalagin is a natural polyphenol extracted in pomegranate juice, which possesses antioxidant, anti-inflammatory and anti-tumor properties suggesting it may be a potent drug for RA therapy. However, there is paucity of information on its effect in RA. OBJECTIVE: To investigate the effects of punicalagin on synovial inflammation and bone destruction in RA. METHODS: FLSs were isolated from synovial tissue of RA patients. The mRNA levels were evaluated by quantitative real-time PCR. Western blot was used for protein level measurements. The secretion of pro-inflammatory cytokines and metalloproteinases (MMPs) was detected by ELISA assays. Edu staining assays were carried out to investigate the proliferation of FLSs. Cell migration was assessed by Boyden chambers, wound scratch assays and F-actin staining in vitro. The intracellular translocation of nuclear factor kappa B (NF-κB) was investigated using immunofluorescence. The effects of punicalagin in vivo were measured by using collagen-induced arthritis (CIA) mice. RESULTS: Punicalagin treatments significantly reduced the TNF-α induced expressions of pro-inflammatory cytokines (IL-1ß, IL-6, IL-8 and IL-17A) and MMPs (MMP-1 and MMP-13) of RA FLSs. Punicalagin also suppressed the proliferation and migration of RA FLSs. Moreover, punicalagin (50mg/kg/d) alleviated arthritis severity and bone destruction, and decreased serum IL-6 and TNF-α in CIA mice. Further mechanism studies indicated that punicalagin blocked NF-κB activation via suppressing phosphorylation of IKK and IkBα, and preventing the translocation of 65. CONCLUSION: Our findings suggested that punicalagin might be one of natural therapeutic compounds for relieving RA progress via suppressing FLSs inflammation and migration through modulating NF-κB pathways.

Acupuncture decreased the risk of stroke among patients with fibromyalgia in Taiwan: A nationwide matched cohort study.

BACKGROUND: The aim of this study was to investigate the effectiveness of acupuncture in decreasing the risk of stroke in patients with fibromyalgia. METHODS: We enrolled patients who was newly diagnosed as having fibromyalgia between 1 January, 2000 and 31 December, 2010 from the Taiwanese National Health Insurance Research Database. The claim data for both the acupuncture cohort and non-acupuncture cohort were assessed from the index date to 31 December, 2013. A Cox regression model adjusted for age, sex, comorbidities, and drugs use was used to compare the hazard ratios of the two cohorts. The cumulative incidence of stroke was estimated by using the Kaplan-Meier method. RESULTS: After performing a propensity score matching with a 1:1 ratio, there were 65,487 patients in the acupuncture and non-acupuncture cohorts with similar distributions in the baseline characteristics. The cumulative incidence of stroke was significantly lower in the acupuncture cohort (log-rank test, p < 0.001). In the follow-up period, 4,216 patients in the acupuncture cohort (11.01 per 1000 person-years) and 6,849 patients in the non-acupuncture cohort (19.82 per 1000 person-years) suffered from stroke (adjusted HR 0.53, 95% CI 0.51-0.55). Acupuncture favorably affected the incidence of stroke regardless of the patient's age, sex, comorbidities, and conventional drug use. CONCLUSIONS: Our study found that acupuncture might have a beneficial effect on reducing the risk of stroke in patients with fibromyalgia in Taiwan. Additional clinical and basic science studies are warranted.

A retrospective study of the relationship between the pathologic subtype and lymph node metastasis of lung adenocarcinomas of ≤3 cm diameter.

To analyze the relationship between pathologic subtype and lymph node metastasis for lung adenocarcinomas of ≤3 cm diameter.We retrospectively studied 384 patients with operable lung adenocarcinomas of ≤3 cm diameter that had been radically resected by lobectomy or anatomic segmentectomy with systematic nodal dissection, at the Fujian Medical University Union Hospital between March 2014 and March 2016.Lymph node metastasis pN1 + pN2 (pN+) was found in 2 of 104 (1.9%) patients with tumor diameter ≤1.0 cm, 12 of 159 (7.5%) patients with tumor diameter >1.0 cm but ≤2.0 cm, and 35 of 121 (28.9%) patients with tumor size >2.0 cm but ≤3.0 cm (P < .01). Lymph node metastasis pN+ was found in 19 of 53 (35.8%) patients with visceral invasion pleural (VIP) and 30 of 331 (9.0%) patients without VIP (P < .05). It was also found in 16 of 51 (31.3%) patients with high serum CEA concentrations and 28 of 297 (9.4%) patients with normal concentrations (P < .05). In a multivariate analysis, tumor diameter, VIP, high serum CEA concentration, and pathologic subtype were significant risk factors. The prevalences of lymph node metastasis pN+ were: 0.0% (0/2), 0.0% (0/89), 3.2% (1/31), 16.2% (34/209), 7.7% (1/13), 46.7% (7/15), 100% (4/4), and 11.8% (2/17) for adenocarcinoma in situ (AIS); minimally invasive adenocarcinoma (MIA); predominantly lepidic (LEP), acinar (ACI), papillary, solid (SOL), and micropapillary (MIP) tumors; and variants of invasive adenocarcinoma, respectively (P < .05). For predominant SOL and MIP tumors, the prevalences of lymph node involvement were significantly higher than for the other subtypes.We have shown that lymph node metastasis in patients with tumor diameter ≤3 cm differs according to lung adenocarcinoma subtype. AIS and MIA were not associated with lymph node metastasis; therefore, systematic nodal dissection may be unnecessary. The prevalence of lymph node metastasis rate was low for LEP, suggesting that systemic lymph node sampling is sufficient. In contrast, for other pathologic subtypes, including SOL and MIP, systematic lymph node dissection should be performed.