Saccharina Japonica Polysaccharides Suppress High-Fat Diet-Induced Obesity and Modulate Gut Microbiota Composition and Function.

Recent studies have highlighted the potential of Saccharina japonica Polysaccharides (SJPs) in alleviating high-fat diet (HFD)-induced obesity by regulating gut microbiota, which warrants further exploration to elucidate the underlying structure-activity relationship. In this study, five polysaccharide fractions (Sj-T, Sj-T-1, Sj-T-2, Sj-T-3, and Sj-T-4) with different structure characteristics were prepared from S. japonica, and their effects on HFD-induced obesity and gut microbiota composition were investigated using C57BL/6J mice. The results revealed that oral administration of Sj-T considerably suppressed HFD-induced obesity, glucose metabolic dysfunction, and other disordered symptoms. While, Sj-T-2, which has the lowest molecular weight, was the most effective in alleviating HFD-induced obesity and had the second-best effect on improving HFD-induced impaired glucose tolerance among the five SJPs. Supplementation with SJPs significantly modulated HFD-induced gut microbiota dysbiosis both at the phylum and species levels, such as enriching Desulfobacterota and Actinobacteriota, while suppressing the abundance of Bacteroidota. Sj-T also dramatically restored the gut microbiota composition by modulating the abundance of many crucial gut bacterial taxa, including s_Bacteroides_acidifaciens, s_Lachnospiraceae _bacterium, and g_Lachnospiraceae_NK4A136_group. Besides, SJPs also dramatically altered the function of gut microbiota, including many carbohydrate-metabolism enzymes. This study highlights the potential of SJPs in preventing obesity and restoring intestinal homeostasis in obese individuals.

A case of acquired thrombotic thrombocytopenic purpura induced by acute severe hepatitis E: successfully treated by plasma exchange and rituximab.

With its low morbidity and high mortality rates, thrombotic thrombocytopenic purpura (TTP) has imposed a critical physical and economic burden on both society and individuals. Thrombocytopenia commonly occurs in severe liver failure, and a variety of hepatitis viruses are known to induce immune thrombocytopenic purpura. However, TTP is extremely rare in hepatitis E virus infection. We hereby report a case of a 53-year-old male who present with TTP caused by severe hepatitis E, and the patients achieved successful recovery after treatment. Therefore, we propose considering AMAMTS13 testing as an essential and beneficial approach for accurately diagnosing and treating patients with severe hepatitis or infection with notable platelet decline.

Incidence and risk factors of nasogastric feeding intolerance in moderately-severe to severe acute pancreatitis.

BACKGROUND: The importance of enteral nutrition (EN) in acute pancreatitis (AP) has been emphasised. Nasogastric (NG) feeding has been the preferred route for EN delivery in most AP patients intolerant to oral intake. However, gastric feeding intolerance (GFI) was frequently reported, especially in patients with more severe diseases. This study aimed to investigate the incidence and risk factors for GFI in moderately-severe to severe AP. METHODS: This is a single-centre, retrospective study. All the data were extracted from an electronic database from April 2020 to May 2021. Data were prospectively collected during hospitalisation. Patients diagnosed with moderately-severe to severe AP and admitted within seven days from the onset of abdominal pain were assessed for eligibility. Patients who showed signs of intolerance to gastric feeding and required switching to nasojejunal (NJ) feeding were deemed GFI. Multivariable logistic regression was performed to assess potential risk factors of GFI. RESULTS: A total of 93 patients were analysed, of whom 24 were deemed GFI (25.8%), and the rest tolerated NG feeding well (n = 69). In patients with GFI, the median time of switching to NJ feeding was five days (interquartile range: 4-7 days) after admission. The multivariable analysis showed that respiratory failure (odds ratio = 3.135, 95% CI: 1.111-8.848, P = 0.031) was an independent risk factor for GFI.The mean daily energy delivery in the following three days after switching to NJ feeding was significantly higher than the first three days after initiation of NG feeding in patients with GFI [920.83 (493.33-1326) vs. 465 (252.25-556.67) kcal, P < 0.001]. CONCLUSION: GFI is common in moderately-severe to severe AP patients with an incidence of 25.8%, and the presence of respiratory failure may increase the risk of GFI.

