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.

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.

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.

Aim To investigate the role of triggering receptor expressed on myeloidcells 2(TREM2)in syn-aptic plasticity induced by cocaine addiction.Methods C57BL/6J mice and Trem2 knockout mice were uti-lized in this study to evaluate the alterations in postsyn-aptic density protein 95(PSD-95)and synapsin 1(SYN1)within the cortex and hippocampus of co-caine-addicted mice by using immunological tech-niques.Results HE staining and Nissl staining showed increased neuronal damage in the hippocampus and cortex of mice after cocaine addiction.The results of immunohistochemistry and fluorescence of PSD-95 and SYN1 were consistent with the expression trend of Western blot.In the wild type mouse model,the ex-pression level of PSD-95 in the hippocampus and cortex was lower than that in the saline group,and the ex-pression of SYN1 was higher than that in the saline group.In the knockout mouse model,the expression levels of PSD-95 and SYN1 in the hippocampus and cortex were significantly higher than those in the saline group after cocaine addiction.The expression levels of PSD-95 and SYN1 in the hippocampus and cortex of cocaine knockout mice were higher than those of co-caine wild type mice.Conclusion Cocaine addiction can change the synaptic plasticity,and TREM2 plays a regulatory role in the synaptic plasticity of hippocampus and cortex in mice with cocaine injury.TREM2 is ex-pected to be a new target for studying the mechanism of cocaine addiction.

Objective To investigate the clinical characteristics of severe pertussis in children.Methods Clinical data of 55 children with severe pertussis and admitted to the pediatric intensive care unit(PICU)of Maternal and Child Heath Hospital of Hubei Province from January 2022 to May 2024 were retrospectively analyzed.Patients were grouped according to age(≤3-month group and＞3-month group),vaccination status,and mixed infection status,differences in clinical characteristics among different groups of pediatric patients were compared.Results 55 children with severe pertussis were aged 1 month and 5 days-9 years,all had severe pneumonia,54 children were improved and discharged from hospital,1 died.26 children(47.3％)were aged＜3 months,45 children(81.8％)were unvaccinated,and 47 children(85.5％)had mixed infection.The rates of post-vomiting cough and blood ex-change transfusion in children in ≤3-month group were lower those in＞3-month group(30.8％vs 58.6％;11.5％vs 34.5％,respectively);The rate of elevation of cerebrospinal fluid protein in children in ≤3-month group was higher than that in＞3-month group(61.5％vs 31.0％);The pre-admission disease course of children in ≤3-month group was shorter than that in＞3-month group([10.15±5.64]days vs[14.24±8.90]days),differences were all statistically significant(all P≤0.05).The absolute counts of lymphocyte in the vaccinated group was lower than that in the unvaccinated group([9.92±5.92]× 109/L vs[17.93±11.41]× 109/L,P＜0.05).The usage rate of gamma-globulin in children in the mixed infection group was higher than that in the simple infection group(87.2％vs 50.0％).The length of hospital stay([15.11±6.53]days vs[9.50±4.69]days),length of PICU stay([10.53±5.26]days vs[5.88±4.16]days),and macrolides antibiotic use days([8.36±4.21]days vs[5.00±2.73]days)in children in the mixed infection group were all longer than those in the simple infection group,differences were all statistically significant(all P＜0.05).No independent influencing factors were found to prolong the length of PICU stay in children with severe pertussis.Conclusion Severe pertussis mostly occurs in unvaccinated children aged ≤3 months,with a high incidence of mixed infection,all presenting as severe pneumonia.Vaccination status,mixed infection,and complications are key factors affecting prognosis.

Objective To investigate the clinical characteristics of severe pertussis in children.Methods Clinical data of 55 children with severe pertussis and admitted to the pediatric intensive care unit(PICU)of Maternal and Child Heath Hospital of Hubei Province from January 2022 to May 2024 were retrospectively analyzed.Patients were grouped according to age(≤3-month group and＞3-month group),vaccination status,and mixed infection status,differences in clinical characteristics among different groups of pediatric patients were compared.Results 55 children with severe pertussis were aged 1 month and 5 days-9 years,all had severe pneumonia,54 children were improved and discharged from hospital,1 died.26 children(47.3％)were aged＜3 months,45 children(81.8％)were unvaccinated,and 47 children(85.5％)had mixed infection.The rates of post-vomiting cough and blood ex-change transfusion in children in ≤3-month group were lower those in＞3-month group(30.8％vs 58.6％;11.5％vs 34.5％,respectively);The rate of elevation of cerebrospinal fluid protein in children in ≤3-month group was higher than that in＞3-month group(61.5％vs 31.0％);The pre-admission disease course of children in ≤3-month group was shorter than that in＞3-month group([10.15±5.64]days vs[14.24±8.90]days),differences were all statistically significant(all P≤0.05).The absolute counts of lymphocyte in the vaccinated group was lower than that in the unvaccinated group([9.92±5.92]× 109/L vs[17.93±11.41]× 109/L,P＜0.05).The usage rate of gamma-globulin in children in the mixed infection group was higher than that in the simple infection group(87.2％vs 50.0％).The length of hospital stay([15.11±6.53]days vs[9.50±4.69]days),length of PICU stay([10.53±5.26]days vs[5.88±4.16]days),and macrolides antibiotic use days([8.36±4.21]days vs[5.00±2.73]days)in children in the mixed infection group were all longer than those in the simple infection group,differences were all statistically significant(all P＜0.05).No independent influencing factors were found to prolong the length of PICU stay in children with severe pertussis.Conclusion Severe pertussis mostly occurs in unvaccinated children aged ≤3 months,with a high incidence of mixed infection,all presenting as severe pneumonia.Vaccination status,mixed infection,and complications are key factors affecting prognosis.

Human Respiratory Stem Cells (RSCs) play a crucial role in the maintenance, repair and regeneration of the respiratory system. As a novel therapeutic method, stem cell therapy is a popular research direction in the medical field. And with the in-depth research on the mechanism of pneumonia caused by respiratory infections in recent years, the use of RSCs to explore pneumonia caused by respiratory infections and its therapeutic strategies has become a hot topic. In this paper, we firstly outlined the types of RSCs, summarized the mechanism of pneumonia caused by respiratory tract infections, discussed the advantages of RSCs application and the progress of culture differentiation, and elaborated the therapeutic exploration of RSCs in pneumonia caused by respiratory tract infections.

ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction