Endoscopic polidocanol foam sclerobanding for the treatment of grade II-III internal hemorrhoids: A prospective, multi-center, randomized study.

BACKGROUND: Endoscopic rubber band ligation (ERBL) is a nonsurgical technique for the treatment of symptomatic internal hemorrhoids but is limited by recurrence and post-procedural pain. AIM: To evaluate satisfaction, long-term recurrence, and post-procedural pain in managing internal hemorrhoids using a combination of polidocanol foam sclerotherapy and ERBL. METHODS: This was a prospective, multicenter, randomized study. A total of 195 consecutive patients diagnosed with grade II-III internal hemorrhoids were enrolled from four tertiary hospitals and randomly divided into a cap-assisted endoscopic polidocanol foam sclerobanding (EFSB) or an ERBL group. All patients were followed-up for 12 months. Symptom-based severity and post-procedural pain were assessed using a hemorrhoid severity score (HSS) and a visual analog scale (VAS). Continuous variables were reported as medians and interquartile range. RESULTS: One hundred and ninety-five patients were enrolled, with 98 in the EFSB group. HSS was lower in the EFSB group than in the ERBL group at 8 weeks [4.0 (3.0-5.0) vs 5.0 (4.0-6.0), P = 0.003] and 12-month [2.0 (1.0-3.0) vs 3.0 (2.0-3.0), P < 0.001] of follow-up. The prolapse recurrence rate was lower in the EFSB group at 12 months (11.2% vs 21.6%, P = 0.038). Multiple linear regression analysis demonstrated that EFSB treatment [B = -0.915, 95% confidence interval (CI): -1.301 to -0.530, P = 0.001] and rubber band number (B = 0.843, 95%CI: 0.595-1.092, P < 0.001) were negatively and independently associated with the VAS score 24 hours post-procedure. The median VAS was lower in the EFSB group than in the ERBL [2.0 (1.0-3.0) vs 3.0 (2.0-4.0), P < 0.001]. CONCLUSION: Cap-assisted EFSB provided long-term satisfaction and effective relief from the recurrence of prolapse and pain 24 hours post-procedure.

Systematic development of a highly efficient cell factory for 5-aminolevulinic acid production.

The versatile applications of 5-aminolevulinic acid (5-ALA) across the fields of agriculture, livestock, and medicine necessitate a cost-efficient biomanufacturing process. In this study, we achieved the economic viability of biomanufacturing this compound through a systematic engineering framework. First, we obtained a 5-ALA synthase (ALAS) with superior performance by exploring its natural diversity with divergent evolution. Subsequently, using a genome-scale model, we identified and modified four key targets from distinct pathways in Escherichia coli, resulting in a final enhancement of 5-ALA titers up to 21.82 g/l in a 5-l bioreactor. Furthermore, recognizing that an imbalance of redox equivalents hindered further titer improvement, we developed a dynamic control system that effectively balances redox status and carbon flux. Ultimately, we collaboratively optimized the artificial redox homeostasis system at the transcription level with other cofactors at the feeding level, demonstrating the highest recorded performance to date with a titer of 63.39 g/l for the biomanufacturing of 5-ALA.

[Intraperitoneal injection of human-derived anti-c-Met single-chain antibody inhibits the growth of transplanted tumours in A549 lung adenocarcinoma-loaded mice].

Objective To verify the anti-tumor effect of the mesenchymal-epithelial transition single-chain antibody (Met scFv) on subcutaneously transplanted tumors in nude mice. Methods A tumor model was established in nude mice by subcutaneous injection of A549 lung adenocarcinoma cells. Once the tumors were formed, IRDye680 LT N-hydroxysuccinimide (NHS) ester-labeled Met scFv was administered intraperitoneally. Real-time monitoring was conducted using a small animal imager to observe the dynamic distribution of the antibody in tumor-bearing mice. The affinity between c-Met and the antibody in tumor cells was detected. Tumor volume changes were observed and the tumor growth curve were plotted following regular tail vein injections of Met scFv. Immunohistochemical staining was employed to determine whether Met scFv could effectively bind to the c-Met antigen in tumor tissues. Results The distribution of Met scFv in nude mice showed that it was primarily located in the peritoneal cavity within the first 3 hours. After approximately 48 hours, fluorescent signals began to accumulate in the tumor tissue. Immunohistochemical staining of the tumors revealed high expression of c-Met in the tumor tissues; regular tail vein injections of Met scFv significantly slowed down the growth of tumors in mice. Conclusion Met scFv specifically recognizes tumor cells in vivo and exhibites significant anti-tumor activity.

The prognostic role of lymphocyte-to-monocyte ratio in patients with resectable pancreatic cancer: a systematic review and meta-analysis.

Objectives: This systematic review and meta-analysis examined whether the lymphocyte-to-monocyte ratio (LMR) can serve as an indicator for predicting the prognosis of patients with resectable pancreatic cancer. Patients and Methods: This meta-analysis was registered with PROSPERO: CRD42023461260. A systematic literature search was conducted in the PubMed, Embase, Cochrane, and Web of Science databases up to September 2023 to assess whether LMR can predict the prognosis of patients with resectable pancreatic cancer. The outcomes measured included subgroup analyses of overall survival (OS) with hazard ratios (HR) and confidence intervals of geographical region, patient population, and LMR threshold. A sensitivity analysis was also performed for OS and HR and confidence intervals were calculated for recurrence-free survival (RFS). Results: A total of 14 eligible articles, comprising 4,019 patients, were included in the comprehensive analysis. The results of this comprehensive analysis indicate that LMR is a robust predictor of OS, demonstrating strong prognostic significance (HR = 0.55, 95% CI [0.44-0.69], I2 = 79%, P < 0.00001). This predictive significance extended to various types of pancreatic cancer, such as pancreatic ductal adenocarcinoma (HR = 0.73, 95% CI [0.57-0.93], I2 = 46%, P = 0.01), pancreatic neuroendocrine neoplasms (HR = 0.81, 95% CI [0.66-0.99], P = 0.04) and other subtypes (HR = 0.40, 95% CI [0.22-0.72], I2 = 89%, P < 0.00001), but not to pancreatic head cancer (HR = 0.46, 95% CI [0.16-1.13], I2 = 59%, P = 0.12). LMR retained its predictive value across different regions, including Asia (HR = 0.62, 95% CI [0.47-0.76], I2 = 68%, P < 0.0001), Europe (HR = 0.78, 95% CI [0.67-0.91], I2 = 0%, P = 0.002), and the Americas (HR = 0.14, 95% CI [0.08-0.24], I2 = 0%, P < 0.00001). Notably, both LMR cut-off values greater than or equal to three (HR = 0.62, 95% CI [0.47-0.82], I2 = 67%, P = 0.0009) and less than three (HR = 0.47, 95% CI [0.32-0.69], I2 = 85%, P = 0.0001) exhibited prognostic significance. The sensitivity analysis for OS confirmed the strong predictive value of LMR, whereas LMR did not exhibit predictive significance for RFS (HR = 0.35, 95% CI [0.09-1.32], I2 = 95%, P = 0.12). In both subgroups categorized by Newcastle-Ottawa Scale (NOS) scores of ≥7 (HR = 0.66, 95% CI [0.54-0.80], I2 = 53%, P = 0.04) and <7 (HR = 0.41, CI [0.23-0.72], I2 = 89%, P < 0.00001), LMR was demonstrated to have predictive value. Conclusion: Despite the observed heterogeneity and potential biases in the included studies, the findings of this study suggest that LMR may serve as a valuable predictor of OS in patients with resectable pancreatic cancer.

[A quality improvement project on reducing antibiotic use duration in very low birth weight preterm infants in the neonatal intensive care unit]. / é™ä½Žæ–°ç”Ÿå„¿é‡ç—‡ç›‘æŠ¤å®¤æžä½Žå‡ºç”Ÿä½“é‡æ—©äº§å„¿æŠ—ç”Ÿç´ ä½¿ç”¨æ—¶é—´çš„è´¨é‡æ”¹è¿›ç ”ç©¶.

OBJECTIVES: To develop effective measures to reduce antibiotic use duration in very low birth weight (VLBW) preterm infants in the neonatal intensive care unit through quality improvement methods. METHODS: The study population consisted of hospitalized VLBW preterm infants, with the percentage of hospitalization time during which antibiotics were used from November 2020 to June 2021 serving as the baseline. The specific quality improvement goal was to reduce the duration of antibiotic use. Factors affecting antibiotic use duration in preterm infants were analyzed using Pareto charts. Key drivers were identified, and specific interventions were formulated based on the stages of antibiotic use. Changes in the percentage of antibiotic use duration were monitored with run charts until the quality improvement target was achieved. RESULTS: From November 2020 to June 2021, the baseline antibiotic use duration percentage was 49%, with a quality improvement target to reduce this by 10% within 12 months. The Pareto analysis indicated that major factors influencing antibiotic duration included non-standard antibiotic use; delayed cessation of antibiotics when no infection evidence was present; prolonged central venous catheter placement; insufficient application of kangaroo care; and delayed progress in enteral nutrition. The interventions implemented included: (1) establishing sepsis evaluation and management standards; (2) educating medical staff on the rational use of antibiotics for preterm infants; (3) supervising the enforcement of antibiotic use standards during ward rounds; (4) for those without clear signs of infection and with negative blood cultures, discontinued the use of antibiotics 36 hours after initiation; (5) reducing the duration of central venous catheterization and parenteral nutrition to lower the risk of infection in preterm infants. The control chart showed that with continuous implementation of interventions, the percentage of antibiotic use duration was reduced from 49% to 32%, a statistically significant decrease. CONCLUSIONS: The application of quality improvement tools based on statistical principles and process control may significantly reduce the antibiotic use duration in VLBW preterm infants. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 736-742.