Effect of Acupuncture for Postprandial Distress Syndrome: A Randomized Clinical Trial.

BACKGROUND: Postprandial distress syndrome (PDS) is the most common subtype of functional dyspepsia. Acupuncture is commonly used to treat PDS, but its effect is uncertain because of the poor quality of prior studies. OBJECTIVE: To assess the efficacy of acupuncture versus sham acupuncture in patients with PDS. DESIGN: Multicenter, 2-group, randomized clinical trial. (ISRCTN registry number: ISRCTN12511434). SETTING: 5 tertiary hospitals in China. PARTICIPANTS: Chinese patients aged 18 to 65 years meeting Rome IV criteria for PDS. INTERVENTION: 12 sessions of acupuncture or sham acupuncture over 4 weeks. MEASUREMENTS: The 2 primary outcomes were the response rate based on overall treatment effect and the elimination rate of all 3 cardinal symptoms: postprandial fullness, upper abdominal bloating, and early satiation after 4 weeks of treatment. Participants were followed until week 16. RESULTS: Among the 278 randomly assigned participants, 228 (82%) completed outcome measurements at week 16. The estimated response rate from generalized linear mixed models at week 4 was 83.0% in the acupuncture group versus 51.6% in the sham acupuncture group (difference, 31.4 percentage points [95% CI, 20.3 to 42.5 percentage points]; P < 0.001). The estimated elimination rate of all 3 cardinal symptoms was 27.8% in the acupuncture group versus 17.3% in the sham acupuncture group (difference, 10.5 percentage points [CI, 0.08 to 20.9 percentage points]; P = 0.034). The efficacy of acupuncture was maintained during the 12-week posttreatment follow-up. There were no serious adverse events. LIMITATION: Lack of objective outcomes and daily measurement, high dropout rate, and inability to blind acupuncturists. CONCLUSION: Among patients with PDS, acupuncture resulted in increased response rate and elimination rate of all 3 cardinal symptoms compared with sham acupuncture, with sustained efficacy over 12 weeks in patients who received thrice-weekly acupuncture for 4 weeks. PRIMARY FUNDING SOURCE: Beijing Municipal Science and Technology Commission.

MicroRNA-27 attenuates pressure overload-Induced cardiac hypertrophy and dysfunction by targeting galectin-3.

Cardiac hypertrophy is an adaptive response to hemodynamic stress to compensate for cardiac dysfunction. MicroRNAs can regulate cardiac function and play a vital role in the regulation of cardiac hypertrophy. In the current study, in vivo and vitro hypertrophy models are established to explore the role of miR-27b and to elucidate the underlying mechanism in cardiac hypertrophy. Expression of miR-27b was down-regulated in mice with cardiac hypertrophy. The cardiac function of the mice with cardiac hypertrophy could be restored with the overexpression of miR-27b, this is observed in terms of decreasing LVEDd, LVESd, and increasing LVFS, LVEF. This study also predicted and confirmed that galectin-3 is a target gene of miR-27b. Depletion of galectin-3 significantly attenuated hypertrophy of hearts in both in vitro and in vivo tests. In conclusion, MiR-27b be used to exert a protective role against cardiac dysfunction and hypertrophy by decreasing the expression level of galectin-3. The methodology suggested in this study provides a novel therapeutic strategy against cardiac hypertrophy.

Galectin-3 knock down inhibits cardiac ischemia-reperfusion injury through interacting with bcl-2 and modulating cell apoptosis.

