Biomolecules & biomedicine最新文献

Although concurrent chemoradiotherapy (CCRT) has improved outcomes in locally advanced head and neck cancer (LA-HNC), radiation-induced periodontitis (RIP) remains an under-recognized oral toxicity with significant consequences, including tooth loss and osteoradionecrosis. This study evaluates the utility of the novel CARWL score-a combined index of the C-reactive protein-to-albumin ratio (CAR) and significant weight loss (SWL)-for stratifying the risk of RIP in LA-HNC patients without baseline periodontitis undergoing CCRT. We conducted a retrospective analysis of 67 LA-HNC patients who underwent CCRT and received detailed oral examinations before and after treatment; none had periodontitis at the initiation of CCRT. Receiver operating characteristic (ROC) curve analysis identified an optimal pretreatment CAR cutoff of 3.07, with SWL defined as greater than 5% body weight loss in the preceding six months. Based on CAR (≥3.07 vs. <3.07) and SWL (present vs. absent), patients were categorized into three CARWL groups. The primary endpoint was the association between the baseline CARWL group and the rates of RIP following CCRT. RIP was diagnosed in 17 patients (25.4%) during follow-up, with incidences increasing progressively across CARWL-0, CARWL-1, and CARWL-2 groups (11.8% vs. 20.8% vs. 38.5%; p = 0.007). In multivariable Cox proportional-hazards analysis, a higher CARWL score emerged as an independent predictor of increased RIP risk (adjusted HR = 3.64; 95% CI 1.41-9.37; p = 0.007), and supplementary logistic regression sensitivity analysis corroborated these findings (adjusted OR = 3.58; 95% CI 1.35-9.45). These findings demonstrate that the pretreatment CARWL score serves as a straightforward and readily available biomarker that effectively stratifies the risk of radiation-induced periodontitis in LA-HNC patients treated with CCRT.

Chronic otitis media with effusion (COME) is a prevalent condition that poses significant risks to the growth and development of children with adenoidal hypertrophy (AH). This study investigates the risk factors associated with COME in children diagnosed with AH and establishes a clinical prediction nomogram to enhance diagnostic accuracy. The study included 311 children with AH, diagnosed through lateral nasopharyngeal radiographs, from the Department of Otorhinolaryngology Head and Neck Surgery at the First Affiliated Hospital of Anhui Medical University. Risk factors were identified using the least absolute shrinkage and selection operator (LASSO), while Firth's penalized logistic regression analysis was employed to further refine the variables and develop a predictive model. The model's performance was assessed using the C-index, calibration curve, and decision curve analysis, with internal validation conducted through bootstrapping. The resulting predictive nomogram included four key risk factors: young age, vitamin D3 deficiency, degree of AH, and tympanometry results. The model exhibited strong predictive capabilities, achieving a C-index of 0.945 (95% confidence interval: 0.941, 0.949). Bootstrapping validation confirmed a high C-index of 0.934. The calibration curve demonstrated good alignment, while the decision curve indicated a net benefit across thresholds of 10%-90%. This nomogram-incorporating tympanometry, AH degree, serum vitamin D3 levels, and age-serves as a valuable tool for clinicians and families in assessing the risk of COME in children with AH.

Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication that poses significant risks to both mothers and their offspring, with genetic susceptibility believed to play a role in its pathogenesis. This study examined the association between the Pro12Ala (Pro [C]→Ala [G]) polymorphism in the peroxisome proliferator-activated receptor γ2 (PPARγ2) gene and the risk of developing GDM. A systematic literature search was conducted across databases including PubMed/Medline, Web of Science, Embase, and the Cochrane Library, identifying clinical studies that evaluated the relationship between the PPARγ2 Pro12Ala variant and GDM. Strict inclusion criteria ensured that all case groups comprised exclusively women diagnosed with GDM. Data on study characteristics, sample sizes, and allele frequencies were extracted, and meta-analyses were performed using RevMan 5.3 and Stata with Hartung-Knapp random-effects models. Fifteen studies were included in the analysis. The Pro12Ala polymorphism showed no significant association with GDM risk across allelic (Ala [G] vs. Pro [C]), dominant (CG+GG vs. CC), and recessive (GG vs. CG+CC) models (allelic: OR=0.90, 95% CI=0.75-1.08, p=0.26; dominant: OR=0.92, 95% CI=0.74-1.13, p=0.42; recessive: OR=0.82, 95% CI=0.54-1.25, p=0.33; all p>0.05). Subgroup analyses by ethnicity indicated a potential protective association of the Ala (G) allele with GDM in East Asian populations, while no significant associations were found in European or Middle Eastern populations; ethnicity was identified as a significant effect modifier (p<0.05). There were no meaningful differences in subgroups categorized by study quality and sample size. Sensitivity analyses confirmed the robustness of the findings, and small-study effects detected by Egger's test did not substantially alter the pooled estimates. In conclusion, the PPARγ2 Pro12Ala polymorphism was not significantly associated with GDM risk in the general population. The potentially protective trend observed in East Asian women warrants cautious interpretation due to concerns regarding multiple testing, allele-frequency variation, and limited statistical power.

Dantrolene is the definitive treatment for malignant hyperthermia (MH), a rare and life-threatening disorder. This retrospective study aimed to achieve two objectives: (1) to characterize the indications and frequency of dantrolene administration in both medical and surgical settings, and (2) to evaluate whether perioperative dantrolene may serve as a surrogate marker for identifying MH cases. Using pharmacy records, we identified hospitalized patients who received dantrolene between 2010 and 2024. Each recipient underwent a chart review to examine the clinical context of dantrolene administration. A total of 1,199,450 inpatient pharmacy records were reviewed, revealing 118 patients who received dantrolene, resulting in an incidence rate of 1 in 10,165 hospital admissions (95% CI: 1 in 8,488 to 1 in 12,280). Among these, 87 patients (74%) received oral dantrolene: 84 for chronic spasticity, two for neuroleptic malignant syndrome, and one as preoperative prophylaxis due to a history of MH. The remaining 31 patients (26%) received intravenous dantrolene. Seventeen patients received perioperative dantrolene for suspected MH; of these, nine cases (53%) were subsequently clinically confirmed as MH. Based on these findings and the total number of surgical procedures involving general anesthesia (n=885,127), the estimated prevalence of MH following general anesthesia was calculated to be 1 in 98,328 exposures (95% CI: 1 in 51,813 to 1 in 215,054). Dantrolene was administered at an approximate rate of 1 per 10,000 hospital admissions, primarily in oral formulation for chronic spasticity. Among the patients who received perioperative dantrolene, approximately half were confirmed to have MH, resulting in an estimated MH prevalence of 1 in 100,000 patients exposed to general anesthesia.

Massive hemoptysis is a life-threatening complication in patients with advanced primary lung cancer, and effective, safe treatments are crucial. This study aimed to investigate the efficacy and safety of CalliSpheres drug-eluting bead bronchial arterial infusion chemoembolization (DEB-BACE) for managing this condition. A retrospective analysis included 144 patients with advanced primary lung cancer and massive hemoptysis treated at multiple hospitals from January 2019 to January 2023. Patients undergoing bronchial artery embolization were divided into two groups: the observation group (n=76) received CalliSpheres DEB-BACE with epirubicin, and the control group (n=68) received 8spheres blank embolization. Both groups achieved successful hemostasis, with no statistically significant difference in success rates (observation group: 88.16%, control group: 86.76%). However, the observation group had a significantly longer median duration without hemoptysis (96 days vs. 50 days). Two months post-therapy, the observation group showed higher objective response rates (82.89% vs. 38.24%) and disease control rates (92.11% vs. 66.18%) compared to the control group. Adverse reactions were manageable and similar between groups, with no serious complications observed. By January 31, 2024, the observation group had significantly longer median overall survival (11 months vs. 7 months). The DEB-BACE treatment demonstrates safety and efficacy in managing massive hemoptysis in patients with advanced lung cancer. However, the superiority of this approach over bland embolization remains to be established through well-designed prospective studies. Future research is anticipated to provide a definitive comparison and further validate the role of DEB-BACE in clinical practice.

