Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, functional impairment, and neuropsychiatric symptoms. It represents the most prevalent form of dementia among the elderly population. Accumulating evidence indicates that oxidative stress plays a pivotal role in the pathogenesis of AD. Notably, elevated levels of oxidative stress have been observed in the brains of AD patients, where excessive reactive oxygen species (ROS) can cause extensive damage to lipids, proteins, and DNA, ultimately compromising neuronal structure and function. Amyloid β‑protein (Aβ) has been shown to induce mitochondrial dysfunction and calcium overload, thereby promoting the generation of ROS. This, in turn, exacerbates Aβ aggregation and enhances tau phosphorylation, leading to the formation of two pathological features of AD: extracellular Aβ plaque deposition and intracellular neurofibrillary tangles (NFTs). These events ultimately culminate in neuronal death, forming a vicious cycle. The interplay between oxidative stress and these pathological processes constitutes a core link in the pathogenesis of AD. The signaling pathways mediating oxidative stress in AD include Nrf2, RCAN1, PP2A, CREB, Notch1, NF‑κB, ApoE, and ferroptosis. Nrf2 signaling pathway serves as a key regulator of cellular redox homeostasis, exerts important antioxidant capacity and protective effects in AD. RCAN1 signaling pathway, as a calcineurin inhibitor, and modulates AD progression through multiple mechanisms. PP2A signaling pathway is involved in regulating tau phosphorylation and neuroinflammation processes. CREB signaling pathway contributes to neuroplasticity and memory formation; activation of CREB improves cognitive function and reduce oxidative stress. Notch1 signaling pathway regulates neuronal development and memory, participates in modulation of Aβ production, and interacts with Nrf2 toco-regulate antioxidant activity. NF‑κB signaling pathway governs immune and inflammatory responses; sustained activation of this pathway forms “inflammatory memory”, thereby exacerbating AD pathology. ApoE signaling pathway is associated with lipid metabolism; among its isoforms, ApoE-ε4 significantly increases the risk of AD, leading to elevated oxidative stress, abnormal lipid metabolism, and neuroinflammation. The ferroptosis signaling pathway is driven by iron-dependent lipid peroxidation, and the subsequent release of lipid peroxidation products and ROS exacerbate oxidative stress and neuronal damage. These interconnected pathways form a complex regulatory network that regulates the progression of AD through oxidative stress and related pathological cascades. In terms of therapeutic strategies targeting oxidative stress, among the drugs currently used in clinical practice for AD treatment, memantine and donepezil demonstrate significant therapeutic efficacy and can improve the level of oxidative stress in AD patients. Some compounds with antioxidant effects (such asα-lipoic acid and melatonin) have shown certain potential in AD treatment research and can be used as dietary supplements to ameliorate AD symptoms. In addition, non-drug interventions such as calorie restriction and exercise have been proven to exerted neuroprotective effects and have a positive effect on the treatment of AD. By comprehensively utilizing the therapeutic characteristics of different signaling pathways, it is expected that more comprehensive multi-target combination therapy regimens and combined nanomolecular delivery systems will be developed in the future to bypass the blood-brain barrier, providing more effective therapeutic strategies for AD.

