A common trajectory of gut microbiome development during the first month in healthy neonates with limited inter-individual environmental variations.

The early development of the gut microbiome is governed by multiple factors and has significantly long-term effects on later-in-life health. To minimize inter-individual variations in the environment, we determined developmental trajectories of the gut microbiome in 28 healthy neonates during their stay at a postpartum center. Stool samples were collected at three time points: the first-pass meconium within 24 h of life, and at 7 and 28 days of age. Illumina sequencing of the V3-V4 region of 16S rRNA was used to investigate microbiota profiles. We found that there was a distinct microbiota structure at each time point, with a significant shift during the first week. Proteobacteria was most abundant in the first-pass meconium; Firmicutes and Actinobacteria increased with age and were substituted as the major components. Except for a short-term influence of different delivery modes on the microbiota composition, early microbiome development was not remarkably affected by gravidity, maternal intrapartum antibiotic treatment, premature rupture of membranes, or postnatal phototherapy. Hence, our data showed a similar developmental trajectory of the gut microbiome during the first month in healthy neonates when limited in environmental variations. Environmental factors external to the host were crucial in the early microbiome development.

Modified Buyang Huanwu Decoction alleviates diabetic liver injury via inhibiting oxidative stress in db/db mice.

OBJECTIVES: In diabetes, chronic hyperglycemia increases the overactivation of oxidative phosphorylation of mitochondria in the liver, resulting in oxidative stress (OS) damage. The Nrf2 signaling pathway plays a key role in preventing hepatic oxidative injury and inflammation. This study aims to investigate the therapeutic effect and mechanism of Modified Buyang Huanwu Decoction (mBYHWD) on diabetic liver injury (DLI) by regulating oxidative stress mediated by Nrf2 signaling pathway. METHODS: The experiment was divided into three groups: a control group (db/m mice, Con), a diabetes model group (db/db mice, Mod), and a traditional Chinese medicine group (db/m mice, mBYHWD). Post-treatment, serum from each group was analyzed to assess changes of blood glucose, blood lipid, and liver function. These results were combined with data mining to explore the possible pathogenesis of DLI. Liver tissues were collected to observe the pathological morphology and detect related proteins. RESULTS: The results demonstrated that mBYHWD significantly reduced blood lipids and improved liver function following diabetic liver injury. The histopathological results demonstrated that mBYHWD could significantly ameliorate damage of diabetic hepatocytes. Protein analysis revealed that mBYHWD treatment significantly increased the expression of antioxidant proteins in diabetic liver tissue and inhibited inflammation. CONCLUSIONS: The therapeutic mechanism of mBYHWD on DLI may involve activating the Nrf2 signaling pathway to improve oxidative stress, inhibit inflammation, and reduce liver tissue fibrosis.

The clinical application of traditional Chinese medicine NRICM101 in hospitalized patients with COVID-19.

BACKGROUND: The aim of this study was to assess the efficacy and safety of NRICM101 in hospitalized patients with COVID-19. RESEARCH DESIGN AND METHODS: We conducted a retrospective study from 20 April 2021 to 8 July 2021, and evaluated the safety and outcomes (mortality, hospital stay, mechanical ventilation, oxygen support, diarrhea, serum potassium) in COVID-19 patients. Propensity score matching at a 1:2 ratio was performed to reduce confounding factors. RESULTS: A total of 201 patients were analyzed. The experimental group (n = 67) received NRICM101 and standard care, while the control group (n = 134) received standard care alone. No significant differences were observed in mortality (10.4% vs. 14.2%), intubation (13.8% vs. 11%), time to intubation (10 vs. 11 days), mechanical ventilation days (0 vs. 9 days), or oxygen support duration (6 vs. 5 days). However, the experimental group had a shorter length of hospitalization (odds ratio = 0.12, p = 0.043) and fewer mechanical ventilation days (odds ratio = 0.068, p = 0.008) in initially severe cases, along with an increased diarrhea risk (p = 0.035). CONCLUSION: NRICM101 did not reduce in-hospital mortality. However, it shortened the length of hospitalization and reduced mechanical ventilation days in initially severe cases. Further investigation is needed.

The effects of laser acupuncture dosage at PC6 (Neiguan) on brain reactivity: a pilot resting-state fMRI study.

