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.

Objective: To investigate the prevalence of depressive symptoms and their associated factors among students in Zhejiang Province, so as to provide evidence for targeted prevention strategies. Methods: A stratified cluster random sampling method was used to select 23 829 college students and primary and secondary school students aged 11-22 years in Zhejiang Province from December 2019 to February 2020. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Three machine learning algorithms, including Logistic regression, random forest, and eXtreme Gradient Boosting (XGBoost), were applied to construct predictive models, and key associated factors were identified by comparing model performance. Results: The detection rate of depressive symptoms among students in Zhejiang Province was 19.92%; the rates were 17.20% in boys and 22.87% in girls( χ 2=164.89, P <0.05). The CES-D total score was 9.00(4.00,13.00). Multiple Logistic regression analysis revealed that loneliness had the strongest association with depressive symptoms ( AOR =9.58, 95% CI =8.90-10.30), while bullying exposure ( AOR =4.39, 95% CI =4.02-4.80), female students( AOR =1.81, 95% CI =1.68-1.94)，never eating breakfast ( AOR = 2.34，95% CI =2.00-2.67) and overweight/obesity( AOR =1.10，95% CI =1.08-1.12) were significant associated factors of depressive symptoms among students (all P <0.05). Analysis based on the XGBoost model produced highly consistent results, identifying the above 5 factors as the core features with the highest correlation strength (all P <0.05). Conclusions Female, loneliness, bullying exposure, frequency of weekly breakfast and BMI are strongly associated with depressive symptoms among students. Mental health education for high risk groups should be strengthened, and coordinated prevention efforts between families and schools are recommended.

Renal Fanconi syndrome (FS) is a rare renal manifestation of primary Sjögren's syndrome (pSS). This study aims to analyze the clinical and prognostic characteristics of patients with pSS-associated renal FS (pSS-FS) and provide insights for clinical management.

ObjectiveTo explore the clinical efficacy and mechanism of Bupi Qingfei prescription （BPQF） in treating stable bronchiectasis in the patients with syndromes of lung-spleen Qi deficiency and phlegm-heat accumulation in the lungs. MethodsA randomized， double-blind， placebo-controlled trial was conducted. Patients were randomized into BPQF and placebo control （PC） groups. On the basis of conventional Western medicine treatment， the BPQF granules and placebo were respectively administered at 10 g each time， twice a day， for a course of 24 weeks. The TCM symptom scores， Quality of Life Questionnaire for Bronchiectasis （QOL-B） scores， lung function indicators， T lymphocyte subsets， level of inflammatory factors in the sputum， level of neutrophil elastase （NE） in the sputum， and occurrence of adverse reactions were observed before and after treatment in the two groups. ResultsA total of 64 patients completed the study， encompassing 32 in the BPQF group and 32 in the PC group. After treatment， the BPQF group showed decreased TCM symptom scores （P<0.01）， increased QOL-B scores （P<0.01）， and declined levels of tumor necrosis factor （TNF）-α and NE （P<0.05， P<0.01）. The PC group showed decreased TCM symptom （except spleen deficiency） scores （P<0.01）， increased the QOL-B health cognition and respiratory symptom domain scores （P<0.05， P<0.01）， and a declined TNF-α level （P<0.01）. Moreover， the BPQF group had lower TCM symptom （except chest tightness） scores （P<0.05， P<0.01）， higher QOL-B （except treatment burden） scores （P<0.05， P<0.01）， and lower levels of interleukin-6 and TNF-α （P<0.05） than the PC group. Neither group showed serious adverse reactions during the treatment process. ConclusionBPQF can ameliorate the clinical symptoms of stable bronchiectasis patients who have lung-spleen Qi deficiency or phlegm-heat accumulation in the lungs by regulating the immune balance and inhibiting airway inflammatory responses.

Objective To investigate the predictive value of Mayo adhesion probability(MAP)score for intraoperative bleeding during microchannel percutaneous nephrolithotomy(PCNL), so as to provide reference for optimizing surgical decisions.Methods A retrospective analysis was conducted on the clinical data of 86 patients who underwent microchannel PCNL at our hospital during Jan.2018 and Jul. 2025.Patients were divided into two groups based on preoperative CT-derived MAP scores:MAP score＜3 group(n=45)and MAP score≥3 group(n=41).Baseline characteristics, surgical parameters and outcome measures were compared between the two groups.Univariate and multivariate logistic regression analyses were performed to identify risk factors for intraoperative bleeding(defined as a postoperative hemoglobin decrease of ≥20 g/L). Results The incidence of intraoperative bleeding was significantly higher in the MAP score≥3 group than in the MAP score＜3 group(43.9% vs.20.0%, P=0.017).Multivariate analysis identified MAP score ≥3(OR=3.045, 95%CI:1.125-9.547, P=0.019), use of anticoagulant medication(OR=3.016, 95%CI:1.251-9.257, P=0.020), establishment of multiple tracts(OR=5.445, 95%CI:1.798-17.578, P=0.003), and operation time ≥90 minutes(OR=5.697, 95%CI:1.890-13.632, P=0.001)as risk factors for intraoperative bleeding.The area under the curve for the MAP score in predicting intraoperative bleeding was 0.704.Conclusion The MAP score is an independent risk factor for intraoperative bleeding during microchannel PCNL.Preoperative assessment can help identify high-risk patients and provide a basis for optimizing surgical decision-making.