This study explores the effect and mechanism of Banxia Xiexin Decoction(BXD) in inhibiting colon cancer progression by reshaping tryptophan metabolism. Balb/c mice were assigned into control, model, low-dose BXD(BXD-L), and high-dose BXD(BXD-H) groups. Except the control group, the other groups were subcutaneously injected with CT26-Luc cells for the modeling of colon cancer, which was followed by the intervention with BXD. Small animal live imaging was employed to monitor tumor growth, and the tumor volume and weight were measured. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in mouse tumors. Immunohistochemistry was used to detect Ki67 expression in tumors. Immunofluorescence and flow cytometry were used to detect the infiltration and number changes of CD3~+/CD8~+ T cells in the tumor tissue. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interferon-gamma(IFN-γ) and interleukin-2(IL-2) in tumors. Targeted metabolomics was employed to measure the level of tryptophan(Trp) in the serum, and the Trp content in the tumor tissue was measured. Western blot and RT-qPCR were employed to determine the protein and mRNA levels, respectively, of indoleamine 2,3-dioxygenase 1(IDO1), MYC proto-oncogene, and solute carrier family 7 member 5(SLC7A5) in the tumor tissue. Additionally, a co-culture model with CT26 cells and CD8~+ T cells was established in vitro and treated with the BXD-containing serum. The cell counting kit-8(CCK-8) assay was used to examine the viability of CT26 cells. The content of Trp in CT26 cells and CD8~+ T cells, as well as the secretion of IFN-γ and IL-2 by CD8~+ T cells, was measured. RT-qPCR was used to determine the mRNA levels of MYC and SLC7A5 in CT26 cells. The results showed that BXD significantly inhibited the tumor growth, reduced the tumor weight, and decreased the tumor volume in the model mice. In addition, the model mice showed sparse arrangement of tumor cells, varying degrees of patchy necrosis, and downregulated expression of Ki67 in the tumor tissue. BXD elevated the levels of IFN-γ and IL-2 in the tumor tissue, while upregulating the ratio of CD3~+/CD8~+ T cells and lowering the levels of Trp, IDO1, MYC, and SLC7A5. The co-culture experiment showed that BXD-containing serum reduced Trp uptake by CT26 cells, increased Trp content in CD8~+T cells, enhanced IL-2 and IFN-γ secretion of CD8~+T cells, and down-regulated the mRNA levels of MYC and SLC7A5 in CT26 cells. In summary, BXD can inhibit the MYC/SLC7A5 pathway to reshape Trp metabolism and adjust Trp uptake by CD8~+ T cells to enhance the cytotoxicity, thereby inhibiting the development of colon cancer.
Animals ; Tryptophan/metabolism* ; Colonic Neoplasms/pathology* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred BALB C ; Humans ; Cell Line, Tumor ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism* ; Female ; Disease Progression ; Cell Proliferation/drug effects* ; Proto-Oncogene Mas ; Male

Purpose::Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation.Methods::C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference. Results::Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol.Conclusions::Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.

Objective To explore the relationship and internal path between activities of daily living(ADL),sleep quality and mental health of community elderly people in Shanghai.Methods A questionnaire survey was conducted among community residents aged 60 years and older seeing doctors in community health care center of five streets in Shanghai during Sept to Dec,2021 using convenience sampling.Activities of Daily Living(ADL),Pittsburgh Sleep Quality Index(PSQI)and 10-item Kessler Psychological Distress Scale(K10)were adopted in the survey.Single factor analysis,correlation analysis and multiple linear regression were used to analyze the data.The effect relationship between the variables was tested using Bootstrap's mediated effects test.Results A total of 1 864 participants were included in the study.The average score was 15.53±4.47 for ADL,5.60±3.71 for PSQI and 15.50±6.28 for K10.The rate of ADL impairment,poor sleep quality,poor and very poor mental health of the elderly were 23.6%,27.3%,11.9%and 4.9%,respectively.ADL and sleep quality were all positively correlated with mental health(r=0.321,P＜0.001;r=0.466,P＜0.001);ADL was positively correlated with sleep quality(r=0.294,P＜0.001).Multiple linear results of factors influencing mental health showed that ADL(β= 0.457,95%CI:0.341-0.573),sleep quality(β =0.667,95%CI:0.598-0.737)and mental health were positively correlated(P＜0.001).Sleep quality partially mediated the relationship between ADL and mental health(95%CI:0.078-0.124)with an effect size of 33.0%.Conclusion Sleep quality is a mediator between ADL and mental health among community elderly people.Improving ADL and sleep quality may improve mental health in the population.

Cervical spondylotic radiculopathy(CSR)is a condition caused by the degeneration of cervical intervertebral discs and facet joints,primarily manifesting as the pain,sensory abnormalities,and motor dysfunction in the cervical nerve innervation area of neck,shoulder,and upper limb.For the treatment of CSR,tendon-bone syndrome differentiation in traditional Chinese medicine often faces the issues of conceptual confusion and non-standard syndrome differentiation.Based on the traditional tendon-bone syndrome differentiation and by integrating modern anatomical insights,Professor LIN Ding-Kun,an esteemed scholar of Traditional Chinese Medicine,proposed a classification system for the cervical spine that includes the categories of tendons,joints,bones and marrow.This paper explored the thoughts of Professor LIN for the tendon-bone syndrome differentiation of CSR,summarized the targets of manual therapy,and proposed the four kinds of pathological changes such as tendon overstrain,joint dislocation,bone lesion,and marrow injury,as well as the four techniques of traditional Chinese medicine manipulations,i.e.relaxation of tendons,reduction of joints,protection of marrow,and treatment of bones.The aim is to improve the syndrome-differentiation and treatment for CSR with orthopedic and traumatologic manipulations,and to provide reference for clinical practice.

