ObjectiveTo explore the role of neuroimaging features monitored by functional near-infrared spectroscopy （fNIRS） in postoperative delirium （POD） in elderly patients undergoing joint replacement during perioperative period， and to provide a basis for early clinical prediction. MethodsA total of 105 elderly patients who underwent joint replacement under general anesthesia were included. The Mini-Mental State Examination （MMSE） scale was used to evaluate the patient's cognition one day before the operation. Before the start of the surgery， fNIRS was used to monitor the changes of cerebral blood oxygen saturation when the patient performed the task state. The 3-minute delirium diagnostic scale （3D-CAM scale） was used to evaluate the occurrence of POD at 24， 48 and 72 h after operation. Brain network analysis was performed and Logistic regression analysis was used to explore the relationship between fNIRS monitoring data and POD in elderly patients undergoing joint replacement surgery during preoperative task state. The receiver operating characteristic curve （ROC curve） was constructed to evaluate the diagnostic efficacy， and the Hosmer-Lemeshow goodness-of-fit test was used to test the goodness of fit of the model. ResultsAmong 105 patients， 100 cases were effectively analyzed， of which 20 cases （20%） had POD. Brain network analysis showed that the r value of functional connectivity correlation coefficient in POD group （0.069±0.118） was lower than that in non-POD group （0.073±0.084）. The low channel connectivity of right primary somatosensory cortex-right primary motor cortex （RS1-RM1） and left anterior pole-right Broca's triangle （LFP-RBA44） was an important factor affecting the occurrence of POD （P < 0.05）. Based on this result， the area under the ROC curve was 0.797 and 0.784， respectively. The results of Hosmer-Lemeshow goodness-of-fit test showed that the model fitted well （all P>0.5）. ConclusionThe neuroimaging features extracted from the cerebral oxygen saturation data monitored by fNIRS are significantly correlated with the risk of POD in elderly patients undergoing joint replacement during perioperative period. Among them， the low connectivity of preoperative RS1-RM1 and LFP-RBA44 brain network channels is an important influencing factor of POD occurrence. Predicting the occurrence of POD based on fNIRS is conducive to the early intervention and risk reduction of perioperative complications， improving medical quality and promoting precision medical practice.

Objective: To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. Methods: Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue. Results: Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated. Conclusion Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.

ObjectiveTo analyze the impact of diabetes-related deaths on the probability of premature mortality and life expectancy in Minhang District of Shanghai from 2004 to 2023, and to provide reference data for the optimization of targeted prevention and control strategies. MethodsAll death cases involving diabetes among the registered residents of Minhang District from 2004 to 2023 were collected. The probability of premature mortality and life expectancy was computed using the abridged life table method. The average annual percent change (AAPC) was calculated with Joinpoint 4.9.0.0. The Arriaga decomposition method was employed for statistical analyses of the influence of cause-specific and age-specific mortality related to diabetes on life expectancy. ResultsThe total number of diabetes-related mortality, crude mortality, and standardized mortality for both males and females in Minhang District from 2004 to 2023 exhibited an increasing trend (P<0.001). The primary causes of death among diabetes-related cases were cardiovascular disease (37.68%), diabetes mellitus (31.95%), and malignant tumor (17.80%). From 2004 to 2023, probability of premature mortality to diabetes-related diseases demonstrated a rising trend (P<0.001), contrasting with the declining trend observed in the overall population (P=0.001). Males showed a significant upward trajectory (P<0.001), while females displayed a stable pattern. Among the diseases exerting considerable influence, cardiovascular disease and malignant tumor revealed a marked increase over time (P<0.001), whereas diabetes mellitus maintained a stable trend; both factors negatively impacted the reduction in probability of premature mortality. From 2004 to 2023, diabetes-related mortality reduced life expectancy among residents by an average of 1.22 years (-49.89%), indicating a negative impact; the reduction was 1.41 years in males and 0.90 years in females. The age groups exhibiting greater negative contributions differed by genders, namely males aged 50‒54 years and females aged 70‒74 years. Cardiovascular disease, diabetes mellitus, and malignant tumor contributed significantly to this decline (-0.46 years, -0.42 years, -0.20 years, respectively), with male experiencing higher negative contributions than females. ConclusionIn Minhang District, the rising mortality associated with diabetes-related diseases negatively impact both the reduction of the probability of premature mortality and the increase in life expectancy. This trend is primarily attributed to the rapid escalation of mortality and younger age demographic of male residents, which warrants significant attention. It is recommended that, based on the enhancement of case management, efforts should be directed towards the targeted prevention and control of risk factors and high-risk populations.

Invasive angiomyxoma（AAM） is characterized by unclear boundaries, non enveloped glial growth, high recurrence rate, and belongs to a benign tumor, but it is invasive and grows slowly. A patient with recurrent left vestibular invasive angiomyxoma was admitted to the Otorhinolaryngology ward of Beijing Traditional Chinese Medicine Hospital Affiliated with Capital Medical University. The patient underwent two repeated surgeries and underwent a combined internal and external nasal approach for the removal of the nasal vestibular angiomyxoma. The patient recovered well after the surgery and has not recurred since follow-up.
Humans ; Myxoma/pathology* ; Neoplasm Recurrence, Local ; Nose Neoplasms/pathology*

Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL_(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL_(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.

