Subclinical hypothyroidism (SCH) is a subclinical state of mild hypothyroidism. In recent years, the impact of SCH on multiple systems of the body has gradually attracted attention. Although SCH patients usually do not have obvious clinical symptoms, studies have shown that SCH may be associated with a variety of chronic diseases, such as cardiovascular disease and metabolic syndrome. Due to the complex interrelationship between diabetes mellitus and thyroid disease, researchers have begun to pay attention to the potential impact of SCH on diabetic retinopathy (diabetic retinopathy, DR). This article aims to comprehensively review the current research progress on the impact of SCH on DR, and explore in depth the pathophysiological mechanisms, clinical manifestations, and treatment strategies, providing clinicians with more comprehensive diagnostic and treatment ideas.

ObjectiveBiochemistry and Molecular Biology, a discipline that elucidates life phenomena at the molecular level, serves as a core foundational course in medical education. It provides the theoretical basis for studying other basic and clinical medical subjects, as well as for understanding pathogenesis, disease diagnosis, and treatment. However, its complex content and highly abstract concepts have posed a dual challenge to traditional teaching models: “inefficient instruction” and “inadequate learning outcomes”. Within limited classroom hours, how to engage students and stimulate their intrinsic motivation, and how to help them recognize, understand, and develop a passion for biochemistry from the perspective of the discipline’s essence, have long been key focuses of curriculum research. MethodsUsing the lipid metabolism chapter as an example, this study employs “Rain Classroom”, a generative artificial intelligence (AI)-assisted platform, to support education in four dimensions: teaching, learning, evaluation, and research. In teaching, it assists instructors through virtual experiments, lesson preparation support, knowledge mapping, and assignment design. For learning, it serves as an intelligent study assistant for students, providing automated assignment review, enabling educational resource sharing, and facilitating personalized learning pathways. In evaluation, the platform automates assignment grading, analyzes student performance data, and offers diagnostic feedback and teaching recommendations. In research, it aids educators in collecting and analyzing teaching data, as well as searching for and summarizing relevant literature. ResultsThe results indicate that an educational model integrating teacher-led instruction, student-centered learning, and generative AI assistance significantly enhances teaching quality, students’ self-directed learning abilities, and knowledge mastery. Furthermore, with the support of generative AI, curriculum-based ideological education—focusing on cutting-edge disciplinary advances and topical medical issues—helps cultivate students’ medical spirit of “honoring life and healing the wounded”, thereby fostering the establishment of appropriate professional values. Finally, while generative AI presents both opportunities and challenges for higher education, this study also analyzes potential risks in its teaching applications, emphasizing the need for both instructors and students to avoid over-reliance and to ensure that technological tools consistently serve the fundamental goals of education. ConclusionThis study demonstrates that integrating generative AI, specifically via the “Rain Classroom” platform, can effectively enhance biochemistry education. By supporting teaching, learning, evaluation, and research, this approach improves both educational effectiveness and student outcomes. It also facilitates the incorporation of cutting-edge knowledge and professional ethics, nurturing a patient-centered mindset. Additionally, the study addresses potential implementation risks to ensure that such technological tools remain aligned with the core purpose of education.

Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

Objectives: This study aimed to investigate the clinical characteristics, treatment outcomes, and factors influencing treatment success in patients with denosumab (Dmab)-related osteonecrosis of the jaw (DRONJ). Patients and Methods: This retrospective cohort study included the patients who were diagnosed with DRONJ and treated at the authors’ affiliated hospital, between August 2019 and August 2024. The patients were divided into the three groups; Group 1, low-dose Dmab; Group 2, transition from bisphosphonates (BPs) to low-dose Dmab; Group 3, high-dose Dmab. Differences in clinical characteristics among the groups were compared. Surgical outcomes were classified into three categories: complete healing, partial healing, and no healing. “Treatment success” was defined as the combined proportion of complete and partial healing. Results: A total of 178 DRONJ patients were included in this study. Most of DRONJ occurred in osteoporosis patients. In patients treated with lowdose Dmab, prior BP use resulted in the development of MRONJ within a shorter period after Dmab administration but did not affect disease severity or treatment outcomes. Overall postoperative healing outcomes were favorable at 3 months after DRONJ treatment. The overall treatment success rate was 81.5%; Group 1, 85.0%; Group 2, 82.8%; Group 3, 53.8%, P=0.027). Multiple regression analysis demonstrated that Dmab dosage was a significant factor influencing treatment success, whereas age, treatment duration, lesion location, and DRONJ stage were not (odds ratio, 5.13; 95% confidence interval, 1.19-22.14; P=0.028). Conclusion The earlier onset in the BP to Dmab transition group may be attributable to the cumulative duration of antiresorptive therapy. Patients treated with high-dose Dmab demonstrated poorer prognosis and more frequent recurrence after MRONJ treatment compared with those treated with low-dose Dmab or BP to Dmab transition therapy. herefore, these findings need to be considered for treatment of DRONJ.