Previous studies indicated that laser acupuncture (LA) may effectively treat various medical conditions. However, brain responses associated with LA intervention have not been fully investigated. This study is focused on the effect of LA with different energy density (ED) in brain using resting-state functional magnetic resonance imaging (fMRI). We hypothesized that different ED would elicit various brain responses. We enrolled healthy adults participants and selected bilateral PC6 (Neiguan) as the intervention points. LA was applied, respectively, with ED of 0, 7.96, or 23.87 J/cm2. Two 500-s resting-state fMRI scans were acquired before and after intervention, respectively. The functional connectivity (FC) was calculated between autonomic nerve system-regulation associated brainstem structures and other brain regions. Compared to other dosages, the FC between rostral ventrolateral medulla and orbitofrontal cortex has more enhanced; the FC between caudal ventrolateral medulla, nucleus of the solitary tract/nucleus ambiguus, and dorsal motor nucleus of the vagus and somatosensory area has more weakened when ED was 23.87 J/cm2. Different dosages of LA have demonstrated varied regions of FC changes between regions of interest and other brain areas, which indicated that variations in EDs might influence the clinical efficacy and subsequent impacts through distinct neural pathways within the brain.

DNA Methylation Biomarkers as Prediction Tools for Therapeutic Response and Prognosis in Intermediate-Stage Hepatocellular Carcinoma.

INTRODUCTION: Alfa-fetoprotein (AFP), as the main serum tumor marker of hepatocellular carcinoma (HCC), is limited in terms of specificity and ability to predict outcomes. This study investigated the clinical utility of DNA methylation biomarkers to predict therapeutic responses and prognosis in intermediate-stage HCC. METHODS: This study enrolled 72 patients with intermediate-stage HCC who underwent locoregional therapy (LRT) between 2020 and 2021. The immediate therapeutic response and disease status during a two-year follow-up were recorded. Analysis was performed on 10 selected DNA methylation biomarkers via pyrosequencing analysis of plasma collected before and after LRT. RESULTS: Analysis was performed on 53 patients with complete responses and 19 patients with disease progression after LRT. The mean follow-up duration was 2.4 ± 0.6 years. A methylation prediction model for tumor response (MMTR) and a methylation prediction model for early progression (MMEP) were constructed. The area under the curve (AUC) for sensitivity and specificity of MMTR was 0.79 for complete response and 0.759 for overall survival. The corresponding AUCs for sensitivity and specificity of AFP and protein induced by vitamin K absence-II (PIVKA-II) were 0.717 and 0.708, respectively. Note that the MMTR index was the only significant predictor in multivariate analysis. The AUC for sensitivity and specificity of the MMEP in predicting early progression was 0.79. The corresponding AUCs for sensitivity and specificity of AFP and PIVKA-II were 0.758 and 0.714, respectively. Multivariate analysis revealed that platelet count, beyond up-to-7 criteria, and the MMEP index were strongly correlated with early tumor progression. Combining the indexes and serum markers further improved the predictive accuracy (AUC = 0.922). Multivariate analysis revealed the MMEP index was the only independent risk factor for overall survival. DISCUSSION/CONCLUSIONS: This study indicates that these methylation markers could potentially outperform current serum markers in terms of accuracy and reliability in assessing treatment response and predicting outcomes. Combining methylation markers and serum markers further improved predictive accuracy, indicating that a multi-marker approach may be more effective in clinical practice. These findings suggest that DNA methylation biomarkers may be a useful tool for managing intermediate-stage HCC patients and guiding personalized treatment, particularly for those who are at high risk for close surveillance or adjuvant treatment after LRT.

Ligustrazine improves the compensative effect of Akt survival signaling to protect liver Kupffer cells in trauma-hemorrhagic shock rats.

Trauma-hemorrhagic shock (THS) is a medical emergency that is encountered by physicians in the emergency department. Chuan Xiong is a traditional Chinese medicine and ligustrazine is a natural compound from it. Ligustrazine improves coronary blood flow and reduces cardiac ischemia in animals through Ca2+ and ATP-dependent vascular relaxation. It also decreases the platelets' bioactivity and reduces reactive oxygen species formation. We hypothesized that ligustrazine could protect liver by decreasing the inflammation response, protein production, and apoptosis in THS rats. Ligustrazine at doses of 100 and 1000 µg/mL was administrated in Kupffer cells isolated from THS rats. The protein expressions were detected via western blot. The THS showed increased inflammation response proteins, mitochondria-dependent apoptosis proteins, and had a compensation effect on the Akt pathway. After ligustrazine treatment, the hemorrhagic shock Kupffer cells decreased inflammatory response and mitochondria-dependent apoptosis and promoted a more compensative effect of the Akt pathway. It suggests ligustrazine reduces inflammation response and mitochondria-dependent apoptosis induced by THS in liver Kupffer cells and promotes more survival effects by elevating the Akt pathway. These findings demonstrate the beneficial effects of ligustrazine against THS-induced hepatic injury, and ligustrazine could be a potential medication to treat the liver injury caused by THS.

