ObjectiveTo explore the correlation between the occurrence of cardiovascular events in rheumatoid arthritis（RA） and traditional Chinese medicine（TCM） syndrome. MethodsThe cross-sectional study selected 6713 RA patients from 122 centres nationwide， in which general information such as name， gender， age， height， body weight， and course of disease were collected by completing a questionnaire； patients were classified into eight types of syndrome according to the information of their four examinations，i.e. wind-dampness obstruction syndrome， cold-dampness obstruction syndrome， dampness-heat obstruction syndrome， phlegm-stasis obstruction syndrome， stasis-blood obstructing collateral syndrome， qi-blood deficiency syndrome， liver-kidney insufficiency syndrome， and qi-yin deficiency syndrome. According to the occurrence of cardiovascular events， they were divided into the occurrence group and the non-occurrence group， and the condition assessment data and laboratory examination indexes were recorded. The test of difference between groups was used to analyse the possible risk factors for the occurrence of RA cardiovascular events， and binary logistic regression was used to analyse the correlation between TCM syndromes and RA cardiovascular events. ResultsA total of 6713 RA patients were included， including 256 cases in occurrence group and 6457 in non-occurrence group. There was no statistically significant difference between groups in terms of height， gender， insomnia， appetite， white blood cell（WBC）， hemoglobin（HGB）， platelets（PLT）， rheumatoid factor（RF）， anti-cyclic peptide containing citrulline（CCP）， alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， γ-glutamyl transpeptidase（GGT）， urea creatinine（CREA）， and glucose（GLU）（P＞0.05）. The TCM syndromes between groups showed significant statistic differences（P＜0.05）. Patients in occurrence group had longer disease duration， heavier body weight， and older age； more severe conditions such as disease activity（DAS-28）， number of painful joints（TJC）， number of swollen joints（SJC）， health questionnaire scores（HAQ）， visual analog scores（VAS）， restlessness， and fatigue； higher blood sedimentation rate（ESR）， low-density lipoprotein（LDL-C）， triglyceride（TG）， total cholesterol（TC）， D-Dimer， and lower high-density lipoprotein（HDL-C）（P＜0.05）. The distribution of syndrome types showed that dampness-heat obstruction syndrome accounted for the largest proportion of patients in both groups and was higher in RA cardiovascular events. Logistic regression analysis showed that the occurrence of RA cardiovascular events was strongly associated with dampness-heat obstruction syndrome［OR=5.937， 95%CI （4.434， 7.949）， P＜0.001］. ConclusionThe occurrence of RA cardiovascular events were associated with TCM syndromes， and the probability of cardiovascular events in the RA patients with dampness-heat obstruction syndrome was 5.937 times higher than patients with other TCM syndromes.

An ideal dermal filler should integrate filling, repair, and anti-aging effects, with immediate tissue augmentation, slow degradation, and progressive stimulation of collagen regeneration. However, commonly used hyaluronic acid (HA) hydrogels, while effective for rapid filling, suffer from limited duration of support, weak cell adhesion, and an inability to promote collagen regeneration. Silk fibroin (SF), a natural protein from silkworm cocoons, is known for its excellent cell adhesion and collagen-stimulating abilities. However, its limited gelation capability restricts its potential application as a standalone injectable hydrogel. Based on a complementary strategy, this study combines the rapid gelling properties of HA with the collagen regenerative properties of SF to create a co-crosslinked HA-SF hydrogel. The composite hydrogel merges HA's rapid filling effect with SF's strong tissue adhesion and collagen-stimulating abilities. The formulation, physicochemical properties, degradation, biocompatibility, and filling effects of the HA-SF hydrogel were systematically investigated. HA-SF hydrogel exhibits excellent mechanical properties and ensures long-term support while maintaining injectability. Interestingly, after intradermal injection in the UVB-induced photoaging model, HA-SF hydrogel not only enhances hydrogel-cell interaction but also continues to stimulate collagen regeneration, especially type III collagen. This dual action achieves the biological effects of repair and anti-aging while maintaining the filling effect. Proteomic analysis confirms that repair and anti-aging effects are enhanced by the regulation of skin fibroblasts and modulation of amino acid and lipid metabolism. This composite hydrogel holds strong promise for clinical applications, offering a safer, long-lasting, and more natural injectable filler that combines filling, repair, and anti-aging into one system.

