Objective To explore the efficacy and safety of oral solution of magnesium sodium potassium sulfate in bowel preparation before colonoscopy. Methods Patients who planned to undergo colonoscopy at the digestive department of the Ninth People’s Hospital, affiliated to School of Medicine of Shanghai Jiao Tong University from January 2023 to August 2023 were selected and eligible subjects were divided into two groups: Group A took polyethylene glycol （PEG） and Group B took oral solution of magnesium sodium potassium sulfate （OSS）. The quality, drug tolerance, and safety of intestinal preparation were evaluated. The quality of bowel preparation was evaluated by the boston bowel preparation scale （BBPS）. Results The right colon BBPS score of Group B was (2.39±0.82) points, which was significantly higher than of Group A (2.11±0.43) points （P<0.05）. The overall score of Group B was higher than that of Group A （P<0.05）. OSS was easier to take than PEG, with a good taste and overall sensation. Patients were willing to use OSS to clean their bowels even when they were willing to undergo another examination （P<0.05）. There was a significant difference in nausea and vomiting symptoms between the two groups （P<0.05）, and there were no significant changes in renal function and electrolytes before and after medication in the two groups of patients. Conclusion OSS had a higher quality of bowel cleaning and was easier for patients to accept.

Objective To preliminarily investigate the safety and efficacy of donor pancreas needle biopsy in simultaneous pancreas-kidney transplantation. Methods Clinical data of 7 cases undergoing donor pancreas biopsy were collected retrospectively. All cases underwent donor pancreas biopsy before or during simultaneous pancreas-kidney transplantation. Frozen section or paraffin sectioning techniques were used for tissue preparation, and hematoxylin-eosin and Masson staining were performed to histologically evaluate the donor pancreas. The quality of donor pancreas was comprehensively assessed by combining histological findings with the donor's clinical data. Postoperative follow-up data of 5 simultaneous pancreas-kidney transplant recipients were collected to summarize the safety of donor pancreas biopsy and the prognosis of transplant recipients. Results The 7 pancreas donors were aged 28 to 62 years, with a body mass index ranging from 20.76 to 27.68 kg/m². Liver ultrasound indicated fatty liver in 3 cases, while pancreatic ultrasound did not reveal any significant abnormalities. Among them, biopsy was performed on 2 donors after completion of pancreatic procurement and processing, and the frozen section histology showed moderate acute pancreatitis changes (edema of acinar cells, necrosis and inflammatory cell infiltration). Combined with a serum amylase level elevated more than 3 times the upper limit of normal value, these two donor pancreases were finally discarded. The remaining 5 cases underwent biopsy immediately after pancreatic vascular anastomosis during simultaneous pancreas-kidney transplantation, and histological evaluation was performed on paraffin-embedded sections. No biopsy-related complications (such as bleeding, pancreatic fistula, etc.) occurred after transplantation. One recipient died of severe infection 2 months after transplantation, while the other 4 recipients were followed up for more than 5 years, with well-functioning transplant kidneys and pancreases. Conclusions Donor pancreas biopsy is relatively safe, and the risk of biopsy-related complications after transplantation is controllable. Comprehensive assessment of donor pancreas quality by combining histological evaluation with the donor's clinical indicators is conducive to improving the accuracy of donor pancreas selection and organ utilization.

