Probiotics for the prevention of Hirschsprung-associated enterocolitis.

BACKGROUND: Hirschsprung-associated enterocolitis (HAEC) is a leading cause of serious morbidity and potential mortality in children with Hirschsprung's disease (HD). People with HAEC suffer from intestinal inflammation, and present with diarrhoea, explosive stools, and abdominal distension. Probiotics are live microorganisms with beneficial health effects, which can optimise gastrointestinal function and gut flora. However, the efficacy and safety of probiotic supplementation in the prevention of HAEC remains unclear. OBJECTIVES: To assess the effects of probiotic supplements used either alone or in combination with pharmacological interventions on the prevention of Hirschsprung-associated enterocolitis. SEARCH METHODS: We searched CENTRAL, PubMed, Embase, the China BioMedical Literature database (CBM), the World Health Organization International Clinical Trials Registry, ClinicalTrials.gov, the Chinese Clinical Trials Registry, Australian New Zealand Clinical Trials Registry, and Clinical Trials Registry-India, from database inception to 27 February 2022. We also searched the reference lists of relevant articles and reviews for any additional trails. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing probiotics and placebo, or any other non-probiotic intervention, for the prevention of HAEC were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias of the included studies; disagreements were resolved by discussion with a third review author. We assessed the certainty of evidence using the GRADE approach. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous outcomes. MAIN RESULTS: We included two RCTs, with a total of 122 participants. We judged the overall risk of bias as high. We downgraded the evidence due to risk of bias (random sequence generation, allocation concealment, and blinding) and small sample size. The evidence is very uncertain about the effect of probiotics on the occurrence of HAEC (OR 0.58, 95% CI 0.10 to 3.43; I² = 74%; 2 studies, 120 participants; very low-certainty evidence). We found one included study that did not measure serious adverse events and one included study that reported no serious adverse events related to probiotics. Probiotics may result in little to no difference between probiotics and placebo in relation to the severity of children with HAEC at Grade I (OR 0.66, 95% CI 0.14 to 3.16; I² = 25%; 2 studies, 120 participants; low-certainty evidence). The effects of probiotics on the severity of HAEC at Grade II are very uncertain (OR 1.14, 95% CI 0.01 to 136.58; I² = 86%; 2 studies, 120 participants; very low-certainty evidence). Similarly, the evidence suggests that probiotics results in little to no difference in relation to the severity of HAEC at Grade III (OR 0.43, 95% CI 0.05 to 3.45; I² = 0%; 2 studies, 120 participants; low-certainty evidence). No overall mortality or withdrawals due to adverse events were reported. Probiotics may result in little to no difference in the recurrence of episodes of HAEC compared to placebo (OR 0.85, 95% CI 0.24 to 3.00; 1 study, 60 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: There is currently not enough evidence to assess the efficacy or safety of probiotics for the prevention of Hirschsprung-associated enterocolitis when compared with placebo. The presence of low- to very-low certainty evidence suggests that further well-designed and sufficiently powered RCTs are needed to clarify the true efficacy of probiotics.

Development of a nomogram for predicting nasogastric tube-associated pressure injuries in intensive care unit patients.

Here, we aimed to build a nomogram model to estimate the probability of nasogastric tube-associated pressure injuries (NTAPIs) in intensive care unit(ICU)patients. This prospective cohort study included 219ICU patients with nasogastric tube between September 2019 and January 2020.Univariate and multivariate logistic regression analyses were used to develop the nomogram model. The resulting nomogram was tested for calibration, discrimination, and clinical usefulness. Of the included patients, 58 developed NTAPIs, representing an incidence rate of 26.5%. Binary logistic regression analysis revealed that the prediction nomogram included C-reactive protein, vasopressor use, albumin level, nasogastric tube duration, and Sequential Organ Failure Assessment score. The value of these predictors was again confirmed using theLasso regression analysis. Internal validation presented a good discrimination of the nomogram, with an area under the curve value of 0.850, and good calibration (Hosmer-Lemeshow test, P = 0.177). The decision curve analysis also demonstrated preferable net benefit along with the threshold probability in the prediction nomogram. The nomogram model can accurately predict the risk factors for NTAPIs, to formulate intervention strategies as early as possible to reduce NTAPI incidence.

