Rate Of Disappearance Research Articles

Tolerability of the Intravenously Administered Tolvaptan Prodrug, OPC-61815, in Patients With Congestive Heart Failure Who Have Difficulty With, or Are Incapable of, Oral Intake (TRITON-HF) - A Phase III, Multicenter, Open-Label Trial.

OPC-61815, a prodrug of tolvaptan, is an injectable aquaretic drug. This study evaluated the tolerability of OPC-61815 in patients with congestive heart failure (CHF) who had difficulty with, or were incapable of, oral intake in a multicenter, uncontrolled, open-label Phase III study. Forty-five patients were enrolled at 30 Japanese sites. OPC-61815 infusion was administered once daily; the 8 mg initial dose could be increased to 16 mg if the dose escalation criteria were met. Patients were treated for up to 5 days. Thirty-eight patients maintained the 8-mg dose and 7 had a dose increase to 16 mg; 41 completed the trial (34 completed early). One patient had mild hypernatremia. No significant safety concerns were observed with OPC-61815 administration at a starting dose of 8 mg and with dose escalation in accordance with the protocol-specified criteria. Treatment resulted in weight decrease (-3.01 kg); improvement or disappearance rates for other CHF symptoms (including edema, dyspnea, orthopnea, pulmonary congestion, and rales) indicated that treatment was effective. Urine excretion was increased 0-1 h after OPC-61815 administration and reached a maximum level at 1-2 h. The tolerability of once daily (up to 5 days) intravenous OPC-61815 (8 mg or 16 mg) was confirmed in patients with CHF who had difficulty with, or were incapable of, oral intake.

Efficacy of Endoscopic Intervention plus Growth Inhibitor and Patient Self-Management in the Treatment of Esophagogastric Variceal Bleeding in Cirrhosis.

Objective To assess the efficacy of endoscopic intervention plus growth inhibitor and patient self-management in the treatment of esophagogastric variceal bleeding. Methods Between January 2019 and December 2021, 60 patients with esophagogastric variceal bleeding treated in our hospital were assessed for eligibility and randomly recruited. They were concurrently and randomly assigned at a ratio of 1 : 1 to receive either endoscopic intervention plus growth inhibitor (control group) or endoscopic intervention plus growth inhibitor and patient self-management (observation group). The endpoint is clinical efficacy. Results All eligible patients showed a similar time of hemostasis, success rate of hemostasis, rebleeding rate, and disappearance rate of varicose veins (P > 0.05). Endoscopic intervention plus growth inhibitor and patient self-management were associated with a lower incidence of complication (6.67%, including 1 (3.34%) case of ulcer and 1 (3.34%) case of fever) than endoscopic intervention plus growth inhibitor (26.67%, including 3 (10.00%) cases of ulcer, 2 (6.67%) cases of retrosternal pain, and 3 (10.00%) cases of fever) (P < 0.05). Patients in the observation group had significantly higher life satisfaction scores (25.17 ± 4.28 and 23.68 ± 5.17) than those in the control group (22.13 ± 2.24 and 18.12 ± 3.28) (P < 0.05). A decrease in life satisfaction scores was observed at 6 months after treatment, and the patients given patient self-management showed a higher satisfaction (P < 0.05). Conclusion Endoscopic intervention plus growth inhibitor and patient self-management yielded remarkable clinical efficacy in the treatment of esophagogastric variceal bleeding as it reduces the incidence of complication and enhances the life satisfaction of patients, and so it is worthy of clinical promotion.

Prospective multicenter study of the efficacy and safety of cold forceps polypectomy for ≤ 6-mm non-ampullary duodenal low-grade adenomas.

Background and study aims Because the endoscopic treatment for non-ampullary duodenal adenoma (NADA) has a non-negligible risk of adverse events (AEs), a safe and easy treatment for NADA is desirable. This was a multicenter prospective trial evaluating the efficacy and safety of cold forceps polypectomy (CFP) for diminutive NADAs. Patients and methods This study was prospectively conducted at six general hospitals and one university hospital. The inclusion criteria were histologic and endoscopic diagnosis of low-grade NADA measuring ≤ 6 mm. A second endoscopy was scheduled for 1 month after CFP. After confirmation of the success of CFP, 6-month and 12-month surveillance endoscopies were scheduled. The primary endpoint was the endoscopic and histologic disease disappearance rates at the 12-month endoscopy. Results Thirty-nine lesions from 38 patients were prospectively included. Median tumor size at enrollment was 5 mm (range 3–6 mm). There were four cases of remnant lesions at the second endoscopy, and the lesion disappearance rate of single CFP was 89.7 % (35 /39; 95 % confidence interval (CI), 76.9 %–97.9 %). In three cases, complete removal of the lesion was achieved with a single re-CFP, but one case required four repeat CFPs. The lesion disappearance rate at 12-month endoscopy was 97.4 % (38 /39; 95 %CI, 86.8 %–99.5 %). During the follow-up period, no AEs related to CFP were observed. Conclusions CFP for NADA ≤ 6 mm was safe and effective in this study. This common endoscopic method to remove lesions may be an option for treatment of diminutive NADAs.