Objective To investigate the value of wrist MRI in bone age estimation for male adoles-cents in Shanghai,Zhejiang and Jiangsu.Methods A total of 124 Han male adolescents aged 6.0 to 18.0 years from Shanghai,Zhejiang and Jiangsu were selected as subjects.Their weight and height were measured,and T1WI and T2WI sequences of the wrist were scanned.The distal ends of the ra-dius and ulna,and the first to five metacarpal epiphyses and corresponding metaphyses were selected as observational indexes after MRI images of the wrist were obtained.The development of each index was classified(0-2 grades)by a deputy senior imaging expert,then the maximum width of each in-dex was measured by another deputy senior expert.Height,weight,classification and maximum width of indexes were used as input variables,and age was used as the target variable.Support vector ma-chine,random forest,current reality tree,and linear regression models were established to estimate the bone age,and the model with the highest accuracy was selected.Results The height,weight,classifica-tion of wrist bone epiphysis development,maximum width of each bone metaphysis and epiphysis were all correlated with age(P<0.05).The accuracies of the support vector machine were the highest when the differences between bone age and actual chronological age were within 1.0 and 1.5 years(88.7%and 96.0%,respectively).Conclusion It is feasible to estimate bone age by using MRI images.Quantifying the maximum width of the epiphysis and corresponding metaphysis of bone and combining it with MRI image classification can effectively reduce the estimation error.

Objective To analyze the characteristics of drug resistance in patients with disseminated pulmonary tuberculosis,and provide references for the clinical development of individualized treatment plans.Methods A retrospective analysis was conducted on 71 hospitalized patients with disseminated pulmonary tuberculosis treated at the Beijing Chest Hospital,Capital Medical University from January 2015 to January 2024.The susceptibility of Mycobacterium tuberculosis from these patients to 16 anti-tuberculosis drugs was detected using the microplate method for mycobacterial drug susceptibility testing.The study analyzed the culture results of Mycobacterium tuberculosis,drug susceptibility test results,initial treatment or re-treatment status,drug resistance,and differences in drug resistance types between initial and re-treated patients.Results Among the 71 patients with disseminated pulmonary tuberculosis,there were 51 males(71.8%),and 58 cases(81.7%)of acute disseminated pulmonary tuberculosis,with an overall drug resistance rate to 16 anti-tuberculosis drugs of 38.0%.There was no statistically significant difference in the total drug resistance rate between re-treated patients and those undergoing initial treatment[52.2%(12/23)vs.31.3%(15/48),P=0.089].The top 7 drugs to which patients were resistant were streptomycin(Sm)and isoniazid(INH)with 13 cases each(18.3%),rifapentine(Rft)and isoniazid aminosalicylate(Pa)with 10 cases each(14.1%),rifampicin(RFP),rifabutin(Rfb),and capreomycin(Cm)with 9 cases each(12.7%).The top 6 drugs to which initially treated patients were resistant were Cm with 6 cases(12.5%),Sm with 5 cases(10.4%),Pa with 4 cases(8.3%),INH,clarithromycin(Clr),and p-aminosalicylic acid(PAS)with 3 cases each(6.3%).The top 7 drugs to which re-treated patients were resistant were INH with 10 cases(43.5%),Sm,RFP,and Rft with 8 cases each(34.8%),Rfb with 7 cases(30.4%),Pa and levofloxacin(Lfx)with 6 cases each(26.1%).The overall mono-resistance rate,poly-drug resistance rate,and multidrug-resistant rate to 16 anti-tuberculosis drugs were 9.9%,7.0%,and 11.3%,respectively;all mono-resistance patients were initially treated;there was no statistically significant difference in the poly-drug resistance rate between re-treated and initially treated patients(13.0%vs.4.2%,P=0.591),but the multidrug-resistant rate was significantly higher in re-treated patients(30.4%vs.2.1%,P=0.002).Conclusion Drug resistance in disseminated pulmonary tuberculosis is severe.Clinical physicians can develop personalized anti-tuberculosis treatment plans based on drug susceptibility test results.