Objective To investigate the clinical efficacy of minimally invasive mitral valvuloplasty (MVP) in the treatment of infective endocarditis (IE) with mitral regurgitation (MR). Methods A retrospective analysis was conducted on the clinical data of patients who underwent MVP for IE with MR at the Department of Cardiovascular Surgery in Zhongshan Hospital, Fudan University from 2016 to 2020. Patients were divided into two groups based on the surgical incision: those with a right mini-thoracotomy were classified as a minimally invasive surgery (MIS) group, and those with a median sternotomy (MS) were classified as an MS group. All patients had isolated mitral valve involvement. Perioperative data were analyzed, and mid- to long-term outcomes were compared between the two groups. Results A total of 86 patients were included, with 40 in the MIS group [22 males and 18 females, with a mean age of (39.78±15.36) years ranging from 14 to 75 years] and 46 in the MS group [27 males and 19 females, with a mean age of (49.94±16.13) years ranging from 14 to 71 years]. The patients in the MIS group were relatively younger (P=0.004) with better preoperative cardiac function (P=0.004). There was no statistical difference in preoperative fever, gender, or comorbidities between the two groups (P>0.05). The MIS group had shorter postoperative ventilation times, less postoperative 24-hour drainage, less blood transfusion, and shorter total hospital stays compared to the MS group (P＜0.05). There was no statistical difference in cardiopulmonary bypass times or ICU stays between the two groups (P>0.05). The perioperative complication rates and mortality rates were not significantly different between the two groups (P>0.05). Follow-up was conducted for 11-92 months, with a mean duration of (49±19) months and an overall follow-up rate of 91.9%. During the follow-up, 3 patients in each group required reoperation for mitral valve issues, with no statistical difference in incidence (7.5% vs. 6.5%, P=0.691). There were no warfarin-related complications, recurrences, or deaths in either group during follow-up. Multivariate regression analysis identified age, preoperative cardiac function, and surgeon experience as influencing factors for the choice of surgical approach. Conclusion Minimally invasive MVP for IE with MR is relatively safe in the perioperative period and shows significant efficacy, with clear mid- to long-term outcomes. It is recommended for younger patients with better preoperative cardiac function and when performed by surgeons with extensive experience in mitral valvuloplasty.

In recent years， repetitive transcranial magnetic stimulation （rTMS） has garnered significant attention as a therapeutic approach for sleep disorders in the elderly. However， the prevailing rTMS protocols are predominantly developed based on normative neurophysiological data derived from young adults and fail to incorporate individualized parameters tailored to the brain characteristics of the elderly. To address this gap， the consensus development group synthesized the latest evidence from 2010 to 2025 and established a standardized rTMS protocol specifically for elderly patients with sleep disorders. Adhering to the Appraisal of Guidelines for Research and Evaluation II （AGREE II） framework， systematically screened randomized controlled trials （RCTs） and systematic reviews regarding rTMS in the treatment of sleep disorders across various conditions. Meanwhile， the Grading of Recommendations Assessment， Development and Evaluation （GRADE） system was employed to rigorously grade the quality of evidence and the strength of recommendations. This consensus guideline delineates precise rTMS protocols for the management of sleep disorders in the elderly， highlights the adjustment of stimulation intensity according to scalp-cortex distance recommends either MRI‑guided neuronavigation or the Beam F3/F4 heuristic approach for accurate target localization， thereby providing precise rTMS intervention protocol for sleep disorders in the elderly， aiming to enhance clinical efficacy while ensuring treatment safety. ［Funded by National Key Research and Development Program （number， 2023YFC3603200）； General Program of Shenzhen Science and Technology Innovation Commission （number， JCYJ20240813112859008， JCYJ20240813112900002）； Youth Program of Shenzhen Kangning Hospital （number， KN2023A004）； www.guidelines-registry.cn number， PREPARE-2026CN530］