1377-P: Pramlintide Lowers Postprandial Glucagon Concentrations by Inhibiting Glucagon Secretion without Altering Clearance in Type 1 Diabetes: A [13C15N]-Glucagon Study

To determine the underlying mechanism of pramlintide effects on postprandial (PP) glucagon concentrations, we studied thirteen C-peptide negative T1D subjects (Age 35±yrs, BMI 27.6±2.2 kg/m2, fasting plasma glucose 9.4±4 mM, HbA1c 7.1±1%) on two occasions in random order, with and without 30 μg of sc pramlintide at the onset of a mixed meal (75 gm carb, 15% fat and 35% protein; 8 kcal/kg) . Subjects administered insulin bolus at meal onset. 13C15N glucagon tracer was infused intravenously to estimate PP glucagon turnover. Arterialized venous samples were drawn periodically for measurements of glucose (YSI) , 13C15N-glucagon (LC-MS/MS) and glucagon (Mercodia) concentrations. Systemic glucagon turnover was calculated using non-steady state Steele's equation after determining glucagon volume of distribution. Integrated PP glucagon concentrations were lower (p&amp;lt;0.01) in pramlintide (Pram) than without pramlintide (No Pram) . Integrated rates of glucagon appearance and glucagon disappearance were lower (p&amp;lt;0.01) in Pram vs. No Pram. When adjusted for plasma glucagon concentrations, glucagon clearance was not different (p=0.7) between Pram vs. No Pram. These data demonstrate that pramlintide lowers postprandial glucagon concentrations by lowering glucagon secretion without altering clearance in subjects with T1D. Disclosure F.Ruchi: None. D.Romeres: None. M.Schiavon: None. S.Renuse: None. A.Pandey: None. C.Dalla man: Research Support; Becton, Dickinson and Company, Sanofi-Aventis Deutschland GmbH. C.Cobelli: None. R.Basu: Consultant; Sparrow Pharmaceuticals Inc, Research Support; Abbott Diabetes, AstraZeneca. A.Basu: Speaker's Bureau; Zealand Pharma A/S. Funding National Institute of Health (DK 085516, DK 029953)

Digestibility Kinetics of Polyhydroxyalkanoate and Poly(butylene succinate-co-adipate) after In Vitro Fermentation in Rumen Fluid.

Using polyhydroxyalkanoate (PHA) materials for ruminal boluses could allow for longer sustained release of drugs and hormones that would reduce administration time and unneeded animal discomfort caused by continuous administration. The objective of this study was to determine ruminal degradability and kinetics of biodegradable polymers and blends. A proprietary PHA-based polymer, poly(butylene succinate-co-adipate) (PBSA), PBSA:PHA melt blends, and forage controls were incubated in rumen fluid for up to 240 h. Mass loss was measured after each incubation time, and digestion kinetic parameters were estimated. Thermogravimetric, differential scanning calorimetry, and intrinsic viscosity analyses were conducted on incubated samples. Generally, across treatments, mass loss was significant by 96 h with a minimum increase of 0.25% compared to 0 h but did not change thereafter. Degradation kinetics demonstrated that polymer treatments were still in the exponential degradation phase at 240 h with a maximum disappearance rate of 0.0031 %/h. Melting temperature increased, onset thermal degradation temperature decreased, and intrinsic viscosity decreased with incubation time, indicating structural changes to the polymers. Based on these preliminary findings, the first stage of degradation occurs within 24 h and PHA degrades slowly. However, further ruminal degradation studies of biodegradable polymers are warranted to elucidate maximum degradation and its characteristics.

Efficacy and safety of Chinese herbal medicine Qirui Weishu capsule in treating chronic non-atrophic gastritis: A multicentre, double-blind, randomized controlled clinical trial

Ethnopharmacological relevanceQiruiWeishu capsule is an herbal preparation from a herbal formula prescribed by an experienced doctor at Guang'anmen Hospital of China Academy of Chinese Medical Sciences. It has been used clinically for more than 30 years. Abdominal pain, distension, and nausea are common symptoms of chronic non-atrophic gastritis with erosion dampness and heat stasis syndrome, and this herbal medicine has been used to treat them. Aim of the studyTo verify the clinical efficacy and safety of QiruiWeishu capsule in the treatment of chronic non-atrophic gastritis with damp-heat stasis syndrome. Materials and methodsThis study was a multicenter randomized double-blind clinical trial with positive herbal drug SanjiuWeitai capsule as control and superiority test of main efficacy. A total of 477 subjects with chronic non-atrophic gastritis with erosion diagnosed by gastroscopy and pathological biopsy were randomly divided into QiruiWeishu capsule and SanjiuWeitai groups respectively in a ratio of 3:1. During the trial, subjects were required to complete medication for 28 days. The primary outcome was the disappearance rate of epigastric pain from baseline to 4weeks. At baseline, treatment at 1, 2, and 4 weeks, and follow-up at 8 and 16 weeks, the epigastric pain and traditional Chinese medicine (TCM) symptom scores were evaluated; gastroscopy, histopathology, and the helicobacter pylori test were evaluated at baseline and after 4 weeks of treatment. The safety assessment included blood routine, liver and kidney function, coagulation of laboratory tests, and electrocardiogram (ECG). ResultsBoth groups of subjects had a high level of medication adherence (defined as treatment completion for over 80%) (346/357, 96.9% in Qirui Weishu group vs 118/120, 98.3% in Sanjiu Weitai group; p > 0.05). The QiruiWeishu capsule was significantly better than SanjiuWeitai capsule in disappearance rate of epigastric pain (64.2%, 229/357vs 46.7%, 56/120; p < 0.001)，especially subgroupsubjects with moderate epigastric pain (65.0%, 89/137 vs 30.4%, 14/46; p < 0.001), grade1 erythema (67.7%, 149/220 vs 51.9%, 42/81; p = 0.011) and grade 2 erythema (57.6%, 70/121 vs37.1%, 13/35; p = 0.050) of gastroscopy, grade 2 erosion (66.7%, 118/177 vs43.9%, 25/57; p = 0.002) of gastroscopy and Helicobacter pylori negative (65.4%, 155/237 vs 42.7%, 35/82; p < 0.001) at baseline. For the scores of TCM symptoms in QiruiWeishu group were significantly lower than those in SanjiuWeitai group after 28 days of treatment (p = 0.002). The number and incidence of adverse events related to the trial drug were 14/355 (3.9%) in QiruiWeishu group, 6/118 (5.1%) in SanjiuWeitai group (p > 0.05). No serious adverse reactions occurred in the two groups. According to laboratory tests and ECG, there was no discernible effect on heart, liver, kidney, or blood coagulation function. ConclusionQirui Weishu capsule appears to be more effective in terms of symptoms than the SanjiuWeitai capsule, and its use is both safe and effective for the treatment of chronic non-atrophic gastritis. A further randomized, double-blind, placebo-control trial is warranted to verify its benefit.