Background Lead is a typical persistent environmental pollutant that can accumulate in bones for decades. During pregnancy, alterations in calcium metabolism promote the mobilization of bone lead, resulting in secondary exposure; however, the mechanisms by which pregnancy-associated bone lead mobilization affects maternal renal function remain unclear. Objective To investigate the role of mitochondrial dysfunction in pregnancy-related bone lead mobilization-induced renal injury. Methods Newly weaned female Wistar rats were randomly assigned to a control or a lead-exposed group administered either 0.05% sodium acetate or 0.05% lead acetate in drinking water. Following a 4-week lead exposure and a 4-week washout period, the females were co-housed with healthy age-matched males for mating. Rats were sacrificed at early (gestational day 3) and late (gestational day 17) pregnancystages, respectively. Renal histopathology was assessed using hematoxylin and eosin staining staining. Mitochondria-related indicators, including oxidative stress, inflammatory responses, and energy metabolism, were measured. Differential metabolites were identified using serum metabolomics. Results Renal injury in the lead-exposed pregnant rats progressed in a time-dependent manner, characterized by degeneration of proximal tubular epithelial cells, glomerular hyaline changes, and interstitial inflammatory cell infiltration. Repeated measures ANOVA indicated a significant interaction between the treatment factor (lead exposure) and the temporal factor (gestational stage) on renal injury (P<0.001). Further analysis of mitochondrial function-related indicators in late-pregnancy renal tissue revealed that the lead exposure group exhibited significantly increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) (P<0.05), accompanied by a reduction in superoxide dismutase (SOD) and reduced glutathione (GSH) activities (P<0.05); regarding inflammatory markers, levels of interleukin-18 (IL-18) and interleukin-1β (IL-1β) were elevated (P<0.01), whereas interleukin-33 (IL-33) was decreased in the lead-exposed group (P<0.05); energy metabolism-related indicators, including adenosine triphosphate (ATP) level, Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities, and mitochondrial respiratory chain complexes I, III, and V activities, were significantly reduced (P<0.05) in the lead-exposed gorup. The typical differential metabolite N-methylisoleucine, identified through serum metabolomics analysis, was negatively correlated with blood lead levels, kidney injury scores, and IL-1β, while positively correlated with catalase (CAT) activity and Ca²⁺-Mg²⁺-ATPase. Conclusions Mitochondrial dysfunction may play a critical role in renal injury induced by bone lead mobilization during late gestation.

The functional realization of proteins and other biological macromolecules depends on conformational dynamics and allosteric regulation, and elucidating their molecular mechanisms is an important foundation for understanding life processes. Molecular dynamics simulations are a powerful tool for investigating conformational evolution at the atomic level. However, traditional methods are limited by simulation timescales and high free-energy barriers, making it difficult to effectively capture rare conformations and their transition pathways. As a result, the development of enhanced sampling techniques has become key to overcoming this bottleneck. As a classical enhanced sampling technique, metadynamics suffers from several shortcomings, including strong dependence on collective variables and significant errors caused by bias potential accumulation. This article reviews three major improvement strategies. The first combines stochastic resetting with metadynamics, using trajectory-resetting mechanisms to improve sampling efficiency while avoiding the difficulty of optimizing collective variables. The second, SinkMeta, employs a “sinking” bias effect to enable efficient exploration of specific regions and paths. The third, OPES-based hybrid methods, improve the stability of free-energy estimation by optimizing the target distribution or the way the bias is constructed. These methods provide new ideas for characterizing free-energy landscapes and studying conformational transitions in complex biological systems, while also promoting the continued development of enhanced sampling methodologies.