[Exploring the location of acupoint Dubi (ST35)].

Acupoint Dubi(ST35), one of the commonly used acupuncture points in clinical practice, has long been equated as the acupoint Waixiyan(EX-LE5) in the academic community. By referring to the location of ST35 elaborated in the relevant literature in the ancient and modern times, we analyze the evolution of its position and expound its clinical significance of the correct positioning in the present paper. We think that under posture of knee flexion, the position of ST35 should be between the lower edge of the patella and the upper tip of the tibia, at the midpoint of the patella ligament.

Analgesic Efficacy of Acupuncture on Chronic Pelvic Pain: A Systemic Review and Meta-Analysis Study.

Chronic pelvic pain (CPP) is the pain occurred in the pelvic region longer than six months. The monotherapy of medicine may not adequate for the pain management of CPP and multidisciplinary approaches have been more recommended. The aim of this study is to evaluate the pain management efficacy of acupuncture compared with a control group on CPP. The articles of randomized controlled trial on CPP in PubMed and Embase databases were screened between January 2011 and September 2022 without language restriction to evaluate the treatment efficacy of acupuncture. The visual analogue scale/numerical rating scale (VAS/NRS) and total pain scores of National Institutes of Health-chronic prostatitis symptom index (NIH-CPSI) were served as outcome variables. Post-intervention mean scores were extracted and pooled for meta-analysis. Seventeen studies including 1455 patients were selected for meta-analysis. Both total pain scores of NIH-CPSI and VAS/NAS data revealed significant lower pain level in the acupuncture group than in the control group. Moreover, monotherapy with acupuncture revealed a significantly lower pain level than in the control group in both total pain scores of NIH-CPSI and VAS/NRS. These results indicated that acupuncture may have beneficial effects on pain management for CPP, even when administrated as a monotherapy.

The efficacy and safety of cupping as complementary and alternative therapy for metabolic syndrome: A systematic review and meta-analysis.

INTRODUCTION: This systematic review and meta-analysis aimed to assess the efficacy and safety of cupping therapy in patients with metabolic syndrome (MetS). METHODS: This systematic review focused on patients with MetS and included randomized controlled trials (RCTs) that compared the effects of cupping therapy with control groups. A total of 12 electronic databases were searched from inception until February 03, 2023. The main outcome after the meta-analysis was waist circumference; the others included anthropometric variables, blood pressure, lipid profile, fasting blood glucose level, and high-sensitivity C-reactive protein level. The incidence of adverse events and the follow-up courses were also evaluated. Risk of bias (ROB) was evaluated using ROB 2.0 from the Cochrane Handbook. RESULTS: This systematic review included five studies involving 489 patients. Some risks of bias were also identified. The meta-analysis revealed a statistically significance in waist circumference (MD = -6.07, 95% CI: -8.44 to -3.71, P < .001, I2 = 61%, τ2 = 3.4), body weight (MD = -2.46, 95% CI: -4.25 to -0.68, P = .007, I2 = 0%, τ2 = 0) and body mass index (MD = -1.26, 95% CI: -2.11 to -0.40, P = .004, I2 = 0%, τ2 = 0) between the cupping therapy and control groups. However, there were no significant results in total fat percentage and blood pressure values. Regarding biochemical markers, cupping significantly lowered the concentration of low-density lipoprotein cholesterol (MD = -3.98, 95% CI: -6.99 to -0.96, P = .010, I2 = 0%, τ2 = 0) but had no significant effect on total cholesterol, triglyceride, high-density lipoprotein cholesterol, fasting blood glucose, and high-sensitivity C-reactive protein. 3 RCTs reported no adverse events. CONCLUSIONS: Despite some ROB and low to substantial heterogeneity of the included studies, cupping therapy can be considered a safe and effective complementary intervention for reducing waist circumference, body weight, body mass index, and low-density lipoprotein cholesterol in patients with MetS. In the future, well-designed, high-quality, rigorous methodology, and long-term RCTs in this population are required to assess the efficacy and safety of cupping therapy.