Spineless cactus-based diets associated with various nitrogen sources in sheep diets

This study evaluated the effects of various nitrogen (N) sources augmenting spineless cactus-based diets on intake, digestibility, rumen kinetics and N balance in sheep. Eight rumen-fistulated sheep with an average initial bodyweight of 62 ± 6.83 kg were allotted to one of two 4 x 4 Latin squares. The diets consisted of spineless cactus (Nopalea cochenillifera), Tifton hay, corn grain, vegetable oil and a mineral mixture augmented with either soybean meal (SBM), cottonseed meal (CSM), whole cottonseed (WCS) or urea (U) to provide additional nitrogen. Dry matter (DM), crude protein (CP), and neutral detergent fibre (NDF) intakes were similar (P &gt;0.05) for sheep fed the diets with SBM, CSM, and WCS. The digestibility coefficients of DM and CP were similar (P &gt;0.05) for SM, CM, and U diets. The rate of DM disappearance from the rumen did not differ (P &gt;0.05) between treatments. However, the rumen ammonia, pH and N balance was higher (P &lt;0.05) for sheep fed the WCS and U diets. The N absorbed and N retained did not differ (P &gt;0.05) between the diets. Soybean meal and CSM are similar in their effects and can be used for sheep in diets based on spineless cactus. Whole cottonseed and U are interesting sources of N but should be used with caution owing to their effects on digestibility and nutrient intake in sheep.

The effectiveness and safety of Chaiqin Qingning Capsule in upper respiratory tract infections with fever: A prospective, double-blinded, randomized, multicenter controlled trial

Background and aimPresently, over-the-counter drugs that can treat upper respiratory tract infections (URTI) are rarely effective and safe. Chaiqin Qingning Capsule (CQQNC), a Chinese patent medicine, which has been verified by long-term clinical practice is recommended by Chinese experts for the treatment of URTI with fever. This study conducted a prospective, double-blinded, randomized, multicenter controlled trial to evaluate the effectiveness and safety of CQQNC in the treatment of URTI. MethodsThe study was conducted at 4 clinical centers in China. Eligible subjects were recruited and randomized 1:1 to the CQQNC group and Qingkailing Capsule (QKLC) group. Both groups were administered orally three times a day for three consecutive days. Primary outcomes were the antipyretic onset time and the temperature recovery time. Secondary outcomes included the symptom disappearance rate, symptom score, and drug safety assessment. ResultsA total of 269 subjects were analyzed (134 subjects in the CQQNC group, 135 subjects in the QKLC group). The antipyretic onset time and the temperature recovery time were significantly shortened in the CQQNC group (median: 5 h vs. 10 h, p < 0.0001, median: 19 h vs. 27 h, p < 0.0001). CQQNC was more effective than the QKLC in improving the symptoms of pharyngodynia and rhinobyon (85.07% vs. 71.11%, p = 0.008; 76.99% vs. 64.41%, p = 0.043), and in improving the overall symptom scores (−15.10 ± 3.23 vs. −13.35 ± 3.58, p < 0.0001). During the trial, no serious adverse events were reported in the two groups. ConclusionCQQNC is effective and safe in the treatment of URTI with fever, and worthy of clinical application. (http://www.chictr.org.cn, ChiCTR-IPR-16009049).

Dynamic Changes of Cytokine Profiles and Virological Markers Associated With HBsAg Loss During Peginterferon Alpha-2a Treatment in HBeAg-Positive Chronic Hepatitis B Patients.