Motor and sensory impairment in survivors of childhood central nervous system (CNS) tumors in the St. Jude Lifetime Cohort (SJLIFE).

BACKGROUND: Survivors of childhood central nervous system (CNS) tumors can develop motor and sensory impairment from their cancer and treatment history. We estimated the prevalence of motor and sensory impairment in survivors compared with controls through clinical assessment and identified associated treatment exposures and functional, quality of life (QOL), and social outcomes. METHODS: Survivors of childhood CNS tumors from the St. Jude Lifetime Cohort (n = 378, median [range] age 24.0 [18.0-53.0] years, 43.4% female) ≥5 years from diagnosis and controls (n = 445, median [range] age 34.0 [18.0-70.0] years, 55.7% female) completed in-person evaluation for motor and sensory impairment using the modified Total Neuropathy Score. Impairment was graded by modified Common Terminology Criteria for Adverse Events. Multivariable models estimated associations between grade ≥2 motor/sensory impairment, individual/treatment characteristics, and secondary outcomes (function by Physical Performance Test, fitness by physiologic cost index, QOL by Medical Outcomes Survey Short Form-36 physical/mental summary scores, social attainment). RESULTS: Grade ≥2 motor or sensory impairment was more prevalent in survivors (24.1%, 95% Confidence Interval [CI] 19.8%-29.4%) than controls (2.9%, CI 1.4-4.5%). Among survivors, in multivariable models, motor impairment was associated with vinca exposure <15 mg/m2 versus none (OR 4.38, CI 1.06-18.08) and etoposide exposure >2036 mg/m2 versus none (OR 12.61, CI 2.19-72.72). Sensory impairment was associated with older age at diagnosis (OR 1.09, CI 1.01-1.16) and craniospinal irradiation versus none (OR 4.39, CI 1.68-11.50). There were lower odds of motor/sensory impairment in survivors treated in the year 2000 or later versus before 1990 (Motor: OR 0.29, CI 0.10-0.84, Sensory: OR 0.35, CI 0.13-0.96). Motor impairment was associated with impaired physical QOL (OR 2.64, CI 1.22-5.72). CONCLUSIONS: In survivors of childhood CNS tumors, motor and sensory impairment is prevalent by clinical assessment, especially after exposure to etoposide, vinca, or craniospinal radiation. Treating motor impairment may improve survivors' QOL.

Effect of NLRP3 gene knockdown on pyroptosis and ferroptosis in diabetic cardiomyopathy injury.

Diabetic cardiomyopathy (DCM) is a chronic disease caused by diabetes mellitus, which is recognized as a worldwide challenging disease. This study aimed to investigate the role and the potential mechanism of knocking down the NACHT-, LRR- and PYD domains-containing protein 3 (NLRP3), an inflammasome associated with onset and progression of various diseases, on high glucose or diabetes -induced cardiac cells pyroptosis and ferroptosis, two regulated non-necrosis cell death modalities discovered recent years. In the present study, both in vivo and in vitro studies were conducted simultaneously. Diabetic rats were induced by 55 mg/kg intraperitoneal injection of streptozotocin (STZ). Following the intraperitoneal injection of MCC950 (10 mg/kg), On the other hand, the DCM model in H9C2 cardiac cells was simulated with 35 mmol/L glucose and a short hairpin RNA vector of NLRP3 were transfected to cells. The results showed that in vivo study, myocardial fibers were loosely arranged and showed inflammatory cell infiltration, mitochondrial cristae were broken and the GSDMD-NT expression was found notably increased in the DM group, while the protein expressions of xCT and GPX4 was significantly decreased, both of which were reversed by MCC950. High glucose reduced the cell viability and ATP level in vitro, accompanied by an increase in LDH release. All of the above indicators were reversed after NLRP3 knockdown compared with the HG treated alone. Moreover, the protein expressions of pyroptosis- and ferroptosis-related fators were significantly decreased or increased, consistent with the results shown by immunofluorescence. Furthermore, the protective effects of NLRP3 knockdown against HG were reversed following the mtROS agonist rotenone (ROT) treatment. In conclusion, inhibition of NLRP3 suppressed DM-induced myocardial injury. Promotion of mitochondrial ROS abolished the protective effect of knockdown NLRP3, and induced the happening of pyroptosis and ferroptosis. These findings may present a novel therapeutic underlying mechanism for clinical diabetes-induced myocardial injury treatment.