Proteolysis-targeting chimeras (PROTACs) have emerged as a promising therapeutic strategy for targeted protein degradation. However, the clinical application of PROTACs may be hindered by off-target toxicity resulting from non-tissue-specific protein degradation and ingenious prodrug strategies may open new avenues to addressing this concern. Herein, we propose a light-induced positive feedback strategy to use photodynamic therapy (PDT) to improve the activation efficiency of PROTAC prodrugs, monitor PROTAC release, and combine PROTAC to induce tumor cell apoptosis. In the hypoxic tumor microenvironment, the azo bond in AZO-PRO selectively cleaves, triggering the release of the potent protein degrader PRO and the multifunctional photosensitizer. Once activated, the fluoresce signal of the photosensitizer dramatically recovers, allowing monitoring of prodrug activation. Additionally, upon irradicating the tumor site using near-infrared (NIR) laser, PDT exacerbates tumor hypoxia, further promoting AZO-PRO activation. Our work introduces a novel approach to efficiently track and activate PROTAC prodrugs, enhance their antitumor efficacy, and mitigate off-target systemic toxicity.

Alzheimer's disease (AD) is characterized by cognitive and functional deterioration, with pathological features such as amyloid-beta (Aβ) aggregates in the extracellular spaces of parenchymal neurons and intracellular neurofibrillary tangles formed by the hyperphosphorylation of tau protein. Despite a thorough investigation, current treatments targeting the reduction of Aβ production, promotion of its clearance, and inhibition of tau protein phosphorylation and aggregation have not met clinical expectations, posing a substantial obstacle in the development of drugs for AD. Recently, artificial intelligence (AI), computational biology (CB), and systems biology (SB) have emerged as promising methodologies in AD research. Their capacity to analyze extensive and varied datasets facilitates the identification of intricate patterns, thereby enriching our comprehension of AD pathology. This paper provides a comprehensive examination of the utilization of AI, CB, and SB in the diagnosis of AD, including the use of imaging omics for early detection, drug discovery methods such as lecanemab, and complementary therapies like phototherapy. This review offers novel perspectives and potential avenues for further research in the realm of translational AD studies.

Objective:To investigate the expression of keratin 1 (KRT1) and sialyl-Tn antigen (sTn) in cervical squamous cell carcinoma and its possible mechanism.Methods:Six cervical squamous cell carcinoma specimens were collected at the First Affiliated Hospital of Soochow University, Suzhou, China from 2022 to 2023. Spatial transcriptomics analysis was performed on the paraffin sections of 6 patients to analyze the transcriptomes of invasive squamous cell carcinoma and adjacent normal cervical squamous epithelium. The differential gene KRT1 was selected. Kaplan-Meier survival analysis was used to examine the prognostic value of KRT1 in cervical squamous cell carcinoma patients using the TCGA database. The possible downstream molecule sTn was identified according to literature research. Immunohistochemistry was carried out to investigate the expression of KRT1 and sTn proteins in the primary tumor and metastases of cervical squamous cell carcinoma (40 cases with pelvic lymph node metastasis and 30 cases without). Spearman correlation analysis was conducted to analyze the correlation of their expression.Results:The spatial transcriptomic results of the 6 specimens indicated that the level of KRT1 mRNA significantly decreased in cervical squamous cell carcinoma (compared with that in adjacent normal cervical squamous epithelium), while Kaplan-Meier survival analysis revealed that cervical squamous cell carcinoma patients with low KRT1 mRNA levels (versus high) had a worse prognosis. Immunohistochemistry proved that KRT1 expression was significantly lower in cervical squamous cell carcinoma than in adjacent normal squamous epithelium ( P<0.05), but sTn showed the opposite change (increased in carcinoma, P<0.05). The expression changes of KRT1 and sTn were inversely correlated ( r=-0.217, P<0.05). In addition, the expression levels of KRT1 and sTn in lymph node metastases were not significantly different from those in primary tumors. Conclusions:The decreased expression of KRT1 in primary cervical squamous cell carcinoma and lymph node metastasis may promote tumor cell proliferation and inhibit apoptosis by upregulating sTn, contributing to the poor prognosis of advanced cervical squamous cell carcinoma.

Trifluridine-tipiracil(TAS-102),as a novel fluorouracil-based chemotherapeutic agent,effectively overcomes fluorouracil resistance in colorectal cancer(CRC)through its unique pharmacological mechanisms,providing a critical treatment option for advanced CRC patients.Probiotics have shown unique value in CRC prevention and adjuvant therapy by regulating intestinal flora homeostasis and modulating host immune response.It is worth noting that the combination of chemotherapeutic drugs and probiotics not only enhances the anti-tumor activity through synergistic effects,but also reduces the adverse effects caused by chemotherapeutic drugs.Based on this,this paper systematically reviews the pharmacological properties of TAS-102 and describes its synergistic effects in combination with other antitumor drugs.It also summarizes the synergistic effect of fluorouracil drugs combined with probiotics to enhance the effectiveness and reduce the toxicity,and discusses the potential value of the combination of TAS-102 and probiotics,which provides a new research direction for optimizing the precision treatment of CRC and a scientific basis for improving the quality of life of patients.