ObjectiveTo explore dynamic changes of cytokines and virological markers associated with hepatitis B surface antigen (HBsAg) loss during peginterferon alpha-2a (PEG-IFN α-2a) treatment in hepatitis B e antigen (HBeAg) positive chronic hepatitis B (CHB) patients.MethodsIt was a single-center prospective cohort study. HBeAg-positive CHB patients were prospectively and consecutively enrolled. Cytokines were detected at baseline, week 12 and 24 of PEG-IFN treatment. HBsAg disappearance rate was the primary evaluation index at 48 weeks of PEG-IFN treatment.ResultsAmong 100 patients who completed the 48-week PEG-IFN α-2a treatment, 38 patients achieved serum HBeAg disappearance, 25 patients achieved HBeAg seroconversion, 9 patients achieved functional cure, 37 patients had HBsAg decline of ≥1 log IU/ml, and 8 patients produced hepatitis B surface antibody (HBsAb). Albumin (ALB), fms-like tyrosine kinase 3 ligand (FLT3-L) and interferon-alpha2 (IFN-α2) in the clinical cure group were significantly lower than those in the non-clinical-cure group at baseline. After 12 weeks of treatment, HBsAg in the clinical cure group was significantly lower than that in the non-clinical-cure group (median 1.14 vs. 3.45 log10IU/ml, Z=-4.355, P < 0.001). The decrease of HBsAg and hepatitis B virus desoxyribose nucleic acid (HBV DNA) in the clinical cure group was significantly higher than that in non-clinical-cure group (median: HBsAg 1.96 vs. 0.33 log10IU/ml, Z=-4.703, P< 0.001; HBV DNA 4.49 vs.3.13 log10IU/ml, Z=-3.053, P=0.002). The increase of IFN-α2 in the cure group was significantly higher than that in the non-clinical-cure group (497.89 vs. 344.74, Z=-2.126, P=0.034). After 24 weeks of treatment, HBsAg, HBeAg, Flt3-L, and IL-10 in the clinical cure group were significantly lower than those in the non-clinical-cure group (median: HBsAg 0.70 vs. 3.15 log10IU/ml, Z=-4.535, P< 0.001; HBeAg 1.48 vs. 13.72 S/CO, Z = 2.512, P = 0.012; Flt3-l 0.00 vs 2.24 pg/ml, Z = 3.137, P=0.002; IL-10 0.70 vs. 2.71 pg/ml, Z=-4.067, P < 0.001). HBsAg decreased significantly in the clinical cure group compared with non-clinical-cure group (median 3.27 vs. 0.45, Z=-4.463, P < 0.001).ConclusionDynamic changes of cytokines and virology markers during early PEG IFN α-2a treatment were associated with HBsAg loss in HBeAg-positive CHB patients.

MO967: Lymphocele After Renal Transplantation: Management, Risk Factors and Impact on Transplant Survival

Abstract BACKGROUND AND AIMS Lymphocele after renal transplantation remains a common complication, despite all the technical precautions taken, in particular the ligation of lymphatic vessels. Its incidence varies according to the series, depending on the diagnostic methodology, and whether or not it is systematically screened. This study aims to investigate the risk factors for lymphocele and its impact on transplant survival. METHOD We performed a retrospective longitudinal descriptive study including all patients who had a kidney transplant in a Urology department from 1986 to 2017. Clinical presentation and management of lymphocele were studied. Then, the characteristics of patients who presented a lymphocele were compared with those of the rest of the population including characteristics related to the recipient, the donor, the transplant and the procedure to identify risk factors. The impact of lymphocele on patient and transplant survival was then studied. RESULTS A total of 720 patients were included with a mean age of 32.7 years. The transplant was from a living donor in 79% and a brain-dead donor in 21%. Lymphocele occurred in 51 patients (7.1%). The lymphocele was asymptomatic in 80%, and clinical manifestations were related to the compression of the transplant or its important size, requiring active treatment, most often percutaneous (13.7%). The lymphocele did not require treatment in 42 cases (82.4%) with disappearance in 90.5%. Revision surgery for a lymphocele was necessary in two cases. The risk factors for lymphocele were a cadaveric donor (P = 0.003) and an advanced age of the recipient (P &amp;lt; 0.001). No predictive factors related to the transplant (vascular anatomy), or procedure (location and type of anastomoses, ischemia time) were identified. Transplant survival was 77.9% at 5 years, with a median survival of 15.9 years. The occurrence of a lymphocele did not influence the survival of the transplant (P = 0.25) (Figure 1). CONCLUSION Our study showed that lymphocele is usually asymptomatic, not requiring a specific treatment in most cases with a high rate of spontaneous disappearance with no impact on transplant survival. Risk factors were a cadaveric donor which may reflect the absence of careful ligation of the transplant's lymphatic vessels in the context of urgent, sometimes multi-organ, cadaveric procurement and advanced recipient age.

Altered Activation of Inflammatory Signaling with Diet‐induced Insulin Resistance in the Dystrophic Diaphragm