A randomized trial on the effect of transcutaneous electrical nerve stimulator on glycemic control in patients with type 2 diabetes.

Transcutaneous electrical nerve stimulator (TENS) has been demonstrated to be beneficial in glycemic control in animal models, but its application in humans has not been well studied. We randomly assigned 160 patients with type 2 diabetes on oral antidiabetic drugs 1:1 to the TENS study device (n = 81) and placebo (n = 79). 147 (92%) randomized participants (mean [SD] age 59 [10] years, 92 men [58%], mean [SD] baseline HbA1c level 8.1% [0.6%]) completed the trial. At week 20, HbA1c decreased from 8.1% to 7.9% in the TENS group (- 0.2% [95% CI - 0.4% to - 0.1%]) and from 8.1% to 7.8% in the placebo group (- 0.3% [95% CI - 0.5% to - 0.2%]) (P = 0.821). Glycemic variability, measured as mean amplitude of glycemic excursion (MAGE) at week 20 were significantly different in the TENS group vs. the placebo group (66 mg/dL [95% CI 58, 73] vs. 79 mg/dL [95% CI 72, 87]) (P = 0.009). Our study provides the clinical evidence for the first time in humans that TENS does not demonstrate a statistically significant HbA1c reduction. However, it is a safe complementary therapy to improve MAGE in patients with type 2 diabetes.

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.

A comprehensive tool for tumor precision medicine with pharmaco-omics data analysis.

Background: Cancer precision medicine is an effective strategy to fight cancers by bridging genomics and drug discovery to provide specific treatment for patients with different genetic characteristics. Although some public databases and modelling frameworks have been developed through studies on drug response, most of them only considered the ramifications of the drug on the cell line and the effects on the patient still require a huge amount of work to integrate data from various databases and calculations, especially concerning precision treatment. Furthermore, not only efficacy but also the adverse effects of drugs on patients should be taken into account during cancer treatment. However, the adverse effects as essential indicators of drug safety assessment are always neglected. Method: A holistic estimation explores various drugs' efficacy levels by calculating their potency both in reversing and enhancing cancer-associated gene expression change. And a method for bridging the gap between cell culture and living tissue estimates the effectiveness of a drug on individual patients through the mappings of various cell lines to each person according to their genetic mutation similarities. Result: We predicted the efficacy of FDA-recommended drugs, taking into account both efficacy and toxicity, and obtained consistent results. We also provided an intuitive and easy-to-use web server called DBPOM (http://www.dbpom.net/, a comprehensive database of pharmaco-omics for cancer precision medicine), which not only integrates the above methods but also provides calculation results on more than 10,000 small molecule compounds and drugs. As a one-stop web server, clinicians and drug researchers can also analyze the overall effect of a drug or a drug combination on cancer patients as well as the biological functions that they target. DBPOM is now public, free to use with no login requirement, and contains all the data and code. Conclusion: Both the positive and negative effects of drugs during precision treatment are essential for practical application of drugs. DBPOM based on the two effects will become a vital resource and analysis platform for drug development, drug mechanism studies and the discovery of new therapies.

Retinal protective effect of curcumin metabolite hexahydrocurcumin against blue light-induced RPE damage.

BACKGROUND: Age-related macular degeneration (AMD) is a disease of retinal pigment epithelium (RPE) cells. We have previously demonstrated that blue light can damage RPE cells and their underlying mechanisms. We found that hexahydrocurcumin (HHC), a metabolite of curcumin, had better retinal protection than curcumin. However, the involved mechanisms remain unclear. METHODS: By exposing ARPE-19 human RPE cells and mouse primary RPE cells to blue light, the intracellular mechanisms of HHC in cells were investigated, including the proliferation of RPE cells and the effects of HHC on activating intracellular protective mechanisms and related factors. Next-generation sequencing (NGS) RNA sequencing revealed the underlying mechanisms involved in the induction and regulation of HHC treatment following blue light exposure. RESULTS: HHC promoted autophagy by enhancing autophagic flux, reduced oxidative stress and endoplasmic reticulum (ER) stress, and effectively reversed blue light-induced cell death. RNA sequencing-based bioinformatics approaches comprehensively analyze HHC-mediated cellular processes. CONCLUSION: Our findings elucidate the mechanisms of HHC against blue light damage in RPE cells and are beneficial for the development of natural metabolite-based preventive drugs or functional foods.