Knockdown of LncRNA Lcn2-204 alleviates sepsis-induced myocardial injury by regulation of iron overload and ferroptosis.

Ferroptosis is an iron-dependent programmed cell death form resulting from lipid peroxidation damage, it plays a key role in organ damage and tumor development from various causes. Sepsis leads to severe host response after infection with high mortality. The long non-coding RNAs (LncRNAs) are involved in different pathophysiological mechanisms of multiple diseases. Here, we used cecal ligation and puncture (CLP) operation to mimic sepsis induced myocardial injury (SIMI) in mouse model, and LncRNAs and mRNAs were profiled by Arraystar mouse LncRNA Array V3.0. Based on the microarray results, 552 LncRNAs and 520 mRNAs were differentially expressed in the sham and CLP groups, among them, LncRNA Lcn2-204 was the highest differentially expressed up-regulated LncRNA. Iron metabolism disorder was involved in SIMI by bioinformatics analysis, meanwhile, myocardial iron content and lipocalin-2 (Lcn2) protein expressions were increased. The CNC network comprised 137 positive interactions and 138 negative interactions. Bioinformatics analysis showed several iron-related terms were enriched and six genes (Scara5, Tfrc, Lcn2, Cp, Clic5, Ank1) were closely associated with iron metabolism. Then, we constructed knockdown LncRNA Lcn2-204 targeting myocardium and found that it ameliorated cardiac injury in mouse sepsis model through modulating iron overload and ferroptosis. In addition, we found that LncRNA Lcn2-204 was involved in the regulation of Lcn2 expression in septic myocardial injury. Based on these findings, we conclude that iron overload and ferroptosis are the key mechanisms leading to myocardial injury in sepsis, knockdown of LncRNA Lcn2-204 plays the cardioprotective effect through inhibition of iron overload, ferroptosis and Lcn2 expression. It may provide a novel therapeutic approach to ameliorate sepsis-induced myocardial injury.

[Significance and application of quality improvement in clinical medicine]. / 质量改进在临床医学中的意义和应用.

Quality improvement is a methodology which was initially developed and employed in the field of industrial manufacturing. This approach involves implementing a series of interventions aimed at elevating the existing quality standards to a higher level. In daily medical work, there are often spontaneous quality improvements. Medical quality improvements supported by scientific methodology can evaluate medical quality more scientifically and provide objective feedback on the quality of medical work for healthcare professionals. This article provides a concise introduction to quality improvement and shows its application and significance in the field of clinical medicine through examples.

Analysis of clinical evidence on traditional Chinese medicine for the treatment of diabetic nephropathy: a comprehensive review with evidence mapping.

Objective: This study aims to map evidence from Randomized Controlled Trials (RCTs) and systematic reviews/Meta-analyses concerning the treatment of Diabetic Nephropathy (DN) with Traditional Chinese Medicine (TCM), understand the distribution of evidence in this field, and summarize the efficacy and existing problems of TCM in treating DN. The intention is to provide evidence-based data for TCM in preventing and treating DN and to offer a reference for defining future research directions. Methods: Comprehensive searches of major databases were performed, spanning from January 2016 to May 2023, to include clinical RCTs and systematic reviews/Meta-analyses of TCM in treating DN. The analysis encompasses the publishing trend of clinical studies, the staging of research subjects, TCM syndrome differentiation, study scale, intervention plans, and outcome indicators. Methodological quality of systematic reviews was evaluated using the AMSTAR (Assessment of Multiple Systematic Reviews) checklist, and evidence distribution characteristics were analyzed using a combination of text and charts. Results: A total of 1926 RCTs and 110 systematic reviews/Meta-analyses were included. The majority of studies focused on stage III DN, with Qi-Yin deficiency being the predominant syndrome type, and sample sizes most commonly ranging from 60 to 100. The TCM intervention durations were primarily between 12-24 weeks. Therapeutic measures mainly consisted of Chinese herbal decoctions and patented Chinese medicines, with a substantial focus on clinical efficacy rate, TCM symptomatology, and renal function indicators, while attention to quality of life, dosage of Western medicine, and disease progression was inadequate. Systematic reviews mostly scored between 5 and 8 on the AMSTAR scale, and evidence from 94 studies indicated potential positive effects. Conclusion: DN represents a significant health challenge, particularly for the elderly, with TCM showing promise in symptom alleviation and renal protection. Yet, the field is marred by research inconsistencies and methodological shortcomings. Future investigations should prioritize the development of standardized outcome sets tailored to DN, carefully select evaluation indicators that reflect TCM's unique intervention strategies, and aim to improve the robustness of clinical evidence. Emphasizing TCM's foundational theories while incorporating advanced scientific technologies will be essential for innovating research methodologies and uncovering the mechanisms underlying TCM's efficacy in DN management.