Duchenne muscular dystrophy (DMD) affects 1 in 3500 to 5000 boys born worldwide. It is caused by the absence of functional dystrophin, a sarcolemmal protein. Dystrophin deficiency causes progressive muscle degeneration, leading to numerous cellular dysfunctions, ultimately resulting in death due to respiratory or cardiac failure. Although insulin resistance (IR) is a frequently reported comorbidity in boys with DMD, how IR impacts DMD is less studied. Additionally, the compounded effects of IR and dystropathology on cellular pathways, including inflammatory signaling, have not been previously considered. We hypothesized that a high‐fat, high sucrose diet (HF/HSD) would induce IR and cause activation of inflammatory signaling in dystrophic muscles. To address this hypothesis, 7‐week‐old mdx (diseased) and C57 (healthy) mice were fed a control diet (CD) or HF/HSD for 15 weeks, after which tissues were collected and analyzed. Data were compared using two‐way ANOVAs with Tukey adjustments and repeated measures ANOVA, with significance established at p&lt;0.05. Insulin resistance was confirmed in the HF/HSD groups via increased area under the curve following a glucose tolerance test (p&lt;0.05) and decreased rate of glucose disappearance following an insulin tolerance test (ITT; p&lt;0.05). Further, these outcomes also suggest IR in mdx‐CD compared to C57‐CD as glucose clearance was impaired following an ITT. Visceral adipose (peri‐renal and epididymal) was impacted by disease and diet such that it was lower in mdx mice than C57 and increased in HF/HSD compared to CD, with a significant interaction (p&lt;0.05). Of note, the perirenal adipose weights were increased almost 2‐fold in mdx‐HF/HSD compared to mdx‐CD. To probe for changes associated with both IR and DMD in skeletal muscle, we measured markers of inflammatory signaling using western blot. In whole muscle protein from the diaphragm, TLR4, a pattern recognition receptor, was increased approximately 70% by disease (p&lt;0.05) and 40% by HF/HSD (p&lt;0.05). TNFα, a pro‐inflammatory cytokine, had a significant interaction effect, was increased approximately 50% by disease (p&lt;0.05), decreased 28% by diet (p&lt;0.05), and mdx‐CD was higher (p&lt;0.05) than the other groups. NFκB, a transcription factor that regulates inflammatory responses, increased (p&lt;0.05) as a main effect of disease in whole muscle homogenate and nuclear fraction, but was not changed by diet. IκBα, an inhibitor of NFκB activation, and IKKα, an inhibitor of IκBα and promoter of NFκB, were increased by 1.6‐fold and 2‐fold, respectively (p&lt;0.05), as a function of disease but were resistant to changes caused by diet. AP1 was increased approximately 3‐fold (p&lt;0.05) with dystrophin deficiency in whole muscle homogenate but decreased in the nuclear fraction (45%, p&lt;0.05). In summary, we discovered a HF/HSD induced IR in mdx mice, and our data indicate IR may be a fundamental consequence of dystrophin deficiency. Further, counter to our hypothesis, we discovered that a HF/HSD did not promote inflammatory signaling in dystrophin‐deficient skeletal muscle.

Randomized double-blind placebo-controlled trial of Jingfang Granules in treatment of common cold(wind-cold syndrome)

Jingfang Granules have the effects of inducing sweating to releasing exterior, dispersing wind and dispelling dampness. Modern studies have demonstrated that it has antipyretic and antiviral activities. Therefore, this trial was conducted to evaluate the efficacy and safety of Jingfang Granules in the treatment of common cold(wind-cold syndrome). A total of 138 common cold(wind-cold syndrome) patients meeting the inclusion and exclusion criteria were randomly assigned into the experimental group(n=92) and the placebo group(n=46) at a ratio of 2∶1 and respectively received Jingfang Granules and Jingfang Granules simulation agent. The treatment lasted for 5 d, and the follow-up time was 8 d. Recovery time was employed as the main indicator of efficacy. The median reco-very time of the experimental group was 3.33 d, shorter than that 7.00 d of the placebo group. The efficacy of the experimental group was better than that of the placebo group(P&lt;0.000 1). The major symptom severity score-time AUC of the experimental group was 489.90±206.95, which was smaller than that of the placebo group(763.50±339.53). The recovery rate and marked effective rate of the experimental group were higher than those of the placebo group, The above outcomes were statistically significant between the two groups(P&lt;0.05). The disappearance time and rate of single symptoms including aversion to cold, nasal congestion, runny nose, cough, headache, pharyngeal itching/pain, white sputum, and somatalgia also had significant differences between the two groups(P&lt;0.05), indicating that Jingfang Granules had good performance in alleviating the above symptoms. During the study period, one case of the experimental group had a slight increase in serum creatinine, which returned to the normal level after re-examination. The incidence of adverse reactions was 1.10%, and no serious adverse reaction was found. The two groups had no significant difference in the incidence of adverse reactions. In conclusion, Jingfang Granules can significantly shorten the course of common cold(wind-cold syndrome) and quickly alleviate the clinical symptoms, demonstrating good safety and clinical advantages.

Early effects of Roux-en-Y gastric bypass on dietary fatty acid absorption and metabolism in people with obesity and normal glucose tolerance.