Objective To investigate the incidence and economic burden of healthcare-associated infection(HAI)in patients after liver transplant.Methods Basic clinical information,infection status,and related medical expenses of liver transplant patients in the department of hepatobiliary surgery in a tertiary first-class hospital from November 2012 to December 2023 were investigated retrospectively.A case-control study design was employed,with post-li-ver transplant patients who developed HAI as the infection group and those without HAI during the same period as the control group.The 1∶1 propensity score matching(PSM)method was adopted(caliper value was set at 0.05,employing sampling without replacement).Length of hospital stay and hospitalization expenses between patients in the infection group and the control group were compared using Wilcoxon rank-sum test,and the economic burden due to HAI was calculated.Results A total of 336 liver transplant patients were included in study,out of which 48 had HAI,with an incidence of 14.29％.44 pairs were successfully matched by PSM.After matching,the median hospitalization expense for patients in the infection group was 334 473.73 Yuan,while that of the control group was 285 824.82 Yuan,with a statistically significant difference(Z=-3.430,P＜0.05).The direct economic burden of HAI in liver transplant patients was 48 648.91 Yuan.After matching,the median length of hospital stay in the in-fection group(37.0 days)was 12.5 days longer than that in the control group(24.5 days),with statistically sig-nificnat difference(Z=-3.630,P＜0.001).Conclusion HAI after liver transplant increases patients' hospitaliza-tion expense and prolongs their hospital stay,thus brings huge economic burdens to the patients.

OBJECTIVE The emergence of evolving variants of Coronavirus disease 2019(COVID-19)has fostered the need for change of newer and adaptive treatments for these infections.During the COVID-19 pandemic and persists,traditional Chinese medicine(TCM)herbs exhibit significant bioactivity and therapeutic effect.This study is aimed to evaluate the efficacy of four TCM preparations on 28-day mortality risk of patients and changes of the laboratory indicators.METHODS The retrospective cohort study included patients with COVID-19 who were admitted to the Jiangsu Province Hospital of Chinese Medicine from December 15,2022 to January 15,2023,and those died within 48 hours of admission or cannot be tracked for outcomes were excluded.The pri-mary outcome was survival status in 28 days(death or survival)starting from the day of admission.The second outcomes were labora-tory indicators,including absolute lymphocyte count,lactate dehydrogenase,creatinine,and blood urea nitrogen.Binary logistic re-gressions were used to estimate the effect of TCM preparations on the primary and secondary outcomes in main analysis.Meanwhile,heterogeneity and robustness of results from main analysis were assessed by subgroup analyses and multiple sensitivity analyses.RESULTS 1 816 eligible patients were included in analysis dataset,including 573 patients received standard care(control group)and 1 243 patients received TCM preparations(hospital preparation group).The 28-day mortality rate of hospital preparation group was lower than that of control group(4.75%vs.14.83%),and the difference was statistically significant(χ2=54.666,P<0.001).The risk of 28-day mortality was 0.535 times lower in the hospital preparation group as compared with the control group(OR=0.46,95%CI:0.305-0.708,P<0.001)showed by multivariable binary logistic regressions.Subgroup analyses showed that taking TCM preparations reduced the 28-day mortality risk.Sensitivity analyses demonstrated that the results of the main analysis for primary outcomes were robust.For secondary outcomes,the risk of abnormal absolute lymphocyte counts at discharge in the hospital prepara-tion group decreased by 0.284 times(OR=0.703,95%CI:0.515-0.961,P=0.027).CONCLUSION Compared with standard of care,taking four hospital preparations including Kanggan Heji,Feining Heji,Qishen Gubiao Keli,and Qianghuo Qushi Qingwen Heji decreased risk of 28-day mortality among hospitalized COVID-19 patients.TCM therapy achieves adequate therapeutic effects in COVID-19.