ObjectiveTo develop and validate a nomogram based on the albumin-bilirubin （ALBI） score for predicting the risk of severe perioperative complications in patients undergoing hepatectomy for hepatolithiasis. MethodsA retrospective analysis was conducted on the clinical data of 163 hepatolithiasis patients who underwent hepatectomy. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for severe perioperative complications. A nomogram prediction model was constructed and its performance was evaluated. ResultsAmong the 163 patients， 66 and 97 were classified into the low-grade and high-grade ALBI groups， respectively. Significant intergroup differences were observed in gender， total bilirubin， albumin levels， and the incidence of severe complications （P0.05）. Severe complications occurred in 40 patients. Independent risk factors included age 60 years （OR=5.49， P0.001）， high-grade ALBI （OR=8.30， P0.001）， history of biliary surgery （OR=2.60， P=0.035）， hepatectomy （segmentectomy）≥3 （OR=2.75， P=0.028）， and open surgical approach （OR=4.00， P=0.009）. A nomogram for predicting severe perioperative complications was successfully established. Internal validation showed that the model had an area under the ROC curve （AUC） of 0.865， which outperformed traditional single predictors. The calibration curve closely aligned with the ideal curve， with a mean absolute error （MAE） of 0.027. Decision curve analysis （DCA） demonstrated a net clinical benefit when the threshold probability exceeded 10%， superior to that of traditional predictors. ConclusionThe ALBI score-based nomogram is successfully developed and validated to predict the risk of severe perioperative complications in hepatolithiasis patients undergoing hepatectomy. The model demonstrated favorable predictive performance and high clinical utility， serving as an effective tool for both preoperative risk assessment and postoperative risk stratification.

Coronary CT-derived fractional flow reserve (CT-FFR) is a noninvasive alternative to invasive FFR for assessing the hemodynamic significance of coronary artery stenosis. CT-FFR uses routinely acquired coronary CT angiography (CCTA) with artificial intelligence and computational fluid dynamics to estimate pressure gradients, thereby supporting clinical decisionmaking without procedural risk. Adoption and implementation vary widely across regions. In Asia, South Korea exclusively uses HeartMedi+, which enables rapid analysis, streamlined workflow integration, and high user satisfaction. Japan relies primarily on FFR CT, which has national reimbursement and significantly influences treatment strategies, reducing unnecessary invasive procedures. Hong Kong, Singapore, Taiwan, Thailand, and Vietnam remain in early or exploratory phases due to cost, reimbursement, and infrastructure barriers. In the United States, CT-FFR is guideline-endorsed and reimbursed, where HeartFlow is the most widely used, supported by robust clinical validation and outcome data. Despite regional variability, CTFFR offers a noninvasive solution that enhances patient management, reduces unnecessary invasive testing, and is poised for broader clinical integration as technology and validation advance.

Purpose: Medication-related osteonecrosis of the jaw (MRONJ) is a complication of antiresorptive therapy, including bisphosphonates and denosumab. Although bone scintigraphy (BS) detects early metabolic changes, its diagnostic role in MRONJ and its role in assessing systemic skeletal involvement remain unclear. This study analyzed BS tracer uptake patterns and their association with MRONJ severity and clinical variables. Materials and Methods: This retrospective study analyzed 319 patients diagnosed with MRONJ from 2010 to 2019. Three-phase BS, cone-beam computed tomography (CBCT), and clinical data were reviewed. Tracer uptake intensity in the jaw was visually graded, and extra-jaw skeletal uptake was categorized by region and number of involved sites. Associations between the MRONJ stage, jaw uptake intensity, and skeletal uptake beyond the jaw were analyzed. Results: Higher tracer uptake intensity in the jaw was associated with advanced MRONJ stages (P<0.001), particularly Stage 3. However, the number of skeletal sites beyond the jaw did not correlate with the MRONJ stage (P=0.512).Distribution of local and systemic tracer uptake in body patterns across MRONJ Stages did not show statistical significance. Conclusion Elevated tracer uptake in the jaw correlates with advanced MRONJ stages and broader skeletal tracer uptake, suggesting a potential link between local disease severity and systemic skeletal involvement. However, skeletal uptake beyond the jaw does not independently predict the MRONJ stage, suggesting that systemic bone involvement alone may not reflect increased disease severity.

Multidrug-resistant (MDR) bacterial infections have emerged as a serious challenge of global public health crisis. The overuse and misuse of conventional antibiotics have dramatically accelerated the emergence, evolution and worldwide spread of drug-resistant bacterial strains, necessitating urgent exploration of novel antibacterial strategies. Bacteriophages serve as natural bacterial predators offering distinct advantages including high host specificity, autonomous self-replication capabilities and cost-effective large-scale production. However, wild-type phages present significant clinical limitations due to their narrow host ranges, susceptibility to rapid immune clearance and poor penetration of bacterial biofilms, which severely restrict their therapeutic applications. The convergence of synthetic biology, nanotechnology and advanced gene editing technologies has accelerated the development of engineered bacteriophage platforms, providing programmable, scalable and clinically translatable pathways to overcome these inherent biological constraints. Here, we systematically delineate four fundamental strategies for engineered bacteriophage development. Chemical modification utilizes reactive functional groups such as amino, carboxyl and thiol moieties on capsid proteins through esterification, amidation or click chemistry reactions to achieve precise drug conjugation and surface functionalization. In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As an intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.

Objective In order to understand the current resistance status of Aedes albopictus(Ae. albopictus) adult population to commonly used insecticides and the resistance dynamics development in Zhejiang Province and provide a theoretical basis for the scientific and rational use of hygienic insecticides. Methods Resistance determination was carried out using the diagnostic dose method(GB/T 26347-2010)recommended by WHO in the adult mosquito contact cylinder method to monitor the resistance of Ae. albopictus field populations in 11 cities and districts in Zhejiang Province in 2024. Results The monitoring result showed that adult Ae. albopictus in 11 areas were resistant or suspected resistant populations to both cis-cypermethrin and permethrin; suspected and resistant populations to the organophosphate insecticide malathion were as high as 81.82%; while suspected resistance to the carbamate insecticide residual carbofuran accounted for 45.45%, and the rest of the monitoring sites were sensitive to it. Conclusions The result suggest that the generalized resistance of Ae. albopictus populations to pyrethroids and organophosphorus insecticides in the field in Zhejiang Province needs to be highly emphasized. In future mosquito vector and mosquito-borne disease control, insecticides should be selected based on the resistance monitoring information, while following scientific guidelines for insecticide use.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.