Evidence mapping of traditional Chinese medicine in diabetic peripheral neuropathy treatment.

Objective: Diabetic peripheral neuropathy (DPN) stands as a crucial complication of diabetes, significantly affecting patients' quality of life. This study aims to elucidate the evidence distribution from clinical randomized controlled trials (RCTs) on DPN treatment with traditional Chinese medicine (TCM) through evidence mapping. Methods: A comprehensive search was conducted from January 2017 to October 2022 in databases such as Wanfang (China Online Journals), CNKI (China National Knowledge Infrastructure), VIP (China Science and Technology Journal Database), SinoMed (Chinese Biomedical Literature Database), PubMed, Web of Science, and Cochrane Library. Literature related to the treatment of DPN with TCM was selected. From the 1,229 RCTs identified over the past 6 years, relevant data were extracted. The evidence mapping approach was utilized, and trends in publications, study scales, intervention types, and evaluation indicators were analyzed using descriptive text combined with tables and bubble charts. Results: Research on the treatment of DPN with TCM is extensive. The publication trend remains relatively stable with predominantly smaller sample sizes. The main treatments encompass oral Chinese medicine and traditional external treatments. The most common evaluation indicators are neurophysiological, efficiency rate, symptom signs, neuropathy scores, and traditional Chinese symptoms, with less focus on psychological status and the ankle-brachial index (ABI). Conclusion: Shedding light on contemporary research, this study explores the current RCTs evaluating TCM's efficacy in treating DPN. The findings not only highlight the potential role of TCM in addressing diabetic complications but also underscore areas that could benefit from refined research approaches, expanded intervention methods, and broader assessment criteria. Our observations aim to inform and inspire future research directions and clinical practices concerning TCM's role in managing diabetes-associated complications.

Cardiac remodeling in patients with atrial fibrillation reversing bradycardia-induced cardiomyopathy: A case report.

BACKGROUND: Bradycardia-induced cardiomyopathy (BIC), which is a disease resulting from bradycardia, is characterized by cardiac chamber enlargement and diminished cardiac function. The correction of bradycardia can allow for significant improvements in both cardiac function and structure; however, this disease has been infrequently documented. In this case, we conducted a longitudinal follow-up of a patient who had been enduring BIC for more than 40 years to heighten awareness and prompt timely diagnosis and rational intervention. CASE SUMMARY: A woman who presented with postactivity fatigue and dyspnea was diagnosed with bradycardia at the age of 7. Since she had no obvious symptoms, she did not receive any treatment to improve her bradycardia during the 42-year follow-up, except for the implantation of a temporary pacemaker during labor induction surgery. As time progressed, the patient's heart gradually expanded due to her low ventricular rate, and she was diagnosed with BIC. In 2014, the patient developed atrial fibrillation, her ventricular rate gradually increased, and her heart shape gradually returned to normal. This report describes the cardiac morphological changes caused by the heart rate changes in BIC patients older than 40 years, introduces another possible outcome of BIC, and emphasizes the importance of early intervention in treating BIC. CONCLUSION: BIC can induce atrial fibrillation, causing an increased ventricular rate and leading to positive cardiac remodeling.

Efficacy and pharmacoeconomic advantages of Fufang Huangbai Fluid hydropathic compress in diabetic foot infections: a comparative clinical study with antimicrobial calcium alginate wound dressing.

Objective: To compare the intervention effects and pharmacoeconomic advantages of Fufang Huangbai Fluid (FFHB) hydropathic compress versus Antimicrobial Calcium Alginate Wound Dressing (ACAWD) in the treatment of diabetic foot infections (DFI). Methods: Patients with DF who were hospitalized in the peripheral vascular Department of Dongzhimen Hospital of Beijing University of Chinese Medicine from December 2020 to February 2022 and met the inclusion and excluding criteria were allocated into the experimental group and control group through minimization randomization. The experimental group was treated with FFHB hydropathic compress for 2 weeks, while the control group was treated with ACAWD for the same duration. The wound healing of both groups was monitored for 1 month post-discharge. Clinical data from all eligible patients were collected, and differences in various indices between cohorts were analyzed. Results: 22 in the experimental group (including two fell off) and 20 in the control group. After the treatment, the negative rate of wound culture in the experimental group was 30% and that in the control group was 10%, There was no significant difference in the negative rate of wound culture and change trend of minimum inhibitory concentration (MIC) value of drug sensitivity (p > 0.05). The infection control rate of the experimental group was 60%, and that of the control group was 25%. The difference between the two groups was statistically significant (χ2 = 5.013, p = 0.025). The median wound healing rate of the experimental group was 34.4% and that of the control group was 33.3%. There was no significant difference between the two groups (p > 0.05). During the follow-up 1 month later, the wound healing rate in the experimental group was higher, and the difference was statistically significant (p = 0.047). Pharmacoeconomic evaluations indicated that the experimental group had greater cost-effectiveness compared to the control group. Conclusion: In the preliminary study, FFHB demonstrated comparable pathogenic and clinical efficacy to ACAWD in the treatment of mild DF infection, and exhibited superior pharmacoeconomic advantages. With the aid of infection control, the wound healing rate in the FFHB group showed notable improvement. Nevertheless, due to the limited sample size, larger-scale studies are warranted to further validate these findings. Clinical Trial Registration: (https://www.chictr.org.cn/showproj.aspx?proj=66175), identifier (ChiCTR2000041443).