Objective:To analyze risk factors for early trauma-induced coagulopathy (TIC) in pediatric patients with moderate-to-severe traumatic brain injury (msTBI), develop a predictive model and evaluate its predictive performance.Methods:A retrospective cohort study was conducted to analyze the clinical data of 290 pediatric patients with msTBI who were admitted to Children′s Hospital of Soochow University between January 2016 and December 2024, including 188 boys and 102 girls, aged 0.2-15.7 years [5.2(2.8, 9.3)years]. Based on the coagulation test results at admission, the patients were divided into TIC group ( n=162) and non-TIC group ( n=128). The patients were randomly allocated into training set ( n=203) and validation set ( n=87) at a ratio of 7∶3. Demographic characteristics, clinical data, vital signs, imaging findings, arterial blood gas analysis results, and coagulation profiles of the patients were collected. Univariate analysis and Lasso regression analysis were used to identify risk factors associated with early TIC in children with msTBI and multivariate Logistic regression analysis was performed to determine independent risk factors and construct a predictive model. The model′s discrimination and calibration were evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), Hosmer-Lemeshow (H-L) test, and calibration curve. Its clinical utility was assessed through decision curve analysis (DCA). Results:Significant differences were observed between the TIC group and non-TIC group in terms of age, weight, time from injury to admission, child′s Glasgow coma scale (CGCS) score, pediatric trauma score (PTS), shock index, heart rate, respiratory rate, systolic blood pressure, Rotterdam CT score, intraventricular hemorrhage, cerebral contusion, brain herniation, long bone fracture, pelvic fracture, hemopneumothorax, pulmonary contusion, intra-abdominal organ injury, actual bicarbonate, base excess, base excess in the extracellular fluid, blood glucose, hemoglobin (Hb), osmolarity, blood calcium, anion gap, blood lactate, prothrombin time, activated partial thromboplastin time, international normalized ratio, and platelet count ( P<0.05). With coagulation-related variables excluded, the following features were identified with Lasso regression including CGCS score, PTS, heart rate, systolic blood pressure, long bone fracture, blood glucose, and Hb. Multivariate Logistic regression analysis revealed that CGCS score≤8 points ( OR=3.05, 95% CI 1.65, 5.63), PTS>5 points ( OR=0.45, 95% CI 0.23, 0.89), systolic blood pressure ( OR=0.98, 95% CI 0.97, 0.99), blood glucose ( OR=1.09, 95% CI 1.01, 1.17), and long bone fracture ( OR=2.47, 95% CI 1.13, 5.42) were influencing factors for early TIC in children with msTBI ( P<0.05). The regression equation of the predictive model was established as follows: Logit[ P/(1- P)]=1.01×"CGCS score≤8 points"-0.69×"PTS>5 points"- 0.02×"systolic blood pressure"+0.89×"long bone fracture"+0.08×"blood glucose"+1.32. The ROC curve analysis showed that the training set had an AUC of 0.86 (95% CI 0.78, 0.94), with sensitivity and specificity of 76.6% and 92.5%, while the AUC was 0.80 (95% CI 0.74, 0.86), with sensitivity and specificity of 75.7% and 79.6% in the validation set. H-L test results showed a χ2 value of 8.18 ( P=0.416) in the training set and 5.30 ( P=0.216) in the validation set. The calibration curves for both sets demonstrated good agreement with the actual curves, indicating that the predicted probabilities closely matched the observed probabilities. The DCA results indicated that both the training set and validation set demonstrated positive net benefits within threshold probabilities ranges of 10%-100% and 15%-96%. Conclusions:Independent risk factors for early TIC in pediatric msTBI patients include CGCS score≤ 8 points, PTS≤5 points, low systolic blood pressure, long bone fracture, and high blood glucose. The predictive model constructed based on these factors demonstrates favorable predictive performance and clinical application value.