Introduction: Beckwith–Wiedemann syndrome (BWS) is a congenital overgrowth disorder associated with dysregulation of genes on chromosome 11p15.5. Infants with BWS can present with hyperinsulinemic hypoglycemia. There are also distinctive clinical features including macrosomia, macroglossia and visceromegaly that may raise suspicion of this diagnosis. Case: A preterm female infant of 30 weeks gestation with a birth weight of 1.87 kg (97th centile) had recurrent hypoglycemia in the neonatal period, requiring escalation to a maximum glucose infusion rate of 17.6 mg/kg/min. Hypoglycemia only resolved after starting intravenous glucagon infusion. Critical sampling during hypoglycemia revealed serum insulin 3.9 µU/mL (3–25 µU/mL), serum ketone 0.2 mmol/L, cortisol 3,053 nmol/L and growth hormone 16.2 ng/mL. These findings supported the diagnosis of non-ketotic hyperinsulinemic hypoglycemia. She was commenced on oral diazoxide with resolution of hypoglycemia and discontinuation of glucagon. Examination at birth revealed macroglossia, hepatomegaly and ballotable kidneys. An initial US abdomen at birth revealed bilateral enlarged kidneys but normal liver. An initial chromosomal study revealed karyotype 46, XX. Over time, additional clinical features became evident fulfilling the diagnostic criteria for BWS, that is, polyhydramnios, large for gestational age, transient hypoglycemia, hyperinsulinism, macroglossia, hemihypertrophy, facial nevi, bilateral ear creases, hepatomegaly and ballotable kidney. A repeat US abdomen surveillance at 4 months old revealed a heterogeneous liver mass with marked vascularity, prompting a diagnosis of hepatic hemangioma. She was commenced on oral propranolol, with reduction in the size and vascularity of the liver hemangioma and decline in alpha-fetoprotein levels. Conclusion The clinical features of BWS may not be recognizable in a preterm baby in early neonatal period. Careful clinical examination should be done in a baby with persistent hyperinsulinemic hypoglycemia for underlying syndromal causes. US surveillance should also be carried out due to increased risk of hepatoblastoma or liver hemangioma in BWS, as was seen in this case.
Infant, Newborn ; Infant ; Beckwith-Wiedemann Syndrome ; Infant, Premature ; Hypoglycemia

Objective: To analyze the epidemiological characteristics, associated factors, and vaccine effectiveness of two pertussis cluster outbreaks in two primary schools in Yangzhong City in 2025, so as to provide evidence for school based epidemic prevention and control. Methods: From August 26 to 30, 2025, a pertussis questionnaire was administered to the epidemic affected classes of two primary schools (school A and school B) in Yangzhong City. A descriptive epidemiological retrospective analysis was used to characterize the pertussis cluster outbreaks in Yangzhong City from March to July 2025. A 1∶5 matched case control study (79 cases, 395 controls) was performed. Multivariate Logistic regression was used to identify associated factors, and the clinical symptom incidence rates, types of pertussis containing vaccines, and timeliness of vaccination were compared between groups using Fisher s exact test. Results: From March to July 2025, a total of 79 pertussis cases were reported in the two schools, with attack rates of 1.33% and 1.01%, respectively. Cases were predominantly aged 7-8 years (85.37% in school A, 73.68% in school B), and the main clinical manifestation was productive cough (63.29%). The pneumonia incidence rate among hospitalized cases ( 57.14 %) was higher than that among nonhospitalized cases(4.17%)(Fisher s exact test, P <0.01). The interval from the last dose to onset was concentrated at 6 to <7 years (44 cases). Logistic regression showed that children exposed to secondhand smoke in daily life ( OR = 3.86 ), those whose desk mates or front/back desk mates took leave due to cough ( OR =4.67), and those whose dining table mates or front/back table mates took leave due to cough ( OR =3.67) had significantly higher risks of pertussis (all P <0.05). A high proportion of both the case group and the control group received the acellular DTaP vaccine (97.47% and 96.96%, respectively),while a low proportion received the pentavalent vaccine (1.27% and 3.04%, respectively). Additionally, one case received only three doses of the acellular DTaP vaccine.The difference in vaccine type distribution between the two groups was not statistically significant (Fisher s exact test, P =0.31). Conclusions The outbreaks represent breakthrough infections under high vaccine coverage. Close contact and secondhand smoke exposure are the main risk factors. A booster immunization strategy with diphtheria-tetanus-pertussis vaccine should be implemented for school aged children.