Using a new human milk fortifier to optimize human milk feeding among very preterm and/or very low birth weight infants: a multicenter study in China.

BACKGROUND: Human milk fortifier (HMF) composition has been optimized recently. But clinical evidence of its safety and efficacy is limited in Chinese population. The aim of this study was to evaluate effects of a new HMF in growth, nutritional status, feeding intolerance, and major morbidities among very preterm (VPT) or very low birth weight (VLBW) infants in China. METHODS: VPT/VLBW infants admitted from March 2020 to April 2021 were prospectively included in the experimental (new HMF, nHMF) group, who received a new powdered HMF as a breast milk feeding supplement during hospitalization. Infants in the control group (cHMF) admitted from January 2018 to December 2019, were retrospective included, and matched with nHMF group infants for gestational age and birth weight. They received other kinds of commercially available HMFs. Weight gain velocity, concentrations of nutritional biomarkers, incidence of major morbidities, and measures of feeding intolerance were compared between the two groups. RESULTS: Demographic and clinical characteristics of infants in nHMF and cHMF groups were comparable. Weight gain velocity had no significant difference between the nHMF (14.0 ± 3.5 g/kg/d) and the cHMF group (14.2 ± 3.8 g/kg/d; P = 0.46). Incidence of morbidities, including necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, culture-confirmed sepsis, and feeding intolerance during hospitalization between nHMF and cHMF, were similar (all P-values > 0.05). The time to achieve full enteral feeding [13.5 (10, 21) days] in the nHMF group was significantly shorter than that in the cHMF group [17 (12, 23) days, HR = 0.67, 95%CI: 0.49, 0.92; P = 0.01]. Compared with cHMF group, the decrease of blood urea nitrogen level over time in nHMF group was smaller (ß = 0.6, 95%CI:0.1, 1.0; P = 0.01). CONCLUSIONS: The new HMF can promote growth of preterm infants effectively without increasing the incidence of major morbidity and feeding intolerance. It can be used feasible in Chinese VPT/VLBW infants. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (NCT04283799).

High-risk groups of neonatal lupus erythematosus in term infants: a birth cohort study.

This study aims to analyze the clinical characteristics and risk factors of high-risk groups of neonatal lupus erythematosus (NLE) in term infants. High-risk groups of NLE infants whose mothers were positive for anti-SSA, anti-SSB or anti-U1RNP antibodies during pregnancy were enrolled. They were born between February 2013 and February 2020, with a gestational age not less than 37 weeks. We analyzed their clinical data from birth to 24 months after birth. A total of 105 patients in the NLE high-risk group were included. Among them, 30 patients were diagnosed with NLE (NLE group), and 75 patients were not (non-NLE group). The affected systems of the NLE group included the dermal (13.3%), hepatic (76.0%), and hematological systems (43.3%). Hepatic involvement, anemia and thrombocytopenia did not emerge until 60 days, 41 days and 22 days after birth, respectively, in some cases. Systemic involvement could be cured within 3 to 12 months after birth. The clearance time of specific autoantibodies was 12 months after birth. There was no significant difference in the clinical characteristics of babies and their mothers between the two groups, neither in the positive rate nor in the clearance time of specific autoantibodies. CONCLUSION: After standardized prenatal health care, there is still a high risk of dermal, hepatic, or hematological system involvement for high-risk groups of NLE. There are no specific indicators for the prediction of whether babies will develop NLE. All of these patients need to be followed up closely within one year after birth. WHAT IS KNOWN: • Neonatal lupus erythematosus (NLEs) can affect the cardiac, dermal, hepatic, and hematological systems of infants. WHAT IS NEW: • After standardized prenatal health care employing good multidepartment cooperation in our center, no neonates had cardiac block in this study. However, dermal, hepatic, and hematological system involvement of NLE can still gradually appear (as long as 60 days after birth in some cases) during follow-up, and some of these conditions are serious and require timely and active intervention. No single factor has been found to predict whether offspring at high-risk of NLE whose mothers are positive for anti-SSA, SSB and/or RNP will develop NLE.