The Dosage Effect of Laser Acupuncture at PC6 (Neiguan) on Heart Rate Variability: A Pilot Study.

Laser acupuncture (LA) has been more applicated in the clinical practice with good responses, but the dosage and parameter settings are still inconsistent with the arguments. This study is focused on the effect of LA on heart rate variability (HRV) with different energy density (ED). Based on the Arndt-Schulz law, we hypothesized that the effective range should fall within 0.01 to 10 J/cm2 of ED, and settings above 10 J/cm2 would perform opposite or inhibitory results. We recruited healthy adults in both sexes as subjects and choose bilateral PC6 (Neiguan) as the intervention points to observe the HRV indexes changes by an external wrist autonomic nerve system (ANS) watch on the left forearm. The data from the ANS watch, including heart rate, blood pressure, and ANS activity indexes, such as low frequency (LF), high frequency (HF), LF%, HF%, LF/HF ratio, and so on, were analyzed by the one-way ANOVA method to test the possible effect. In this study, every subject received all three different EDs of LA in a randomized order. After analyzing the data of 20 subjects, the index of HF% was upward and LF/HF ratio was downward when the ED was 7.96 J/cm2. Otherwise, the strongest ED 23.87 J/cm2 performed the opposite reaction. Appropriately, LA intervention could affect the ANS activities, with the tendency to increase the ratio of parasympathetic and decrease the ratio of sympathetic nerve system activities with statistically significant results, and different ED interventions are consistent with Arndt-Schulz law with opposite performance below and above 10 J/cm2.

Rutin prevents seizures in kainic acid-treated rats: evidence of glutamate levels, inflammation and neuronal loss modulation.

Rutin, a naturally derived flavonoid molecule with known neuroprotective properties, has been demonstrated to have anticonvulsive potential, but the mechanism of this effect is still unclear. The current study aimed to investigate the probable antiseizure mechanisms of rutin in rats using the kainic acid (KA) seizure model. Rutin (50 and 100 mg kg-1) and carbamazepine (100 mg kg-1) were administered daily by oral gavage for 7 days before KA (15 mg kg-1) intraperitoneal (i.p.) injection. Seizure behavior, neuronal cell death, glutamate concentration, excitatory amino acid transporters (EAATs), glutamine synthetase (GS), glutaminase, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits GluA1 and GluA2, N-methyl-D-aspartate (NMDA) receptor subunits GluN2A and GluN2B, activated astrocytes, and inflammatory and anti-inflammatory molecules in the hippocampus were evaluated. Supplementation with rutin attenuated seizure severity in KA-treated rats and reversed KA-induced neuronal loss and glutamate elevation in the hippocampus. Decreased glutaminase and GluN2B, and increased EAATs, GS, GluA1, GluA2 and GluN2A were observed with rutin administration. Rutin pretreatment also suppressed activated astrocytes, downregulated the protein levels of inflammatory molecules [interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high mobility group Box 1 (HMGB1), interleukin-1 receptor 1 (IL-1R1), and Toll-like receptor-4 (TLR-4)] and upregulated anti-inflammatory molecule interleukin-10 (IL-10) protein expression. Taken together, the results indicate that the preventive treatment of rats with rutin attenuated KA-induced seizures and neuronal loss by decreasing glutamatergic hyperactivity and suppressing the IL-1R1/TLR4-related neuroinflammatory cascade.

Randomized, Placebo-Controlled Phase 2b Study to Evaluate the Safety and Efficacy of Recombinant Human Lecithin Cholesterol Acyltransferase in Acute ST-Segment-Elevation Myocardial Infarction: Results of REAL-TIMI 63B.