Owing to its inherent advantages—such as being non-destructive, rapid, highly molecule-specific, and minimally interfered with by moisture—Raman spectroscopy has been widely adopted in the fields of skin barrier function assessment, monitoring the transdermal penetration of active cosmetic ingredients, and the identification and quality control of cosmetic products. Despite these strengths, the practical application of this technique faces a significant bottleneck: the strong fluorescence background generated by endogenous skin components and exogenous cosmetic additives. Endogenous skin substances, such as structural proteins (e.g., collagen and elastin), metabolic coenzymes (e.g., nicotinamide adenine dinucleotide), and pigments (e.g., melanin), together with exogenous cosmetic constituents like organic colorants, chemical sunscreens, and fragrances, often possess strong absorption and emission characteristics. When excited by lasers, these components produce a fluorescence background that can be 10⁶ to 10⁸ times stronger than the Raman scattering signals, effectively masking the inherently weak vibrational fingerprint information. In recent years, driven by the rapid development of optoelectronic hardware and artificial intelligence algorithms, fluorescence suppression strategies have evolved from isolated, single-method approaches into comprehensive, multi-level synergistic systems. These systems are categorized into three distinct tiers: sample preparation, signal acquisition, and data processing. At the sample preparation level, techniques such as photobleaching and surface-enhanced Raman spectroscopy (SERS) are employed to eliminate or bypass the generation of fluorescence at the source. At the signal acquisition level, instrumental improvements—including the use of long-wavelength near-infrared excitation (typically 785 nm or 1 064 nm), confocal spatial filtering, and shifted excitation Raman difference spectroscopy (SERDS)— are utilized to physically isolate Raman signals from the fluorescence background. Furthermore, at the data processing level, numerical baseline correction methods such as polynomial fitting, penalized least squares (e.g., airPLS, arPLS), wavelet transform, and derivative algorithms are increasingly integrated into the analytical pipeline to extract Raman spectral features from mixed signals without increasing hardware costs or acquisition time. This review provides a systematic categorization and critical evaluation of these fluorescence suppression methods, detailing their underlying principles, technical advantages, and inherent limitations in diverse experimental setups. By focusing on critical application scenarios—including skin barrier assessment, percutaneous absorption monitoring, the routine quality control of cosmetics, and the emerging field of portable on-site detection—this paper explores the current state of technique selection and optimization. Finally, the article discusses future development trends, emphasizing the necessity of constructing adaptive, tiered suppression strategies, developing intelligent and automated data processing algorithms, and promoting the integration of portable, multi-modal diagnostic devices. The objective of this review is to provide a comprehensive technical reference to facilitate the transition of Raman spectroscopy from a specialized laboratory tool into a routine, robust analytical platform for advancements in skin science and cosmetic research.

Objective: To analyze the characteristics and key risk factors of abnormal blood disposal throughout the 2024-2025 blood collection and supply process based on nationwide multi-site monitoring data, develop a comprehensive prevention and control strategy across the entire chain, reduce preventable blood waste, and ensure clinical blood safety. Methods: According to the Guidelines for Haemovigilance (T/CSBT 001-2026), we extracted 74 cases of abnormal blood disposal events reported by the China Blood Transfusion Association′s Blood Safety Monitoring System from January 1 2024, to December 31 2025, and conducted descriptive statistical analysis on the distribution of events, types of deviations, root causes, and classifications of disposal manifestations. Results: A total of 664 adverse events related to blood collection and supply were reported over two years, with 74 cases involving discarded abnormal blood units, accounting for 11.1% of the total. Among these, blood component preparation (40.5%) and blood collection (37.8%) remained traditional high-risk stages. The proportion of blood waste occurring during storage, distribution, and transportation increased from 7.7% in 2024 to 34.3% in 2025. Deviations from standard operating procedures (SOP) by personnel were the primary cause, accounting for 74.3% of cases. Discarded blood units were categorized into four types: compromised closed blood bag systems (40 cases), mainly due to inadequate heat sealing, physical damage, or dropped bags; blood out of the cold chain (12 cases), primarily resulting from blood being left at work sites; imbalanced proportion of preservation solution (10 cases), mostly caused by blood collection volumes exceeding the standard capacity of blood bags; and other causes (12 cases). Conclusion: Human operational errors are the core cause of abnormal blood waste. The collection and preparation stages have long been at high-risk, and the risks in the storage and transportation stages have been increasing year by year. We should focus on standardizing personnel management, improving specialized operation norms such as heat sealing, transportation, and storage, establishing a full-process intelligent cold chain monitoring and multi-node visual verification mechanism, and systematically reducing the occurrence rate of abnormal blood waste through a closed-loop quality intervention system, thereby improving the utilization efficiency of voluntary blood donation resources.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.