OBJECTIVE To investigate the characteristics and safety of finerenone use in hospitalized patients with acute heart failure （AHF）.METHODS A single-center retrospective cohort study was conducted， enrolling 171 AHF patients who initiated finerenone therapy during hospitalization at The First Affiliated Hospital of University of Science and Technology of China between November 2023 and April 2026. Baseline characteristics， finerenone use patterns，in-hospital major and minor safety endpoints were collected. Univariate intergroup analysis， univariate and multivariate Logistic regression were performed to identify predictive factors （Firth’s penalized likelihood method was used when events were sparse）. Propensity score matching （PSM） and stabilized inverse probability of treatment weighting （sIPTW） were employed to compare the safety differences between early initiation （≤3 d） and intermediate-to-late initiation （＞3 d） of finerenone. Sensitivity analysis was conducted to verify the robustness of the hyperkalemia-related results.RESULTS A total of 171 hospitalized patients with AHF were included， with 63.7% having heart failure with preserved ejection fraction. The median time to finerenone initiation was 2 d after admission， with early initiation accounting for 64.3%， an initial dose of 10 mg once daily accounting for 83.0%， and concomitant use of sodium-glucose cotransporter 2 inhibitor （SGLT2i） accounting for 83.6%. In the overall cohort， the incidence of hyperkalemia was 3.5%， the incidence of acute kidney injury was 13.5%， and the incidence of the composite endpoint was 21.6%. Concomitant SGLT2i use was associated with a lower risk of hyperkalemia in univariable Logistic regression （OR＝0.18， 95%CI of 0.04-0.86， P ＝0.032） and showed a trend toward a protective association after multivariable Logistic regression adjustment， although this did not reach statistical significance （OR＝0.24， 95%CI of 0.05-1.21， P ＝0.084）； after multivariable Logistic regression adjustment，baseline serum potassium was independently associated with the risk of the composite endpoint （OR＝2.01， 95%CI of 1.06-3.82， P ＝0.032）. Both PSM（OR＝0.70， 95%CI of 0.27-1.83）and sIPTW（OR＝0.70， 95%CI of 0.32-1.52）analyses showed that early initiation of finerenone did not increase the risk of the composite endpoint. Sensitivity analysis results were consistent with the overall cohort analysis.CONCLUSIONS The enrolled patients initiated finerenone early with reasonable starting doses， and a high proportion received concomitant SGLT2i therapy； early initiation did not increase the risk of in-hospital hyperkalemia or acute kidney injury， with an overall favorable safety profile， and concomitant SGLT2i use showed a protective trend with respect to hyperkalemia risk.

Objective: Traumatic brain injury (TBI) patients often experience massive bleeding and require blood transfusion. However, the storage duration of the transfused blood may affect the prognosis of these patients. This study explored the influence of exosomes derived from fresh and aged blood on the prognosis of rats with TBI, so as to provide theoretical support for the blood transfusion management of TBI patients. Methods: Exosomes were isolated from red blood cell (RBC) suspensions stored for 1 week and 5 weeks using ultracentrifugation method. The size, morphology and surface markers of the exosomes were identified by nanoparticle flow cytometry, transmission electron microscopy and Western blotting, respectively. A rat model of TBI was constructed using a mechanical impactor for brain injury. After the successful establishment of the model, exosomes from RBC suspensions stored for 1 week and 5 weeks were injected into the extracellular space of rat brain cells using a stereotactic syringe. Cerebral edema at day 1, 3, 7 and 14 were recorded through cranial magnetic resonance imaging (MRI) scans. Magnetic tracing technology (the tracer was Gd-DTPA solution) was used to evaluate the drug metabolism level in the extracellular space of brain cells of TBI rats. The cranial magnetic resonance imaging was scanned every 15 or 30 minutes, and the recording lasted for a total of 240 minutes. The magnetic images were imported into the 3D-Slicer software in Dicom data format for analysis. Mass spectrometry technology was used to analyze the differential proteins of exosomes from RBC suspensions stored for 1 week and 5 weeks, and functional prediction was carried out to explore the possible mechanisms by which exosomes affect the prognosis of TBI. Results: After injection of exosomes into TBI rats, the areas of cerebral edema on the day 1, 3, 7, and 14 were all significantly higher in the rats treated with exosomes from 5-week-stored RBC suspensions, with peak cerebral edema occurring at day 3. The diffusion volume of the tracer was significantly higher in TBI rats than in normal rats, which implied there was a disorder in the structure of the traumatic brain tissue in TBI rats. Compared with the rats injected with exosomes from 1-week-stored RBC suspensions, those treated with exosomes from 5-week-stored RBC suspensions showed increased tracer diffusion volume within 120 minutes. Mass spectrometry analysis identified 81 differentially expressed proteins between exosomes from RBC suspensions stored for 5 weeks vs 1 week. Among them, 93.83% (76/81) proteins had increased expression levels. The neurodegeneration-related pathways were among the most enriched pathways for upregulated proteins. Conclusion: The exosomes from aged RBC suspensions can lead to exacerbated cerebral edema, disrupted extracellular space, and suppressed metabolic rate in TBI rats, suggesting that transfusion of aged RBC suspensions may have adverse effects on TBI patients.