BACKGROUND: High-density lipoprotein plays a key role in reverse cholesterol transport. In addition, high-density lipoprotein particles may be cardioprotective and reduce infarct size in the setting of myocardial injury. Lecithin-cholesterol acyltransferase is a rate-limiting enzyme in reverse cholesterol transport. MEDI6012 is a recombinant human lecithin-cholesterol acyltransferase that increases high-density lipoprotein cholesterol. Administration of lecithin-cholesterol acyltransferase has the potential to reduce infarct size and regress coronary plaque in acute ST-segment-elevation myocardial infarction. METHODS: REAL-TIMI 63B (A Randomized, Placebo­controlled Phase 2b Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction) was a phase 2B multinational, placebo-controlled, randomized trial. Patients with ST-segment-elevation myocardial infarction within 6 hours of symptom onset and planned for percutaneous intervention were randomly assigned 2:1 to MEDI6012 (2- or 6-dose regimen) or placebo and followed for 12 weeks. The primary outcome was infarct size as a percentage of left ventricular mass by cardiac MRI at 10 to 12 weeks, with the primary analysis in patients with TIMI Flow Grade 0 to 1 before percutaneous intervention who received at least 2 doses of MEDI6012. The secondary outcome was change in noncalcified plaque volume on coronary computed tomographic angiography from baseline to 10 to 12 weeks with the primary analysis in patients who received all 6 doses of MEDI6012. RESULTS: A total of 593 patients were randomly assigned. Patients were a median of 62 years old, 77.9% male, and 95.8% statin naive. Median time from symptom onset to randomization was 146 (interquartile range [IQR], 103-221) minutes and from hospitalization to randomization was 12.7 (IQR, 6.6-24.0) minutes, and the first dose of drug was administered a median of 8 (IQR, 3-13) minutes before percutaneous intervention. The index myocardial infarction was anterior in 69.6% and TIMI Flow Grade 0 to 1 in 65.1% of patients. At 12 weeks, infarct size did not differ between treatment groups (MEDI6012: 9.71%, IQR 4.79-16.38; placebo: 10.48%, [IQR, 4.92-16.61], 1-sided P=0.79. There was also no difference in noncalcified plaque volume (geometric mean ratio, 0.96 [95% CI, NA-1.10], 1-sided P=0.30). There was no significant difference in treatment emergent serious adverse events. CONCLUSIONS: Administration of MEDI6012 in patients with acute ST-segment-elevation myocardial infarction did not result in a significant reduction in infarct size or noncalcified plaque volume at 12 weeks. MEDI6012 was well tolerated with no excess in overall serious adverse events. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03578809.

Serious bacterial infections in young children with fever without source after discharge from emergency department: A National Health Insurance database cohort study.

BACKGROUND: Well-appearing febrile young children discharged from the emergency department (ED) after medical assessment are still at risk for serious bacterial infections (SBI). The incidence of SBI and the effectiveness of laboratory tests in the pneumococcal conjugate vaccine era remain unknown. METHODS: We conducted a study using Taiwan's National Health Insurance claims data from 2004 to 2014. Children aged 2-24 months discharged from the ED with a diagnosis compatible with fever without source (FWS) were enrolled. RESULTS: The study identified 431,884 children from the ED with FWS. 13.53% of the children had revisits, 8.62% needed hospitalization and 1.57% developed SBI. Younger children had a higher SBI rate, but a lower revisit rate. The revisit rate was 12.22% for children aged 2-6 months, 13.61% for children aged 7-12 months and 13.77% for children aged 13-24 months (p < 0.0001). The SBI rate was 4.44% for children aged 2-6 months, 1.85% for children aged 2-6 months and 0.96% for children aged 13-24 months (p < 0.0001). Children with hemogram tests, compared to those without, had a higher revisit rate (16.30% vs. 13.15%, p < 0.0001), and a higher SBI rate in the children aged 13-24 months (1.30% vs. 0.92%, p < 0.0001); furthermore, children with urinalysis had a significantly higher revisit rate (14.42% vs. 13.24%, p < 0.0001) and higher SBI rate (2.10% vs. 1.40%, p < 0.0001). CONCLUSION: Children with FWS aged 2-24 months who were discharged from ED after blood test and urinalysis were still at risk for SBI, especially those aged 2-6 months.

The Clinical Observation and Mechanism of Acupuncture on Cancer-Related Fatigue of Breast Cancer Based on "Gut-Brain Axis": Study Protocol for a Randomized Controlled Trial.