Objective:Hearing loss can seriously affect mental health status, and this study aims to investigate the influence of hearing health status on depressive symptoms among middle-aged and older individuals in the community.Methods:From June to December 2023, a stratified random sampling method was employed to select 1 238 community-dwelling middle-aged and elderly people aged 45 years and above from four cities (Hangzhou, Shanghai, Baoding, and Zhengzhou) as research subjects. A questionnaire survey was conducted to collect the subjects′ basic information, hearing health status [assessed by the Hearing Handicap Inventory for Adults-Screening Version (HHIA-S)], and depressive symptoms [assessed by the Geriatric Depression Scale-15 (GDS-15)]. T-tests, rank-sum tests and chi-square tests were used for univariate analysis, while, multiple linear regression and binary Logistic regression were applied to analyze the relationship between hearing health status and depressive symptoms.Results:A total of 1 183 community-dwelling middle-aged and elderly people aged 45 years and above were included in the final analysis (464 males and 719 females, aged from 45 to 96 years). The detection rate of hearing loss was 35.3%(418/1 183), while, the detection rate of depressive symptoms was 9.89%(117/1 183). Age, level of interaction with children, self-rated health, perceived loneliness, and hearing health significantly influenced depressive symptoms among older adults residing in the community ( P<0.05). Individuals with moderate to severe hearing loss ( β=2.04, 95% CI: 1.47, 2.62) exhibited higher GDS-15 scores compared to those without hearing impairment. Furthermore, after correcting for sex, age, marital status, monthly per capita family income, education, residence, smoking status, alcohol use, use of psychotropic medication (anxiolytic or depressant), number of illness, self-health assessment, and autonomy, middle-aged and older adults with mild to moderate hearing loss ( OR=2.89, 95% CI: 1.76, 4.88) and severe hearing loss ( OR=5.79, 95% CI: 3.05, 11.01) demonstrated an increased likelihood of experiencing depression. Conclusions:The degree of hearing loss in community-dwelling middle-aged and elderly individuals is closely associated with the risk of depressive symptoms. Therefore, it is imperative to enhance hearing health screening and to provide mental health support to individuals with hearing loss, in order to mitigate the onset and progression of depressive symptoms.

Objective:To investigate the association between hearing loss and the type of indoor fuel applications in Chinese middle-aged and elderly people through longitudinal cohort study.Methods:Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS), including adults aged 45 years and older enrolled in 2011, with follow-up for cooking and heating analyses extending to 2018 and 2015, respectively. The study calculated the incidence of hearing loss based on an indoor cooking or heating fuel type and expressed in terms of per 100 person-years. The Cox proportional hazard model was used to assess the association between solid fuel use and hearing loss, and covariates such as gender, education, and economy were controlled. We also analyzed the impact of indoor fuel type and its switching on hearing loss.Results:A total of 6, 772 participants using household fuels for cooking (2011-2018) and 4, 618 for heating (2011-2015) were included. Those using solid fuels for cooking [(58.0±8.2) years] and heating [(58.1±8.5) years] were generally slightly older than that of those who used clean fuels. In the cooking analysis, the overall incidence of hearing loss was higher among solid fuel users compared to clean fuel users (Clean fuel: 2.6 cases per 100 person-years; solid fuel: 3.6 cases per 100 person-years; the difference between the two was statistically significant, P<0.05). However, no significant difference was observed in the heating analysis ( P>0.05). Further classification of fuel-type use revealed that the incidence of hearing loss was the highest among people who had been using solid fuels consistently. Compared to the clean fuel group, the fully adjusted hazard ratio (HR) was 1.5 (95% CI: 1.3-1.7) in the cooking analysis and 1.5 (95% CI: 1.1-2.0) in the heating analysis. Compared with using clean fuels, switching from clean fuels to solid fuels increased the risk of hearing loss both during cooking and heating processes. Conclusion:In the CHARLS database, individuals who use solid fuels for indoor cooking and heating are older than those who use clean fuels. Compared with clean fuel use, the use of solid fuels increases the risk of hearing loss in middle-aged and elderly people. Reducing the use of solid fuels, choosing clean fuels as substitutes for solid fuels, and avoiding the switch from clean fuels to solid fuels will help protect the hearing health of middle-aged and elderly individuals.

Chronic obstructive pulmonary disease(COPD)often leads to disease progression due to"inflammation extravasation"and development to the whole body"weakness".Professor Miao Qing believes that"disorder of qi movement,impairment of the descending function of the lung"is the key pathogenesis of COPD,and proposes the method of"mediating triple energizers and tonifying three qi"to treat COPD,that is,based on upper energizer-pectoral qi-heart and lung qi,middle energizer-middle qi-spleen-stomach qi,lower energizer-primordial qi-kidney qi and kidney essence,respectively,"raising pectoral qi,nourishing upper energizer heart and lung","cultivating and nourishing middle qi,balancing the spleen and stomach of middle energizer","reinforcing the primordial qi,collecting and absorbing the kidney essence of lower energizer",and achieved good efficacy.