Acute myocardial infarction (AMI) is a fetal cardiovascular disease with high morbidity and mortality worldwide. In the present study, we elucidated the role of galectin-3 in preventing myocardial ischemic reperfusion injury. We found that galactin-3 was significantly up-regulated in the myocardium and cardiomyocyte subjected to ischemia/reperfusion (I/R) and hypoxia/reoxygenation (H/R) treatment, respectively. Galectin-3 knockdown significantly decreased the ischemic size of the left ventricular and the apoptosis of cardiomyocytes. Moreover, galectin-3 knockdown reversed the decrease of mitochondrial membrane potential and inhibited the inflammation response in myocardium and cultured cardiomyocyte induced by I/R and H/R, respectively. Further, this study revealed that galectin-3 interacted with bcl-2, instead of bax, in the cardiomyocyte, and regulated the phosphorylation of AKT, p70s6k, JNK, IκB and p65. Our findings demonstrated that galectin-3 could prevent myocardial I/R injury through interacting with bcl-2.

Effectiveness of acupuncture for vascular cognitive impairment no dementia: a randomized controlled trial.

OBJECTIVE:: To evaluate the effectiveness of acupuncture in patients with vascular cognitive impairment no dementia (VCIND) in comparison with citicoline, an agent for cognitive disturbances associated with chronic cerebral disorders. DESIGN:: A randomized controlled multicenter trial. SETTING:: In three hospitals in Beijing, China. SUBJECTS:: A total of 216 patients with VCIND were recruited. INTERVENTIONS:: Patients with VCIND (mean age of 65.4 years) were randomized to receive acupuncture (two sessions per week) or oral citicoline (100 mg three times daily) over three months. MAIN MEASURES:: The primary outcome was the change from baseline to three months in cognitive symptom, measured by Alzheimer's disease Assessment Scale, cognitive subscale (ADAS-cog). Secondary outcomes included changes from baseline to six months in ADAS-cog, executive function measured by the Clock Drawing Test (CDT), and functional disability measured by the Ability of Daily Living (ADL) scale at three and six months. RESULTS:: At three months, the acupuncture group had a greater decrease in mean ADAS-cog score (-2.33 ± 0.31) than the citicoline group (-1.38 ± 0.34) with a mean difference of -0.95 (95% CI, -1.84 to -0.07, P = 0.035). The mean change from baseline to six months in ADAS-cog also significantly favored acupuncture treatments (acupuncture change -2.61 vs citicoline -1.25, difference: -1.36 points; 95% CI, -2.20 to -0.51; P = 0.002). There was no difference between the two groups on CDT and ADL scores at either time point. CONCLUSION:: Compared with citicoline, acupuncture has comparable and even superior efficacy with improved cognitive and daily living performance as a complementary and alternative medicine treatment for VCIND.

Risk Prediction for Portal Vein Thrombosis in Acute Pancreatitis Using Radial Basis Function.

BACKGROUND: Acute pancreatitis (AP) can induce portosplenomesenteric vein thrombosis (PVT), which may generate higher morbidity and mortality. However current diagnostic modalities for PVT are still controversial. In recent decades, artificial neural networks have been increasingly applied in medical research. The aim of this study is to predict the risk of AP-induced PVT by radial basis function (RBF) artificial neural networks (ANNs) model. METHODS: A retrospective or consecutive study of 426 individuals with AP at our unit between January 1, 2011 and July 31, 2016 was conducted. All individuals were subjected to RBF ANNs. Variables included age, gender, red blood cell specific volume (Hct), prothrombin time (PT), fasting blood glucose, D-Dimer, concentration of serum calcium ([Ca2+]), triglyceride, serum amylase (AMY), acute physiology and chronic health evaluation II score, and Ranson score. All outcomes were derived after subjecting the variables to a statistical analysis. RESULTS: In the RBF ANNs model, D-dimer, AMY, Hct, and PT were the important factors among all 11 independent variables for PVT. The normalized importance of them was 100%, 96.3%, 71.9%, and 68.2%, respectively. The predict sensitivity, specificity, and accuracy by RBF ANNs model for PVT were 76.2%, 92.0%, and 88.1%, respectively. There were significant differences between the RBF ANNs and logistic regression models in these parameters (95% CI: 110.9% [-0.4 to 15.8%]; 8.4% [-3.3 to 19.2%]; and 12.8% [1.6-20.7%], respectively). In addition, the area under receiver operating characteristic curves value for identifying thrombosis when using the RBF ANNs model was 0.892 ± 0.091 (95% CI: 0.805-0.951), demonstrating better overall performance than the logistic regression model (0.762 ± 0.073; 95% CI: 0.662-0.839). CONCLUSIONS: The RBF ANNs model was a valuable tool in predicting the risk of PVT following AP. AMY, D-dimer, PT, and Hct were important prediction factors of approval for AP-induced PVT.