Background. Cancer-related fatigue (CRF) is a painful, persistent feeling of physical and cognitive subjective fatigue related to cancer or cancer remedy. The occurrence of CRF may be related to the hypothalamic-pituitary-adrenaline (HPA) axis, inflammatory mediator theory, and gut microbiota. Moreover, acupuncture could play a vital part in the therapy of CRF. The study will evaluate whether acupuncture can improve fatigue symptoms of CRF patients after breast cancer chemotherapy by regulating the gut-brain axis. Methods/design. Seventy patients with CRF will be enrolled in this study, with 35 patients randomly assigned to each group. Blood and feces will be collected at the beginning and end of treatment. Piper fatigue scale, KPS score scale, and quality-of-life scale will be used to observe the changes of fatigue symptoms and life quality of CRF patients and to evaluate the effect of acupuncture on CRF. Then, the method of ELISA will be used to explore the regulatory effect of acupuncture on the HPA axis and inflammatory cytokines. Moreover, based on 16SrDNA, the changes of gut microbiota structure and flora of CRF patients will be observed. Ultimately, the correlation analysis of gut microbiota can be related to inflammatory cytokines, HPA axis, and clinical efficacy evaluation. Discussion. This study will identify the effect and the mechanism of acupuncture therapy in CRF. And it will offer an alternative treatment modality for the treatment of CRF after chemotherapy for breast cancer. Furthermore, it will also provide the clinical and theoretical bases for the extensive application of acupuncture therapy in tumor rehabilitation. Trial Status. Protocol version number and date: V2.0, 6 May 2021. The trial is registered with the Chinese Clinical Trial Registry on 20 June 2021 (trial identifier: ChiCTR2100047510).

Effect of Acupuncture on the Cognitive Control Network of Patients with Knee Osteoarthritis: Study Protocol for a Randomized Controlled Trial.

Purpose: Abnormal central nervous system function is the key central pathological factor leading to chronic pain in patients with knee osteoarthritis (KOA). Acupuncture can effectively relieve the pain of KOA patients. However, the central nervous mechanism of acupuncture treating KOA is not fully understood. This trial will use functional magnetic resonance imaging (fMRI) analysis techniques to investigate the potential central nervous mechanism of acupuncture treatment of KOA. Materials and Methods: A total of 108 patients will be randomized (in a 1:1:1 ratio) into three groups, this trial will include 4-week treatment, patients in groups A and B will receive 20 acupuncture and sham acupuncture sessions, respectively, patients in group C will not receive any intervention, and all patients will receive fMRI scans before and after the intervention. The Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) will be the primary clinical outcome. Then, we will explore the functional changes of the cognitive control network (CCN) in the brains of KOA patients through whole brain functional connectivity (FC) analysis and seed-based functional connectivity (sFC) analysis. Pearson correlation coefficient will be used to analyze the relationship between the improved value of the clinical correlation scale and the change of fMRI data. Discussion: This trial will analyze the efficacy of verum acupuncture, sham acupuncture and the waiting-list for KOA and explore the activity of the CCN in three groups of patients by fMRI, so as to reveal the central nervous mechanisms of acupuncture in the treatment of KOA. Study Registration: This study is approved by the Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine (No: 2019HL-133-01) and registered in the Chinese Clinical Trial Registry, ChiCTR2000038554.

Hot Air-Assisted Radio Frequency (HARF) Drying on Wild Bitter Gourd Extract.

Wild bitter gourd (Momordica charantia L. var. abbreviata S.) is a kind of Chinese herbal medicine and is also a vegetable and fruit that people eat daily. Wild bitter gourd has many bioactive components, such as saponin, polysaccharide, and protein, and the extract is used to adjust blood sugar in patients with diabetes. The objective of this study was to investigate simultaneous hot air-assisted radio frequency (HARF) drying and pasteurization for bitter gourd extract, and then to evaluate its effects on blood sugar of type II diabetic mice. The results showed that the solid-liquid ratio of the wild bitter gourd powder to water was 1:10 and it was extracted using focused ultrasonic extraction (FUE) for only 10 min with 70 °C water. Then, 1 kg of concentrated bitter gourd extract was mixed with soybean fiber powder at a ratio of 2:1.1. It was dried by HARF, and the temperature of the sample could reach above 80 °C in only 12 min to simultaneously reduce moisture content (wet basis) from 58% to 15% and achieve a pasteurization effect to significantly reduce the total bacterial and mold counts. Type II diabetic mice induced by nicotinamide and streptozocin (STZ) for two weeks and then were fed four-week feeds containing 5% RF-dried wild gourd extract did not raise fasting blood glucose. Therefore, the dried powder of wild bitter gourd extracts by HARF drying had a hypoglycemic effect.