Background High-sensitivity C-reactive protein (hs-CRP) is a sensitive biomarker for cardiovascular disease (CVD) and can independently predict the risk of cardiovascular events. Although the association between per- and polyfluoroalkyl substances (PFAS) exposure and CVD risk has been widely reported, studies on the association between hs-CRP and PFAS remain limited. Objective To investigate the association between PFAS and hs-CRP levels, to provide a scientific basis for early identification and prevention of environment-related cardiovascular events. Methods This study utilized data from the National Health and Nutrition Examination Survey (NHANES) database (2015–2018). Based on predefined inclusion and exclusion criteria, a total of 3219 participants were included for subsequent analysis. Five PFAS with detection rates exceeding 90% were selected as exposure factors and log-transformed (lnPFAS) for subsequent analysis, including perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorodecanoic acid (PFDA). After selecting potential confounders through a change-in-estimate approach, logistic regression was employed to examine the effects of individual PFAS on serum hs-CRP level. Additionally, quantile g-computation and Bayesian kernel machine regression (BKMR) were applied to assess the combined effects of PFAS mixtures on hs-CRP. Results The study included 3219 participants with a mean age of (50.4±17.6) years, of whom 1554 (48.28%) were male. The median concentrations of the five PFAS compounds were: 1.20 ng·mL⁻¹ (PFHxS), 0.50 ng·mL⁻¹ (PFNA), 1.50 ng·mL⁻¹ (PFOA), 5.20 ng·mL⁻¹ (PFOS), and 0.20 ng·mL⁻¹ (PFDA). The Wilcoxon rank-sum tests revealed statistically significant differences between the elevated serum hs-CRP (≥2 mg·L⁻¹) and normal (<2 mg·L⁻¹) groups for all five PFAS compounds (PFHxS: P=0.005; PFNA: P=0.009; PFOA: P<0.001; PFOS: P<0.001; PFDA: P<0.001). After adjusting for potential confounders, the analysis of individual PFAS exposure demonstrated significant negative associations between serum hs-CRP levels and both ln-PFOS (OR: 0.87; 95%CI: 0.79, 0.96; P=0.0036) and lnPFDA (OR: 0.78; 95%CI: 0.71, 0.86; P < 0.001). The joint effect analysis using quantile g-computation revealed an overall inverse association between PFAS mixtures and hs-CRP, with lnPFDA emerging as a primary contributor; an similar association was observed in males, but not significant in females. Further evaluation through BKMR showed that when PFAS mixture concentrations reached or exceeded P₇₀, their combined effect on hs-CRP became significantly lower than when all PFAS concentrations were at P₅₀, establishing a clear negative dose-response relationship. Conclusion The mixed exposure to PFAS showed a significant negative joint effect on serum hs-CRP levels, with PFDA being the key component contributing to this combined effect. Future prospective cohort studies are warranted to further validate these findings and elucidate the underlying mechanisms involved.

BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*