Effectiveness and feasibility of acupuncture for knee osteoarthritis: a pilot randomized controlled trial.

OBJECTIVE:: To evaluate the effectiveness of acupuncture for pain relief and function improvement in patients with knee osteoarthritis and to determine the feasibility of an eight-week acupuncture intervention. DESIGN:: Pilot randomized controlled trial. SETTING:: Three teaching hospitals in China. SUBJECTS:: Patients with knee osteoarthritis (Kellgren grade II or III). INTERVENTIONS:: Patients were randomly assigned to an eight-week (three sessions per week) intervention of either traditional Chinese acupuncture or sham acupuncture. MAIN MEASURES:: The primary outcome was response rate-the proportion of patients achieving score ⩾36% decrease in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function at week 8 compared with baseline. Secondary outcomes included pain, function and quality of life. RESULTS:: Of 42 patients randomized, 36 (85.7%) completed the study. There was no significant difference in response rate between the traditional Chinese acupuncture and control groups: 61.9% (13 of 21) versus 42.9% (9 of 21) achieved score ⩾36% decrease in WOMAC pain and function at week 8 ( P = 0.217). The sum of WOMAC pain and function scores at week 8 was 11.6 (9.1) in the traditional Chinese acupuncture group compared with 16.3 (10.9) in the control group ( P = 0.183). There was no significant difference between groups. Three adverse events were recorded and were classified as mild. CONCLUSION:: It showed that three sessions per week acupuncture intervention of knee osteoarthritis was feasible and safe. No difference was observed between groups due to small sample size. Larger (sample size ⩾ 296) randomized controlled trials of this intervention appear justified.

MicroRNA-1296 inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by targeting SRPK1-mediated PI3K/AKT pathway.

BACKGROUND: Increasing evidences demonstrate that miRNAs contribute to development and progression of hepatocellular carcinoma (HCC). Underexpression of miR-1296 is recently reported to promote growth and metastasis of human cancers. However, the expression and role of miR-1296 in HCC remain unknown. METHODS: The levels of miR-1296 in HCC tissues and cells were detected by qRT-PCR. Immunoblotting and immunofluorescence were used for detection of epithelial-to-mesenchymal transition (EMT) progression in HCC cells. Transwell assays were performed to determine migration and invasion of HCC cells. A lung metastasis mouse model was used to evaluated metastasis of HCC in vivo. The putative targets of miR-1296 were disclosed by public databases and a dual-luciferase reporter assay. RESULTS: We found that the expression of miR-1296 was reduced in HCC tissues and cell lines, and it was associated with metastasis and recurrence of HCC. Notably, miR-1296 overexpression inhibited migration, invasion and EMT progress of HCCLM3 cells, while miR-1296 loss facilitated these biological behaviors of Hep3B cells in vitro and in vivo. In addition, miR-1296 inversely regulated SRPK1 abundance by directly binding to its 3'-UTR, which subsequently resulted in suppression of p-AKT. Either SRPK1 re-expression or PI3K/AKT pathway activation, at least partially, abolished the effects of miR-1296 on migration, invasion and EMT progress of HCC cells. Furthermore, miR-1296 and SRPK1 expression were markedly correlated with adverse clinical features and poor prognosis of HCC patients. We showed that hypoxia was responsible for the underexpression of miR-1296 in HCC. And the promoting effects of hypoxia on metastasis and EMT of HCC cells were reversed by miR-1296. CONCLUSIONS: Underexpression of miR-1296 potentially serves as a prognostic biomarker in HCC. Hypoxia-induced miR-1296 loss promotes metastasis and EMT of HCC cells probably by targeting SRPK1/AKT pathway.