Amino acid-based enteral nutrition is effective for pediatric Crohn's disease: a multicenter prospective study.

Background: Exclusive enteral nutrition (EEN) therapy effectively induces remission in pediatric Crohn's disease (CD). However, this may depend on the type of enteral formula used. Moreover, data on the efficacy of amino acid-based EEN are limited. Thus, we aimed to prospectively evaluate the efficacy of amino acid-based formulas for EEN in pediatric patients with active CD. Methods: Patients with active CD aged between 6 and 17 years were recruited into this prospective study from four hospitals in China between March 2019 and December 2021. Patients received EEN for 8 weeks. Inflammatory and nutrition-associated indices were evaluated at 0, 4, and 8 weeks after treatment. Paired t-tests and Wilcoxon signed-rank tests were used to compare continuous and categorical variables before and after intervention, respectively. Results: Twenty-four patients were included in the analysis. After an 8-week intervention period, the CD activity index significantly decreased (26.3 ± 12.2 vs 7.1 ± 8.3, P < 0.001). Most patients (66.7%) achieved complete clinical remission. Among the 22 patients who had ulcers and erosions diagnosed endoscopically at baseline, 10 (45.5%) achieved complete mucosal healing. The degree of thickening of the intestinal wall was significantly reduced after EEN intervention, with a transmural healing rate of 42.9%. Furthermore, the serum inflammatory markers decreased and there was a significant improvement in the nutrition-related indices (P < 0.05). There were no severe adverse effects. Conclusions: Amino acid-based EEN is effective and safe for treating pediatric-onset CD. Studies with larger sample sizes and mechanistic and follow-up studies are required to further validate these findings.

Restoration of saturated outputs from microchannel plate photomultiplier tubes in sub-microsecond single-pulse-current mode.

Microchannel plate (MCP) photomultiplier tubes (PMTs) are frequently used in experimental diagnostics, where they are operated in single-pulse current measurement mode. However, considering the significant amplitude fluctuations in the measured signal, the resulting output signal from the MCP-PMT is inevitably distorted by gain saturation. Therefore, understanding the correlation between the MCP-PMT output signal and gain saturation is critical in assessing the extent of output signal distortion and determining the MCP-PMT saturation level. This knowledge allows for a more precise assessment of the input signal's features. In this paper, we present an experimental method for restoring the initial waveform from the saturated MCP-PMT signal. To correct the amplitude-drop caused by gain saturation, our technique involves calibrating the MCP-PMT's relative gain as a function of the accumulated output charge using a square-wave light source. We then applied this approach to restore a ∼500 ns saturated pulse from a double-layer 10 mm diameter MCP-PMT. The restored signal showed a deviation of less than 6% from the reference waveform, which validates the effectiveness of the technique.

Mapping the path towards novel treatment strategies: a bibliometric analysis of Hashimoto's thyroiditis research from 1990 to 2023.

Background: Hashimoto's thyroiditis (HT), a common form of thyroid autoimmunity, is strongly associated with deteriorating clinical status and impaired quality of life. The escalating global prevalence, coupled with the complexity of disease mechanisms, necessitates a comprehensive, bibliometric analysis to elucidate the trajectory, hotspots, and future trends in HT research. Objective: This study aims to illuminate the development, hotspots, and future directions in HT research through systematic analysis of publications, institutions, authors, journals, references, and keywords. Particular emphasis is placed on novel treatment strategies for HT and its complications, highlighting the potential role of genetic profiling and immunomodulatory therapies. Methods: We retrieved 8,726 relevant documents from the Web of Science Core Collection database spanning from 1 January 1990 to 7 March 2023. Following the selection of document type, 7,624 articles were included for bibliometric analysis using CiteSpace, VOSviewer, and R software. Results: The temporal evolution of HT research is categorized into three distinct phases: exploration (1990-1999), rapid development (1999-2000), and steady growth (2000-present). Notably, the United States, China, Italy, and Japan collectively contributed over half (54.77%) of global publications. Among the top 10 research institutions, four were from Italy (4/10), followed by China (2/10) and the United States (2/10). Recent hotspots, such as the roles of gut microbiota, genetic profiling, and nutritional factors in HT management, the diagnostic dilemmas between HT and Grave's disease, as well as the challenges in managing HT complicated by papillary thyroid carcinoma and type 1 diabetes mellitus, are discussed. Conclusion: Although North America and Europe have a considerable academic impact, institutions from emerging countries like China are demonstrating promising potential in HT research. Future studies are anticipated to delve deeper into the differential diagnosis of HT and Grave's disease, the intricate relationship between gut microbiota and HT pathogenesis, clinical management of HT with papillary thyroid carcinoma or type 1 diabetes, and the beneficial effects of dietary modifications and micronutrients supplementation in HT. Furthermore, the advent of genetic profiling and advanced immunotherapies for managing HT offers promising avenues for future research.