Label-free quantitative proteomic analysis of functional changes of goat milk whey proteins subject to heat treatments of ultra-high-temperature and the common low-temperature.

This work investigated the functional changes in whey proteins obtained from goat milk subject to various temperature treatments. Ultra-high temperature instantaneous sterilization (UHTIS) caused less damage than the common low-temperature, whereas spray-drying treatment had the opposite effect. A total of 426 proteins were identified in UHTIS and control treatment groups, including 386 common proteins and 16 and 14 unique proteins. The UHTIS treatment upregulated 55 whey proteins while down-regulated 98. The UHTIS-treated whey proteins may upregulate three metabolic pathways but downregulate one. Overall, UHTIS only slightly impacted the composition and functions of whey proteins from goat milk compared to the common low-temperature treatments.

[Effect between felodipine plus irbesartan and felodipine plus metoprolol regimen on the sexual function in young and middle-aged women with hypertension].

OBJECTIVE: To compare the effects between felodipine plus irbesartan and felodipine plus metoprolol regimen on blood pressure and the sexual function in young and middle-aged hypertensive women. METHODS: In this prospective, randomized, parallelized, controlled and fixed combined therapy trial, 99 female patients (aged 18 to 60) with grade 1 and grade 2 hypertension (BP ≥ 140/90 mm Hg and < 179/109 mm Hg, 1 mm Hg = 0.133 kPa) were assigned to felodipine 5 mg q.d + irbesartan 150 mg q.d (F + I group, n = 49) and felodipine 5 mg q.d + metoprolol 47.5 mg q.d (F + M group, n = 50) group. Target blood pressure was < 140/90 mm Hg. The female sexual function index (FSFI) questionnaire, levels of serum estradiol and testosterone were assessed. Female sexual dysfunction was defined as a FSFI score of less than 25.5. Patients were followed up for 24 weeks. RESULTS: The rate of achieving blood pressure goal between 2 groups was similar at the 4th, 8th, 12th and 24th weeks respectively (42.9% vs. 62.0% at 4th week, 89.8% vs. 90.0% at 8th week, 93.9% vs. 94.0% at 12th week, 98.0% vs. 96.0% at 24th week, P > 0.05). Compared to baseline, scores for the items related to "desire" and "arousal" were significantly improved (P < 0.05), the level of the serum estradiol was significantly elevated [(50.3 ± 37.4) pg/L vs. (54.4 ± 10.8) pg/L before menopause, (18.4 ± 2.9) pg/L vs. (20.2 ± 3.1)pg/L after menopause, P < 0.05] and the level of the serum testosterone was significantly decreased [(722.8 ± 277.1) ng/L vs. (650.0 ± 156.0) ng/L before menopause, (841.2 ± 279.3) ng/L vs. (761.9 ± 197.8) ng/L after menopause, P < 0.05] in the F + I group, while scores for the items related to "sexual desire" and "lubrication" were statistically reduced (P < 0.01), the concentration of the serum estradiol was significantly reduced [(57.4 ± 9.7) pg/L vs. (51.1 ± 12.1) pg/L before menopause, (19.8 ± 2.3) pg/L vs. (17.8 ± 3.3) pg/L after menopause, P < 0.01] and the level of the serum testosterone was significantly increased [(775.6 ± 217.8) ng/L vs. (886.0 ± 186.4) ng/L before menopause, (812.5 ± 311.3) ng/L vs. (914.4 ± 300.2) ng/L after menopause, P < 0.01] in the F + M group. FSFI score was negatively correlated with age and systolic blood pressure levels. CONCLUSION: felodipine plus irbesartan or metoprolol for 24 weeks equally reduced blood pressure and the former regimen is superior to the latter on sexual function improvement in this patient cohort.

High efficient mammalian expression and secretion of a functional humanized single-chain Fv/human interleukin-2 molecules.