HSP90 promotes cell glycolysis, proliferation and inhibits apoptosis by regulating PKM2 abundance via Thr-328 phosphorylation in hepatocellular carcinoma.

BACKGROUND: Heat shock protein 90 (HSP90) functions as a well-known onco-protein to regulate protein conformation, stability and degradation. Pyruvate kinase M2 (PKM2), a critical regulator of the metabolism, growth and metastasis of cancer cells, has been confirmed to be overexpressed in various human cancer including hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying the oncogenic functions of HSP90 and PKM2 overexpression in HCC remain unknown. METHODS: The expression of HSP90 and PKM2 in HCC specimens and cells were detected by immunoblotting and immunostaining. The interaction between HSP90 and PKM2 was confirmed by tandem affinity purification, co-immunoprecipitation and Glutathione S transferase (GST)-pulldown assay. RESULTS: In this study, we found that HSP90 could bind to PKM2 and subsequently increased PKM2 abundance in HCC cells. Immunohistochemistry (IHC) staining showed that HSP90 level was positively correlated with PKM2 level in HCC tissues. Mechanistically, HSP90 was found to increase the phosphorylation of PKM2 at Thr-328. Protein kinase glycogen synthase kinase-3ß (GSK-3ß) formed a protein complex with HSP90 and PKM2, and directly mediated Thr-328 phosphorylation of PKM2 induced by HSP90. Thr-328 phosphorylation was critical for maintaining PKM2 stability and its biological functions in regulating glycolysis, mitochondria respiration, proliferation and apoptosis. Functionally, we found that HSP90 promoted the glycolysis and proliferation and inhibited apoptosis of HCC cells in a PKM2 dependent manner. In vivo experiments disclosed that PKM2 was required for the promoting effects of HSP90 on the growth of HCC cells in mice. Furthermore, we demonstrated that positive expression of HSP90 and PKM2 was correlated with poor clinicopathological features including high alpha fetoprotein (AFP) level, large tumor size, portal vein tumor thrombus (PVTT) and advanced tumor-node-metastasis (TNM) stage. Furthermore, we demonstrated that positive expression of HSP90 and PKM2, and a combination of these proteins could strongly predict the poor prognosis of HCC patients. CONCLUSIONS: We suggest that HSP90 potentiates the glycolysis and proliferation, reduces the apoptosis and thus enhances the growth of HCC cells through PKM2.

Endocrine and exocrine pancreatic insufficiency after acute pancreatitis: long-term follow-up study.

BACKGROUND: Patients could develop endocrine and exocrine pancreatic insufficiency after acute pancreatitis (AP), but the morbidity, risk factors and outcome remain unclear. The aim of the present study was to evaluate the incidence of endocrine and exocrine pancreatic insufficiency after AP and the risk factors of endocrine pancreatic insufficiency through a long-term follow-up investigation. METHODS: Follow-up assessment of the endocrine and exocrine function was conducted for the discharged patients with AP episodes. Oral Glucose Tolerance Test (OGTT) and faecal elastase-1(FE-1) test were used as primary parameters. Fasting blood-glucose (FBG), fasting insulin (FINS), glycosylated hemoglobin HBA1c, 2-h postprandial blood glucose (2hPG), Homa beta cell function index (HOMA-ß), homeostasis model assessment of insulin resistance (HOMA-IR) and FE-1 were collected. Abdominal contrast-enhanced computed tomography (CECT) was performed to investigate the pancreatic morphology and the other related data during hospitalization was also collected. RESULTS: One hundred thirteen patients were included in this study and 34 of whom (30.1%) developed diabetes mellitus (DM), 33 (29.2%) suffered impaired glucose tolerance (IGT). Moreover, 33 patients (29.2%) developed mild to moderate exocrine pancreatic insufficiency with 100µg/g50%, WON and insulin resistance were the independent risk factors of new onset diabetes after AP.

[Effects of L-carnitine and bisoprolol on endoplasmic reticulum stress-mediated myocardial injury after cardiopulmonary resuscitation in rats].