Rare liver diseases (RLDs) are diverse and often misdiagnosed conditions that impose significant clinical and public health challenges due to their variable presentations and limited treatment options. This study aims to synthesize contemporary evidence on the etiology, classification, diagnostics, and management of RLDs and to identify near-term research and implementation priorities. We conducted a systematic search of PubMed and Scopus for the years 2015 to 2025 using predefined keywords. We included peer-reviewed human studies, such as guidelines, randomized trials, and large registries, focusing on mechanisms, diagnostic strategies, and treatments. We excluded animal studies and non-peer-reviewed reports, extracting data on disease biology, diagnostic tools, outcomes, and molecular therapies. RLDs can be categorized into genetic/inherited, autoimmune cholestatic, and other vascular/metabolic entities. Care for these diseases is increasingly guided by structured pathways that integrate biochemistry and serology with magnetic resonance cholangiopancreatography (MRCP), elastography, targeted next-generation sequencing (NGS), and selective biopsy. Emerging biomarkers, such as circulating microRNAs, alongside machine learning in imaging techniques, enhance disease staging and prognostication. Key management strategies include the use of bile-acid modulators, surgical interventions, and ileal bile acid transporter (IBAT) inhibitors for progressive familial intrahepatic cholestasis (PFIC). Lifelong copper chelation is recommended for Wilson disease, with trientine preferred for neurologic phenotypes. Supportive care in alpha-1 antitrypsin deficiency (A1ATD) is complemented by the investigation of molecular chaperones. Additionally, gene-directed therapies, gene editing, RNA-based approaches, and cell therapies show early promise but raise concerns regarding durability, safety, and ethical considerations, particularly for pediatric patients. In conclusion, implementing precision medicine frameworks that rely on standardized diagnostics, multicenter registries, and equitable access is crucial for facilitating earlier detection and translating mechanism-targeted therapies into sustainable, globally accessible benefits.

Bariatric metabolic surgery (BMS) is a common intervention for severe obesity, yet its effects on cancer risk remain unclear. Observational studies and meta-analyses yield inconsistent findings, while randomized controlled trials often lack adequate follow-up to evaluate cancer outcomes. This study aims to emulate a target trial using observational data, employing a transparent and robust methodology to address this issue. We constructed a large retrospective cohort of adults with obesity in Qatar using electronic medical records from the public health system, with data available from 2018. We developed and applied iterative time distribution matching (ITDM) which is an iterative version of prescription time distribution matching (PTDM) as an improved approach to mitigate immortal time bias. This adaptation facilitated the alignment of time-zero (T0) between BMS recipients and non-recipients. Subsequently, we applied a Cox proportional hazards regression model, controlling for confounders and prognostic covariates, for data analysis. The final study cohort comprised 124,780 individuals aged 30 years and older, including 1,465 who underwent BMS and 1,583 who developed cancer during the follow-up period. The median follow-up duration was 7.79 years (IQR: 4.89-10.85). In the confounder- and prognostic covariate-adjusted Cox model, BMS was associated with a reduced hazard of cancer (HR 0.49, 95% CI 0.31 to 0.76). Given potential residual confounding and the limited outcome data, these findings provide preliminary evidence of a protective association and should be interpreted cautiously. This approach emphasizes transparency in trial emulation design, and future studies should focus on specific cancer types and long-term outcomes as additional data become available.