AIM: To construct and produce a recombinant bispecific humanized single-chain Fv (sFv) /Interleukin-2 (IL-2) fusion protein by using mammalian cells. METHODS: The sFv/IL-2 protein was genetically engineered, and transfected to mammalian cells to determine whether the mammalian protein folding machinery can produce and secrete active sFv/IL-2 with high efficiency. RESULTS: The fusion protein was constructed and high efficiently expressed with yields up to 102 +/- 4.2 mg/L in culture supernatant of the stably transfected 293 cell line. This recombinant fusion protein consisted of humanized variable heavy (V(H)) and light (V(L)) domains of monoclonal antibody (mAb) 520C9 directed against the human HER-2/neu (c-erbB2) proto-oncogene product p185, and human IL-2 connected by polypeptide linker. The fusion protein was shown to retain the immunostimulatory activities of IL-2 as measured by IL-2-dependent cell proliferation and cytotoxicity assays. In addition to its IL-2 activities, this fusion protein also possessed antigen-binding specificity against p185, as determined by indirect ELISA using p185 positive SKOV 3ip1 cells. CONCLUSION: The large-scale preparation of the recombinant humanized sFv antibody/IL-2 fusion protein is performed with 293 cells. The recombinant humanized sFv antibody/IL-2 fusion protein may provide an effective means of targeting therapeutic doses of IL-2 to p185 positive tumors without increasing systemic toxicity or immunogenicity.

A Randomized, Controlled Trial to Assess the Efficacy of Arthroscopic Debridement in Combination with Oral Medication Versus Oral Medication in Patients with Gouty Knee Arthritis.

Gouty knee arthritis refers to a form of inflammatory diseases caused by deposits of needle-like crystals of uric acid in knee joint. The aim of this study was to assess the efficacy and safety of arthroscopic debridement in combination with oral medication versus oral medication alone for the treatment of gouty knee arthritis. A total of 60 patients with gouty knee arthritis were randomized to receive either arthroscopic surgery in combination with oral medication or oral medication alone. Efficacy was assessed with the angle of motion, functions, and visual analog scale (VAS). These indices were measured prior to treatment and at 2, 4, 12, 24, and 48 weeks posttreatment. Surgery- and medication-related complications were observed. Significant differences in flexion and extension of the knee joint, lymphoma scores, and VAS were detected between the two groups at 2, 4, and 12 weeks posttreatment (P < 0.05) but not at weeks 24 and 48 posttreatment (P > 0.05) . Significant differences in these indices were detected at different time points in each group (P < 0.05), except between weeks 24 and 48 (P > 0.05). Arthroscopic surgery in combination with oral medication is superior to single oral medication in the flexion and extension of the knee joint, lymphoma scores, and pain relief (VAS) before 24 weeks, although no statistical differences were detected in the efficacy after 24 weeks, and in medication-related safety between the two groups. Although arthroscopic debridement cannot replace systemic uric acid-lowering treatments such as medication and dietary control, it is still an effective approach.

Quality assessment of clinical guidelines in China: 1993 - 2010.

BACKGROUND: Clinical practice guidelines (CPGs) play an important role in healthcare in China as well as in the world. However, the current status and trends of Chinese CPGs are unknown. The aim of this study was to systematically review the present situation and the quality of Chinese CPGs published in the peer-reviewed medical literature. METHODS: To identify Chinese CPGs, a systematic search of relevant literature databases (CBM, WANFANG, VIP, and CNKI) was performed for the period January 1978 to December 2010. We used the AGREE II instrument to assess the quality of the included guidelines. RESULTS: We evaluated 269 guidelines published in 115 medical journals from 1993 to 2010 and produced by 256 different developers. Only four guidelines (1%) described the systematic methods for searching and selecting the evidence, 14 (5%) guidelines indicated an explicit link between the supporting evidence and the recommendations, only one guideline used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Thirty-one guidelines (12%) mentioned updates and the average frequency of update was 5.5 years; none described a procedure for updating the guideline. From the assessment with the Appraisal of Guidelines for Research and Ecaluation II (AGREE II), the mean scores were low for the domains "scope and purpose" (19%) and "clarity of presentation" (26%) and very low for the other domains ("rigour of development" 7%, "stakeholder involvement" 8%, "applicability" 6% and "editorial independence" 2%). CONCLUSIONS: Compared with other studies on the quality of guidelines assessed with the AGREE instrument in other countries, Chinese CPGs received lower scores, which indicates a relatively poor quality of the guidelines. However, there was some increase over time.