OBJECTIVE: To explore the effects of L-carnitine and bisoprolol on endoplasmic reticulum stress-mediated myocardial injury after cardiopulmonary resuscitation in rats. METHODS: A total of 75 Sprague-Dawley rats were randomly divided into 5 groups of sham operation (sham); cardiopulmonary resuscitation (CR), L-carnitine (L), bisoprolol treatment (B) and L-carnitine and bisoprolol treatment (LB). Myocardial pathological changes were detected by hematoxylin and eosin, myocardial apoptosis by terminal deoxynucleotidyl transferase mediated dUTP nick and the expressions of key factors in endoplasmic reticulum (ER) by Western blot. RESULTS: Compared with sham group, apoptosis and pathological lesions significantly increased in other groups (P < 0.05). And the levels of GRP78, CHOP and Caspase-12 were significantly higher (P < 0.05). The expression of ER factor protein and the degrees of myocardial injury in LB and B groups decreased compared with CR group. And LB group was the most obvious. CONCLUSIONS: Combined use of levocarnitine and bisoprolol exerts protective effects on cardiopulmonary resuscitation in rats. And the mechanism may be related to an inhibition of ER stress.

Electroacupuncture versus exercise in patients with knee osteoarthritis: Study protocol for a randomized controlled trial.

PURPOSE: Knee osteoarthritis (KOA) is a common disorder among middle and older individuals. Electroacupuncture and exercise are present as two popular physical therapies for the management of KOA, and both were demonstrated to produce considerable results. However, the clinical decision-making process between these therapeutic interventions remains challenging due to the limited evidence of distinctions in their respective effects. This study aims to evaluate the clinical effect and cost effectiveness of electroacupuncture versus exercise in patients with KOA. STUDY DESIGN AND METHODS: This is a randomized controlled trial in which 196 symptomatic KOA patients will be randomly assigned 1:1 either to the electroacupuncture group (n = 98) and the exercise group (n = 98). Patients in the electroacupuncture group will receive acupuncture with electric stimulation 3 times a week for 8 weeks, whereas patients in the exercise group will receive neuromuscular training twice a week for 8 weeks. Education concerning KOA management will be provided in both therapies. Co-primary outcomes include changes in numerical rating scale (NRS) and Knee injury and Osteoarthritis Outcome Score (KOOS) Activities of Daily Living (ADL) subscale from baseline at week 8. Secondary outcomes include KOOS Pain subscale, KOOS knee-related Quality of Life (QOL) subscale, Short Form 6 Dimensions (SF-6D), five-level EuroQol five-dimensional questionnaire (EQ-5D-5L), Credibility/ Expectancy Questionnaire, Patient's global assessment (PGA), 30-second Chair Stand Test (30s-CST), 40m (4*10m) Fast Paced Walk Test (40m FPWT), and Daily Physical Activity level (DPA). DISCUSSION: The results of this study will provide evidence regarding differences between these 2 physical therapies in multiple aspects and will provide specific guidance for the development of treatments based on the needs of individual patients. TRIAL REGISTRATION: ChiCTR2300070376.

Electroacupuncture Ameliorates Knee Osteoarthritis By Rebalancing T Cell Homeostasis as Revealed By Immune Repertoire (IR) Sequencing.