Roux-en-Y gastric bypass (RYGB) surgery markedly increases the rate of intestinal nutrient exposure after food intake, accelerates intestinal absorption of dietary glucose and protein, and alters the postprandial gut hormone response. However, our understanding of postprandial fat absorption and metabolism after RYGB is incomplete. Stable palmitate tracers were administered intravenously (K-[2,2-2H2]palmitate) and orally with a mixed meal ([U-13C16]palmitate) to study fatty acid absorption and metabolism before and 3 months after RYGB in 10 participants with obesity and normal glucose tolerance. There was a tendency toward reduced fasting plasma nonesterified palmitate concentrations after RYGB, but neither fasting palmitate kinetics nor fasting triacylglycerol (TAG) concentrations changed compared with before surgery. Postprandial TAG concentrations were numerically, but nonsignificantly, reduced 3-4 h after meal intake after compared with before RYGB. However, the postprandial appearance of the oral palmitate tracer in the plasma TAG pool and overflow into the nonesterified palmitate pool were initially faster but overall reduced after RYGB by 50% (median, IQR: [47;64], P = 0.004) and 46% (median, IQR: [33;70], P = 0.041), respectively. The maximal postprandial suppression of plasma nonesterified palmitate concentrations was slightly greater but shorter lasting after RYGB ('time × visit' interaction: P < 0.001), without detectable effects of surgery on the rate of appearance and disappearance of plasma palmitate. RYGB resulted in an initially accelerated but overall ~50% reduced 4-h postprandial systemic appearance of dietary palmitate in participants with obesity and normal glucose tolerance. This is likely a result of faster but incomplete intestinal fat absorption combined with enhanced chylomicron-TAG clearance, but it needs further investigation in studies specifically designed to investigate these mechanisms.

Acupoint application for exogenous fever: a multi-central retrospective cohort study

To explore the effectiveness on exogenous fever and the characteristics of effective population, as well as the specialties of prescription of acupoint application. Using the internet electronic diagnosis and treatment platform (Spring Broadcast Wanxiangyun Clinic Database, and the main TCM suitable technology promoted by this platform is acupoint application therapy), from August 24, 2020 to November 5, 2020, the patients complained with fever and diagnosed as common cold, with a record of initial visit and at least one return visit, were included as the subjects. According to whether acupoint application therapy was received or not, the subjects were divided into an exposure group (with acupoint application therapy, 26 664 cases) and a non-exposure group (without acupoint application therapy, 515 cases). Using the propensity score, the mixed factors, e.g. age and sex, were matched between the two groups. The disappearance rate of fever (within 2 days) and the time for the first fever disappearance were taken as the effect indexes. The association rules extraction was adopted to analyze the characteristics of effective population and acupoint application prescription in treatment of exogenous fever. After propensity score matching, there were 1 229 cases in the application group and 423 cases in the non-application group. The disappearance rate of fever in the application group was 1.82 times as high as that in the non-application group (P<0.05). The time for the first fever disappearance in the application group was shorter than the non-application group (P<0.01). A total of 5 370 cases were effective with acupoint application therapy, of which, the median age was 2 years old and the proportion of children patients under 6 years old was relatively high. In the effective crowd, the most commonly-used acupoints were Shenque (CV 8), Dazhui (GV 14), Yongquan (KI 1) and Tiantu (CV 22), etc. Shenque (CV 8) and Dazhui (GV 14) were highly associated and the support was 62.57%. The most common herbal materials in the acupoint application therapy included Radix et Rhizoma Rhei, Natrii Sulfas, Radix Scutellariae, Herba Ephedrae and Radix Bupleuri, etc. Radix et Rhizoma Rhei and Natrii Sulfas were most commonly used at Shenque (CV 8) and the supports were 57.49% and 57.21% respectively. Herba Ephedrae was most commonly applied to Shenque (CV 8) and Dazhui (GV 14) and the supports were 48.21% and 43.91% respectively. Radix Bupleuri was the most common herb at Dazhui (GV 14) with the support of 46.61%. Besides, the most commonly combined western drugs included cefixime and keteling in the acupoint application therapy and the supports were 13.07% and 12.72% respectively. Acupoint application is effective on exogenous fever. The common therapy refers to Radix et Rhizoma Rhei and Natrii Sulfas plaster at Shenque (CV 8), while Herba Ephedrae and Radix Bupleuri at Dazhui (GV 14).

Efficacy and Safety of Zuojin Pill for the Treatment of Chronic Nonatrophic Gastritis: A Randomized Active-Controlled Clinical Trial.

Objective Zuojin pill (ZJP) is used as the classical prescription for a wide variety of digestive diseases. However, there is a lack of direct evidence for its use in the treatment of chronic nonatrophic gastritis (CNG). In particular, there is a lack of rigorous trials of randomized controlled designs. In this study, a randomized active-controlled clinical trial was performed to verify the efficacy and safety of ZJP in detail. Methods Patients with CNG were divided into the ZJP group and the Marzulene-S granule group. Patients were enrolled from September 2019 to February 2021 (ChiCTR2000040549). Endoscopy and histology scores were evaluated as the primary outcome measure. The Helicobacter pylori positive rate and the disappearance rate of symptoms were also measured to reflect the outcomes. Finally, adverse events were also calculated as the index of safety. Results A total of 68 eligible patients were enrolled in this trial and randomly divided into two groups with baseline comparability. ZJP was able to improve the red plaques as well as bile reflux scores compared with Marzulene-S granule (P=0.043 and P=0.019, respectively). Moreover, it also remarkably alleviated the active chronic inflammation score (P=0.043). However, there was no difference between the Helicobacter pylori positivity rate (P=0.752). The symptom scores of abdominal distension (P=0.004), belching (P=0.010), and loss of appetite (P=0.019) were alleviated by ZJP, but nausea and vomiting were not (P=0.616). ZJP can also be considered safe with no obvious adverse effects. Conclusion ZJP might decrease mucosal injury and alleviate symptoms in CNG. In addition, more large-scale clinical trials should be carried out to further confirm its clinical efficacy and safety.