Objectives:This study aims to explore the value of the baseline extracellular volume(ECV)measured by cardiac magnetic resonance(CMR)in predicting cardiac response in patients with light chain cardiac amyloidosis(AL-CA)after treatment.Methods:This single-center retrospective cohort study included AL-CA patients diagnosed between May 2020 and March 2023.Baseline ECV measurement and other relevant parameters were derived from CMR.Therapeutic cardiac response was assessed through serial measurements of N-terminal pro-B-type natriuretic peptide(NT-proBNP).Complete recovery was defined as achieving NT-proBNP≤350 pg/ml post-treatment.Patients demonstrating>60%reduction from baseline NT-proBNP without attaining complete response criteria were classified as very good partial recovery.Those showing 31%-60%decreases from baseline NT-proBNP without meeting the threshold for very good partial recovery were qualified as partial recovery,while≤30%reductions from baseline were considered as non-recovery.The study evaluated two endpoints:the initial emergence of any cardiac recovery(encompassing partial recovery,very good partial recovery,or complete recovery)and the subsequent attainment of optimal cardiac recovery(encompassing partial recovery,very good partial recovery,or complete recovery).The patients were divided into two groups based on whether they experienced cardiac recovery at the end of follow-up:the recovery group(n=24,comprising 7 with partial recovery,14 with very good partial recovery,and 3 with complete recovery)and the non-recovery group(n=16).Cox Proportional hazards regression models were used to analyse the impact of baseline ECV on the cardiac recovery.The Kaplan-Meier method and log-rank test were used to assess and compare the probability and timing of cardiac recovery between different baseline ECV groups.Results:Among the 40 patients,28(70%)were male,with a mean age of(58?±?8)years.32 patients(80%)had the λ subtype of AL-CA.During a median follow-up of 568(155,1 049)days,15 patients showed partial cardiac recovery at 60 days post-treatment,and 3 patients achieved very good partial cardiac recovery;by 720 days of treatment and until the end of follow-up,3 patients achieved complete cardiac recovery.Multivariate Cox regression analysis revealed that baseline ECV(HR=0.937,95%CI:0.879-0.999,P=0.045)and daratumumab-based regimens(HR=3.279,95%CI:1.098-9.796,P=0.033)were significant predictors of the initial cardiac recovery.Similarly,baseline ECV(HR=0.931,95%CI:0.867-1.000,P=0.048)and daratumumab-based regimens(HR=3.132,95%CI:1.052-9.319,P=0.040)were also independent predictors for the best cardiac recovery.Kaplan-Meier analysis demonstrated that patients with baseline ECV<54%achieved an earlier first cardiac recovery than those with baseline ECV≥54%(log-rank P=0.014)and the group with baseline ECV<55%were more likely to achieve the best cardiac recovery compared to those with baseline ECV≥55%(log-rank P=0.006).Conclusions:Baseline ECV measured by CMR can serve as an independent predictor of cardiac recovery in AL-CA patients after treatment.Lower baseline ECV levels are associated with a faster and more favorable cardiac recovery.The daratumumab-based regimens demonstrated superior cardiac recovery outcomes.

Objective This study examined the association between smoking and cognitive decline through a cohort in rural population in Xi'an.Methods Data were collected from the cognitive impairment cohort of middle-aged and elderly people in rural areas of Xi'an.The cohort selected the population aged 40 years and above in rural Xi'an.The baseline survey was completed between October 2014 and March 2015,and two follow-up visits were conducted in 2016 and 2018.This study took the baseline cognitively normal population of this cohort as the research subjects.According to the survey results in 2018,the population was divided into three groups according to smoking status:smoking,quitting and non-smoking.Cognitive function was assessed by Mini-Mental State Examination(MMSE).△MMSE(2014 rating-2018 rating)≥2 was defined as cognitive decline,and △MMSE＜2 was defined as cognitive stability.Binary Logistic regression model and stratified analysis were used to analyze the relationship between smoking and cognitive decline and the influence of age on the relationship.Results A total of 1 289 subjects were included in this study.According to smoking status in 2018,they were divided into non-smokers(910,70.6％),smokers(335,26.0％),and ex-smokers(44,3.4％).In the total population,there was no significant difference in the incidence of cognitive decline among non-smokers,smokers and ex-smokers(17.3％vs.16.1％vs.15.9％,P=0.880).When stratified by age,there was no significant difference in the incidence of cognitive decline among the three groups in the subgroup of age＜65 years(16.5％vs.13.2％vs.12.1％,P=0.365).In the subgroup of age≥65 years,no significant difference was found in the incidence of cognitive decline among non-smokers,smokers and ex-smokers(20.8％vs.30.9％vs.27.3％,P=0.306).After adjusting for confounding factors,smokers had a significantly higher risk of cognitive decline than non-smokers(OR=14.139;95％CI:1.541-129.705;P=0.019).There was a trend of cognitive decline in the ex-smokers group,but with no statistical significance(OR=8.252;95％CI:0.630-108.175;P=0.108).Conclusion Smoking is positively associated with cognitive decline in the elderly,suggesting that smoking may accelerate cognitive decline in this population.

Kaempferol(KAE),as a natural flavonoid compound,possesses multiple biological activities including po-tent anti-inflammatory,antioxidant,and immunomodulatory effects,as well as anti-cancer properties.It has demonstrated good therapeutic effects in the intervention and treatment of various ocular diseases such as fungal keratitis,corneal trans-plantation rejection,age-related macular degeneration,and diabetic retinopathy.Furthermore,the development of novel ocular drug delivery systems-such as KAE-loaded bovine serum albumin porous membranes,KAE eye drops based on poly-vinylpyrrolidone nanocomplexes,gelatin nanoparticles encapsulating KAE,and platelet-derived extracellular vesicles loaded with KAE-has improved the bioavailability of KAE,laying a foundation for expanding its applications.However,there is a lack of systematic and comprehensive reviews on the application of KAE in ophthalmic diseases.Therefore,this article summarizes the research progress,efficacy mechanisms,and novel delivery methods of KAE in ophthalmic diseases,ai-ming to provide new diagnostic and therapeutic strategies for the treatment of related ocular conditions.