BACKGROUND: In this study, we used immune repertoire (IR) sequencing technology to profile the diversity of peripheral blood T cell receptors and used transcriptomics to profile the gene expression of peripheral blood neutrophil mRNA in patients with mild-moderate knee osteoarthritis (KOA) before and after electroacupuncture (EA) treatment. METHODS: An 8-week intervention with EA was performed on 3 subjects with KOA. IR sequencing of complementarity determining region 3 (CDR3) was performed using RNA extracted from peripheral blood T cells of KOA subjects prior to and at the end of the intervention, as well as healthy volunteers (controls) who matched the subjects in sex and age. Neutrophils were extracted from the plasma of healthy individuals, pretreatment patients, and posttreatment patients for further transcriptome sequencing. RESULTS: The D50, diversity index (DI), and Shannon entropy values of circulatory T-cells were significantly lower in pretreatment KOA patients compared to healthy controls. Posttreatment KOA samples displayed significant decreases in serum proinflammatory factors, IL-8 and IL-18 (P < 0.01), as well as a substantial reduction in serum matrix MMP-3 and MMP-13 (P < 0.01, P < 0.05). Transcriptome analysis revealed that the expression of CXCL2, IRF8, and PEAR1 (P < 0.05) was significantly higher in patients before the treatment than in the healthy population and was significantly down-regulated after the treatment. In contrast, the expression of SMPD3 (P < 0.05) showed the opposite trend. CONCLUSION: EA may alleviate KOA by rebalancing T-cell homeostasis and improving systemic inflammation. At the same time, EA treatment can significantly enhance TCR diversity, reduce levels of proinflammatory factors, and increase levels of anti-inflammatory factors, thereby achieving therapeutic effects.

Effect of 4 weeks vs 8 weeks of acupuncture for knee osteoarthritis in China: protocol for a randomised controlled trial.

INTRODUCTION: Knee osteoarthritis represents the prevalent and incapacitating disease. Acupuncture, a widely used clinical treatment for knee osteoarthritis, has been shown to ameliorate pain and enhance joint function in affected individuals. However, there is a lack of evidence comparing different courses of acupuncture for knee osteoarthritis. In this trial, we will assess the effect of 4 weeks vs 8 weeks of acupuncture in patients with knee osteoarthritis. METHODS AND ANALYSIS: The protocol is a pragmatic, parallel, two-arm randomised controlled trial, with the data analyst and assessor being blinded. 148 eligible patients with knee osteoarthritis will be randomly allocated in a 1:1 ratio to receive 4-week or 8-week acupuncture. Electroacupuncture will be administered three times per week for 4 or 8 weeks, respectively. Patients with knee osteoarthritis in both groups will be followed up to 26 weeks. The primary outcome is the response rate at week 26, and secondary outcomes include knee joint pain, knee joint function, knee joint stiffness, quality of life, patient global assessment, the Osteoarthritis Research Society International response rate and rescue medicine. A cost-effectiveness analysis will be carried out over 26 weeks. ETHICS AND DISSEMINATION: The protocol has been approved by the Medical Ethical Committee of Beijing University of Chinese Medicine (2023BZYL0506). The study findings will be disseminated through presentation in a medical journal. Additionally, we plan to present them at selected conferences and scientific meetings. TRIAL REGISTRATION NUMBER: Chinese Clinical Trials Registry (ChiCTR2300073383; https://www.chictr.org.cn/showproj.html?proj=199310).

Acupuncture for response and complete pain relief time of acute renal colic: Secondary analysis of a randomized controlled trial.

Background: The integration of acupuncture with intramuscular injection of diclofenac sodium can expedite the onset of analgesia in treating acute renal colic caused by urolithiasis. However, it remains unclear whether acupuncture can accelerate pain relief constantly until complete remission. This study aimed to explore the extent to which acupuncture can expedite the onset time of response or complete pain relief in treating acute renal colic, and the predictive value of patient characteristics for treatment efficacy. Methods: This secondary analysis utilized data from a prior randomized controlled trial. Eighty patients with acute renal colic were randomly assigned 1:1 to the acupuncture group or the sham acupuncture group. After intramuscular injection of diclofenac sodium, acupuncture or sham acupuncture was delivered to patients. The outcomes included time to response (at least a 50 % reduction in pain) and complete pain relief. Between-group comparison under the 2 events was estimated by Kaplan-Meier methodology. Subgroup analysis was performed utilizing the Cox proportional hazards model. Results: The median response time and complete pain relief time in the acupuncture group were lower than those in the sham acupuncture group (5 vs 30 min, Log Rank P < 0.001; 20 min vs not observed, Log Rank P < 0.001, respectively). Hazard Ratios (HRs) for response across all subgroups favored the acupuncture group. All HRs for complete pain relief favored acupuncture, expect large stone and moderate pain at baseline. No interaction was found in either event. Conclusion: Acupuncture can accelerate the response time and complete pain relief time for patients with acute renal colic, with the efficacy universally. Trial registration: This study has been registered at Chinese Clinical Trial Registry: ChiCTR1900025202.