The AR in bone marrow progenitor cells protects against short-term high-caloric diet-induced weight gain in male mice.

We previously identified a novel pathway of testosterone action via the androgen receptor (AR) in bone marrow mesenchymal precursor cells (BM-PCs) to negatively regulate fat mass and improve metabolic function in male mice. This was achieved using our PC-AR Gene Replacement mouse model in which the AR is only expressed in BM-PCs and deleted in all other tissues. We hypothesise that the markedly reduced fat mass and increased insulin sensitivity of PC-AR Gene Replacements will confer protection from diet-induced overweight and obesity. To test this, 6-week-old male PC-AR Gene Replacements and controls (WT, global-AR knockouts (KOs)) were fed a chow or high-caloric diet (HCD) for 8 or 18 weeks. Following 8 weeks (short-term) of HCD, WT and Global-ARKOs had markedly increased subcutaneous white adipose tissue (WAT) and retroperitoneal visceral adipose tissue (VAT) mass compared to chow-fed controls. In contrast, PC-AR Gene Replacements were resistant to WAT and VAT accumulation following short-term HCD feeding accompanied by fewer large adipocytes and upregulation of expression of the metabolic genes Acaca and Pnlpa2. Following long-term HCD feeding for 18 weeks, the PC-AR Gene Replacements were no longer resistant to increased WAT and VAT adiposity, however, maintained their improved whole-body insulin sensitivity with an increased rate of glucose disappearance and increased glucose uptake into subcutaneous WAT. In conclusion, the action of testosterone via the AR in BM-PCs to negatively regulate fat mass and improve metabolism confers resistance from short-term diet-induced weight gain and partial protection from long-term diet-induced obesity in male mice.

Efficacy and Safety of Thermal Ablation for Treating Lymph Node Metastasis From Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis.

ObjectiveTo evaluate the efficacy and safety of thermal ablation, including radiofrequency ablation (RFA), microwave ablation (MVA), and laser ablation (LA), for treating lymph node metastasis (LNM) from papillary thyroid carcinoma (PTC).Design and MethodsPubMed and EMBASE were searched for studies reporting the efficacy and safety of thermal ablation for treating LNM in PTC. After selecting the relevant literature (including 11 papers, 208 patients, 412 lymph nodes), the QUADAS-2 tool was used to evaluate its quality. Then, both the fixed-effects and random-effects models combined with subgroup analysis were used to calculate data on volume changes in metastatic lymph nodes and changes in serum thyroglobulin (Tg) levels. We pooled the proportion of major and overall complication rates and complete disappearance rates and used subgroup forest plots and funnel plots for visual representation. Because of publication bias, we also performed a trim-and-filled model for correction. The rate of recurrence and distant metastasis with ablated details were pooled.ResultsIn the 11 articles (208 patients and 412 diseased lymph nodes), all thermal ablation methods showed effectiveness in reducing lymph node volume (P = 0.02) and serum Tg levels (P < 0.01) which showed no between-group difference. The pooled proportion of major complications was 0%(95% CI: -0.14; 0.15, P = 1) and the overall complication rate was 5% (95% CI: -0.09; 0.20, P = 1), which revealed no significant difference among modalities. The pooled proportion of the complete disappearance rate was 82% (95% CI: 0.43; 0.96, P < 0.01) and the data with statistical significance which contains RFA and LA showed complete disappearance rate was 59% and 81% respectively.ConclusionAll thermal ablation methods, including RFA, MWA, and LA, were effective and safe for treating LNM in PTC and were especially suitable for nonsurgical patients. Besides, subgroup analysis showed no significant difference, except for LA is better than RFA in complete disappearance rate.

A multivariate Box-Behnken assessment of elevated branched-chain amino acid concentrations in reduced crude protein diets offered to male broiler chickens.

In a Box-Behnken assessment of elevated branched-chain amino acids (BCAA), 13 nutritionally equivalent maize-based diets were offered to a total of 390 off-sex male Ross 308 broiler chickens from 7 to 28 days post-hatch. The BCAA concentrations investigated in reduced-crude protein diets were 12.5, 15.5, 18.3 g/kg leucine (125, 155, 183); 8.9, 10.2, 12.5 g/kg valine (89, 102, 125) and 7.2, 8.9, 10.8 g/kg isoleucine (72, 89, 109), where their relativity to 11.0 g/kg digestible lysine are shown in parentheses. Determined parameters included growth performance, relative abdominal fat-pad weights, nutrient utilisation, apparent digestibility coefficients, disappearance rates of 16 amino acids and free amino acid systemic plasma concentrations. Increasing dietary leucine linearly depressed weight gain and quadratically influenced FCR where the estimated minimum FCR of 1.418 was with 14.99 g/kg leucine. Polynomial regression analysis and surface response curves of determined parameters were generated for significant (P < 0.05) BCAA variables, based on lack of fit (P > 0.005). Quadratic and cross-product responses were observed for weight gain, FCR, AME, AMEn, N retention and apparent digestibility of 13 amino acids. Relative fat-pad weights declined linearly with increasing isoleucine and valine. The lowest N retention was estimated at a combination of 15.25 and 10.50 g/kg leucine and valine respectively whilst the highest mean digestibility coefficient (0.793) of amino acids was estimated at a combination of 15.74 and 10.47 g/kg of leucine and valine respectively. The remaining parameter minima or maxima responses were not able to be determined since they were outside the extreme BCAA treatment levels. Increasing dietary BCAA significantly increased apparent ileal digestibilities and disappearance rates of BCAA. Systemic plasma concentrations of valine increased (P < 0.001) with increasing dietary valine but leucine was not influenced (P > 0.25). Systemic plasma concentration of isoleucine was maximised (P < 0.001) only when accompanied by elevated dietary leucine. Also, dietary treatments influenced (P < 0.05) apparent disappearance rates of all the essential amino acids analysed, with the exception of methionine. Whilst overall growth performance was not disadvantaged (P > 0.10) by elevated BCAA levels, compared with 2019 Ross 308 performance objectives, polynomial regression analysis suggested both interaction and antagonism between BCAA.