Effects of Radiation Therapy on the Female Reproductive Tract in Childhood Cancer Survivors: A PENTEC Comprehensive Review.

PURPOSE: The PENTEC (Pediatric Normal Tissue Effects in the Clinic) task force aimed to quantify effects of radiation therapy (RT) dose to the female reproductive organs after treatment for childhood cancer. METHODS AND MATERIALS: Relevant studies published 1970 to 2017 were identified systematically through PubMed, Medline, and Cochrane databases with additional articles before 2021 identified by the group. Two large studies reported sufficient data to allow modeling of acute ovarian failure (AOF; loss of function ≤5 year from diagnosis) and premature ovarian insufficiency (POI; loss of function at attained age <40 years) based on maximum dose to least affected ovary. Although normal tissue complication probability modeling was not feasible for the uterus due to limited data, the relationship between ultrasound-measured uterine volume and estimated amount of RT was plotted. Limited data regarding vaginal toxicity were available. RESULTS: The risk of AOF increases with RT dose to least affected ovary, alkylating agent cumulative dose (cyclophosphamide equivalent dose [CED] in g/m2), age at RT, and stem cell transplantation: Two Gy to the least affected ovary resulted in AOF risk of 1% to 5% (CED = 0, risk increasing with age), 4% to 7% (CED = 10 g/m2, risk increasing with age), and 6% to 13% (CED = 30 g/m2, risk increasing with age). For patients aged 1 and 20 years at time of RT, AOF risk was ≥50% at doses of 24 Gy and 20 Gy with no alkylating chemotherapy, 22.5 Gy and 17 Gy with intermediate alkylator dose (10 g/m2), and 17 Gy and 13 Gy with high alkylator dose (30 g/m2). Risk of POI increases with survivor (attained) age (rather than age at time of RT), radiation dose to least affected ovary, and alkylator dose. Data review suggested that higher radiation doses to the uterus are associated with uterine toxicity, with uterine size considerably restricted after 12 Gy. Vaginal radiation in children is associated with high toxicity risk, although dose-volume data are not available for quantification. CONCLUSIONS: Risk of AOF increases with age at RT, CED exposure, and RT dose; risk of POI likewise increases with RT dose, CED exposure, and survivor age. Both AOF and POI are expected to affect fertility and estrogen production. Data suggest that RT uterine dose >12 Gy may be associated with uterine size restriction. Adult literature suggests that maintaining vaginal dose <5 Gy may limit toxicity. Treatment of life-threatening malignancy remains a priority over reproductive preservation; however, when possible, radiation and surgical techniques should be considered to minimize dose to least affected ovary, uterus, and vagina. Survivors should receive endocrine and gynecologic support; those desiring pregnancy should be counseled early to maximize reproductive options.

Role of Pediatricians in Promoting and Supporting Breastfeeding: A Position Paper of the International Pediatric Association Strategic Advisory Group on Infant, Child, and Adolescent Nutrition.

BACKGROUND: Promoting and supporting breastfeeding is an important public health intervention with multiple benefits for both infants and mothers. Even modest increases in the prevalence and duration of breastfeeding could significantly reduce healthcare costs and improve maternal and child health outcomes. However, widespread adoption of breastfeeding recommendations remains poor in most settings, which contributes to widening health and social inequalities. Pediatricians have a duty to advocate for improving child health, including promoting and supporting breastfeeding. SUMMARY: This paper, from the International Pediatric Association Special Advisory Group on Nutrition, considers common barriers to breastfeeding and addresses how pediatricians can better promote and support breastfeeding, both at an individual level and by influencing practice and policy. All pediatricians need to understand the basics of breastfeeding, including lactation physiology, recognize common breastfeeding problems, and advise mothers or refer them for appropriate support; training curricula for general pediatricians and all pediatric subspecialties should reflect this. Even in the situation where their day-to-day work does not involve direct contact with mothers and infants, pediatricians can have an important influence on policy and practice. They should support colleagues who work directly with mothers and infants, ensuring that systems and environments are conducive to breastfeeding and, where appropriate, milk expression. Pediatricians and pediatric organizations should also promote policies aimed at promoting and supporting breastfeeding at local, regional, national, and international levels. KEY MESSAGES: Pediatricians have a duty to promote and support breastfeeding, regardless of their day-to-day role and responsibilities. Pediatric training curricula should ensure that all trainees acquire a good understanding of breastfeeding so they are able to effectively support mothers in their personal practice but also influence breastfeeding practice and policy at a local, regional, national, and international level.