Acupuncture Modulation of Chronic Neuropathic Pain and Its Association With Brain Functional Properties.

Chronic neuropathic pain has been one of the prominent causes of disability, and acupuncture has shown promise in treatment. The present study aimed to characterize acupuncture modulation of chronic neuropathic pain and explore the related functional brain changes. Sixty chronic sciatica patients were divided into acupuncture- or sham acupuncture groups and received 10 sessions of treatment during 4 weeks. The visual analog scale for leg pain, oswestry disability index (ODI), and resting-state functional magnetic resonance images were assessed at baseline and after treatment. Then, fractional amplitudes of low-frequency fluctuations (fALFF) and support vector regression analyses were performed. Compared with sham acupuncture, acupuncture significantly improved symptoms, including visual analog scale for leg pain and ODI. In addition, acupuncture exhibited increased fALFF of the right superior parietal lobule (SPL) and right postcentral gyrus. Furthermore, the actual 4-week ODI values were positively correlated with the support vector regression-predicted values based on the right SPL fALFF and baseline clinical measurements. These results indicate that the spontaneous neural activity of the right SPL and right postcentral gyrus may be involved in the modulation of acupuncture in chronic neuropathic pain. In addition, the spontaneous neural activity of the right SPL might be used as the predictor of response to acupuncture therapy. PERSPECTIVE: This clinical neuroimaging study elucidated the neural basis of acupuncture in chronic sciatica. Neurological indicators and clinical measurements could be used as potential predictors of acupuncture response. This study combines neuroimaging and artificial intelligence techniques to highlight the potential of acupuncture for the treatment of chronic neuropathic pain. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR2100044585, http://www.chictr.org.cn.

Sodium tanshinone IIA sulfonate protects rat myocardium against ischemia-reperfusion injury via activation of PI3K/Akt/FOXO3A/Bim pathway.

AIM: To investigate the mechanisms underlying the protective effects of sodium tanshinone IIA sulfonate (STS) in an ischemia-reperfusion (I/R)-induced rat myocardial injury model. METHODS: Male SD rats were iv injected with STS, STS+LY294002 or saline (NS) for 15 d. Then the hearts were subjected to 30 min of global ischemia followed by 2 h of reperfusion. Cardiac function, infarction size and area at risk were assessed. Cell apoptosis was evaluated with TUNEL staining, DNA laddering and measuring caspase-3 activity. In addition, isolated cardiomyocytes of neonatal rats were pretreated with the above drugs, then exposed to H2O2 (200 mol/L) for 1 h. Cell apoptosis was detected using flow cytometric assay. The levels of p-Akt, p-FOXO3A and Bim were examined with immunoblotting. RESULTS: Compared to NS group, administration of STS (20 mg/kg) significantly reduced myocardial infarct size (40.28%±5.36% in STS group vs 59.52%±7.28% in NS group), and improved the myocardial function as demonstrated by the increased values of dp/dtmax, LVDP and coronary flow at different reperfusion time stages. Furthermore, STS significantly decreased the rate of apoptotic cells (15.11%±3.71% in STS group vs 38.21%±7.83% in NS group), and reduced caspase-3 activity to nearly a quarter of that in NS group. Moreover, STS significantly increased the phosphorylation of Akt and its downstream target FOXO3A, and decreased the expression of pro-apoptotic gene Bim. Co-treatment with the PI3K inhibitor LY294002 (40 mg/kg) partially countered the protective effects induced by STS treatment. In isolated cardiomyocytes, STS exerted similar protective effects as shown in the ex vivo I/R model. CONCLUSION: STS pretreatment reduces infarct size and improves cardiac function in an I/R-induced rat myocardial injury model via activation of Akt/FOXO3A/Bim-mediated signal pathway.