Effects of supplementation rate of an extruded dried distillers' grains cube fed to growing heifers on voluntary intake and digestibility of bermudagrass hay.

Our objectives were to 1) investigate the difference in chemical composition and disappearance kinetics between loose dried distillers' grains (DDG) and extruded DDG cubes and 2) evaluate the effects of supplementation rate of extruded DDG cubes on voluntary dry matter intake (DMI), rate and extent of digestibility, and blood parameters of growing beef heifers offered ad libitum bermudagrass (Cynodon dactylon) hay. To characterize the changes in chemical composition during the extrusion process, loose and extruded DDG were evaluated via near-infrared reflectance spectroscopy, and dry matter (DM) disappearance kinetics were evaluated via time point in situ incubations. Extruded DDG cubes had greater (P ≤ 0.01) contents of fat, neutral detergent insoluble crude protein, and total digestible nutrients, but lower (P ≤ 0.01) neutral and acid detergent fiber than loose DDG. Additionally, the DM of extruded DDG cubes was more immediately soluble (P < 0.01), had greater (P < 0.01) effective degradability and lag time, and tended (P = 0.07) to have a greater disappearance rate than loose DDG. In the 29-d supplementation rate study, 23 Charolais-cross heifers were randomly assigned to one of four supplemental treatments: 1) control, no supplement; 2) low, 0.90 kg DDG cubes per d; 3) intermediate, 1.81 kg DDG cubes per d; or 4) high, 3.62 kg DDG cubes per d. Titanium dioxide was used as an external marker to estimate fecal output and particulate passage rate (Kp). Blood was collected from each animal to determine supplementation effects on blood metabolites. Indigestible neutral detergent fiber was used as an internal marker to assess the rate and extent of hay and diet DM digestibility (DMD). Increasing supplementation rate increased Kp and total diet DMI linearly (P < 0.01), yet linearly decreased (P < 0.01) hay DMI. Hay DMD decreased quadratically (P < 0.01), while total diet DMD increased linearly (P < 0.01) with increased DDG cube inclusion. Supplemented heifers had greater (P = 0.07) blood urea nitrogen concentrations than control animals 4 h post-supplementation. Intermediate and high rates of supplementation resulted in lower (P < 0.01) serum nonesterified fatty acid concentrations post-supplementation than control heifers. Concentrations of serum glucose and lactate were greatest (P ≤ 0.06) 8 h post-supplementation. Our results suggest that extruded DDG cubes may be an adequate supplement for cattle consuming moderate-quality forage, and further research is warranted.

Influence of acupoint application on clinical use of antibiotics: a real world study of 1.23 million primary clinic patients

To observe the influence of acupoint application on the use of antibiotics in primary clinic practice, and explore the effect of acupoint application and its influence on the use of antibiotics based on common diseases in primary clinic (fever, cough, diarrhea, sore throat). With the help of the internet electronic diagnosis and treatment platform (the main TCM suitable technology promoted by this platform is acupoint application therapy), the diagnosis and treatment data of 1.23 million patients in 2 000 primary clinics from August 24, 2020 to March 31, 2021 were collected. The patients were divided into an application group (acupoint application treatment) and a non-application group (non-acupoint application treatment), and the proportion of antibiotic use in the two groups was compared. The propensity score was used to match age, gender, concomitant symptoms, diagnosed diseases and other confounding factors of treatment, and the disappearance rate of symptoms (fever, cough, diarrhea, sore throat) and the time to first disappearance of symptoms were compared between the two groups. A total of 1 230 923 patients were analyzed, including 1 048 382 cases in the application group, accounting for 85.2%; 182 541 cases in the non-application group, accounting for 14.8%. The most patients who used acupoint application treatment were 0-2 years old, followed by 3-6 years old, and the patients over 15 years old who did not use acupoint application treatment were the most. The proportion of antibiotic use in the application group was 2.4%, lower than that in the non-application group (44.2%, P<0.001). The proportion of antibiotic use in all ages of patients in the application group was lower than that in the non-application group (P<0.001). Among the common diseases in primary clinic (fever, cough, diarrhea and sore throat), the proportion of antibiotic use in the application group was lower than that in the non-application group (P<0.01); the disappearance rate of symptoms in the application group was higher than that in the non-application group, and the time to first disappearance of symptoms was shorter than that in the non-application group (P<0.001). Acupoint application has a certain influence on the use of antibiotics in primary clinic patients. In the treatment of common diseases, patients treated with acupoint application have better curative effect and lower proportion of antibiotic use.