Childhood-onset type 1 diabetes (T1D) is a chronic autoimmune disease characterized by a steadily increasing global incidence and significant public health implications. The relationship between maternal smoking during pregnancy and T1D risk remains uncertain. To clarify this association, we conducted a meta-analysis of prospective cohort studies to enhance methodological reliability. We systematically searched PubMed, Embase, and Web of Science from their inception to May 2025 for prospective cohort studies examining the link between maternal smoking during pregnancy and the incidence of T1D in offspring. Risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model, accounting for heterogeneity. Twelve prospective cohort datasets from ten studies, encompassing over 5.9 million children, were included. Maternal smoking during pregnancy was significantly associated with a reduced risk of childhood-onset T1D (RR: 0.74, 95% CI: 0.72-0.76, p < 0.001), with no evidence of statistical heterogeneity (I² = 0%, p = 0.48). This association remained robust across sensitivity analyses that excluded one dataset at a time. Subgroup analyses demonstrated consistent results across various categories, including cohort size, prevalence of maternal smoking, method of T1D diagnosis, and adjustments for maternal age, diabetes, and delivery mode. Notably, the inverse association was significantly weaker in studies that did not adjust for maternal diabetes (RR: 0.79 vs. 0.72, p for subgroup difference = 0.01). We found no substantial evidence of publication bias (Egger's test, p = 0.55). In conclusion, this meta-analysis identified an inverse association between maternal smoking during pregnancy and the incidence of childhood-onset T1D. However, this finding should be interpreted cautiously, as residual confounding cannot be ruled out, and maternal smoking is associated with numerous serious adverse health consequences.

Masseter muscle spasm after succinylcholine can herald malignant hyperthermia (MH) in genetically susceptible individuals. We aimed to describe the perioperative course and genetic findings in a patient who developed transient masseter spasm and postoperative rhabdomyolysis after general anesthesia. This single-patient case report draws on perioperative observations, laboratory testing, and whole-genome sequencing. Immediately after induction with propofol and succinylcholine, the patient experienced transient masseter spasm; anesthesia was then maintained with total intravenous anesthesia (propofol and remifentanil). Postoperatively, laboratory studies showed severe rhabdomyolysis with mild pigment nephropathy; the patient received intravenous hydration, laboratory values normalized by postoperative day 4, and discharge occurred in good condition. Whole-genome sequencing identified heterozygous ryanodine receptor 1 (RYR1) c.1840C>T (p.Arg614Cys)-a known MH-susceptibility variant in the skeletal-muscle ryanodine receptor-and butyrylcholinesterase (BCHE) c.293A>G (p.Asp98Gly), which reduces butyrylcholinesterase activity and delays succinylcholine hydrolysis. The coexistence of these variants likely synergistically increased sarcoplasmic reticulum Ca²⁺ release and prolonged succinylcholine effect, precipitating rhabdomyolysis; to our knowledge, this appears to be the first reported case linking concurrent RYR1 and BCHE variants to rhabdomyolysis following general anesthesia.

Sentinel lymph node biopsy (SLNB) is a pivotal technique employed to assess the necessity for axillary lymph node dissection (ALND), evaluated during the preoperative phase through clinical and radiological findings. The preoperative identification of sentinel lymph node metastasis has gained paramount importance in the surgical management of breast cancer. Tumor budding (TB) has emerged as a significant prognostic marker across various cancers, including breast cancer, where it is instrumental in detecting lymph node metastasis. This study aims to investigate the role of tumor budding in predicting sentinel lymph node metastasis in preoperative breast biopsies. We included patients diagnosed with breast cancer, specifically those with invasive ductal carcinoma (IDC), who underwent preoperative needle biopsy and subsequent evaluation of postoperative surgical specimens, as well as SLNB at our medical center. The histological slides of these cases were reevaluated, and tumor cell clusters comprising up to four cells were classified as TB. Lymph nodes exhibiting tumor cell involvement, limited to macrometastasis, were classified as positive. A total of 65 patients were enrolled in the study. Among these, 36 patients exhibited TB in their preoperative biopsies, while 29 did not. The median tumor sizes were 20 mm (range: 6-50 mm) in the TB-positive group and 19 mm (range: 2-50 mm) in the TB-negative group (p=0.3). Sentinel lymph node metastasis was detected in 18 patients with TB, compared to only five patients without TB, a difference that was statistically significant (p=0.006). We conclude that evaluating tumor budding in breast tru-cut specimens, in conjunction with clinical and radiological findings, may enhance the preoperative assessment of breast cancer cases requiring SLNB.