Objective: To observe the clinical pathology features, and immune microenvironment of HER-2 intratumoral heterogeneity breast cancer. Methods: Thirty cases of HER-2 intratumoral heterogeneous breast cancer were retrospectively analyzed in Tianjin Medical University Cancer Institute and Hospital from November 2017 to June 2020. HER-2 expression was detected by immunohistochemistry and verified by dual color silver-enhanced in-situ hybridization (D-SISH). HER-2 intratumoral positive and negative regions were divided. The pathological characteristics, subtype, and the level of tumor infiltrating lymphocytes (TILs) and the expression of programmed cell death-ligand 1 (PD-L1) were evaluated respectively. Results: The proportion of HER-2 positive cells of the breast cancer ranged from 10% to 90%. The pathological type was mainly invasive non-special typecarcinoma. Six cases presented different pathological types between HER-2 positive and negative regions. The HER-2-positive areas included 2 cases of carcinoma with apocrine differentiation, and the negative areas included 2 cases of invasive micropapillary carcinoma, 1 case of invasive papillary carcinoma, and 1 case of carcinoma with apocrine differentiation. In HER-2 positive regions, 17 cases were Luminal B and 13 cases were HER-2 overexpressed types. There were 22 cases of Luminal B and 8 cases of triple negative tumors in the HER-2 negative areas. The levels of TILs in HER-2 positive and negative areas accounted for 53.3% (16/30) and 26.7% (8/30), respectively, with a statistically significant difference (P=0.035). The positive expression of PD-L1 in HER-2 positive area and HER-2 negative area were 6 cases and 9 cases, respectively. Among 8 cases with HER-2 negative regions containing triple negative components, 4 cases were positive for PD-L1 expression. Conclusions: In the case of HER-2 intratumoral heterogeneity, it is necessary to pay attention to both HER-2 positive and negative regions, and evaluate subtype separately as far as possible. For HER-2 intratumoral heterogeneous breast cancer containing triple negative components, the treatment mode can be optimized by refining the intratumoral expression of PD-L1.
Humans ; Female ; Breast Neoplasms/pathology* ; Retrospective Studies ; B7-H1 Antigen/metabolism* ; Lymphocytes, Tumor-Infiltrating/pathology* ; Carcinoma ; Tumor Microenvironment ; Triple Negative Breast Neoplasms/pathology* ; Prognosis ; Biomarkers, Tumor/metabolism*

Objective:To investigate the intervention effects and influencing factors of family management intervention on parents' disease management ability, family function of children with coronary artery lesions in Kawasaki disease.Methods:This was a quasi experimental study. Conveniently, 88 parents of children with Kawasaki disease coronary artery lesions from the Children's Hospital of Chongqing Medical University from March 2020 to June 2021 were selected for the study, and they were divided into the control group and the intervention group according to the order of the first consultation with 44 cases in each group. In the control group, conventional care and health education were used, while in the intervention group, a 6-month family management intervention was implemented on the basis of the control group. Family Management Measure (FaMM), Family Assessment Device (FAD) were used to assess the parents' disease management ability, family function before and after the intervention, respectively.Results:A total of 88 study subjects completed the pre-intervention survey in this study, and a total of 79 study subjects were surveyed when they returned to the hospital for review at the end of 6 months of intervention, including 40 in the intervention group and 39 in the control group, with a missed rate of 10.23% (9/88). There was no significant difference in the score of FAD, FaMM, Kawasaki disease knowledge questionnaire before the intervention between the two groups ( P>0.05). The scores of FAD in the intervention group was (21.58 ± 4.60) points, which was lower than that in the control group (24.62 ± 5.28) points, and the difference was statistically significant ( t=2.73, P <0.05). The scores of FaMM in the intervention group was (46.83 ± 6.02) points, which was higher than that in the control group (42.72 ± 6.09) points, and the differences was statistically significant ( t=-3.01, P <0.05). The age of the child, and whether the child was an only child were the influencing factors of the difference in disease management ability, and the difference in the family function of the parents of the child, respectively (all P<0.05). Conclusions:Family management intervention can improve the disease management ability of the parents of children with coronary artery lesion, improve family function. In the future, targeted interventions can be conducted according to different ages of children, and different family members' composition in order to obtain better intervention effects.

Objective: To investigate the mechanism of resveratrol promoting fibronectin type Ⅲ domain-containing 5 (FNDC5) degradation in skeletal muscle of male obese mice． Methods: Six-week-old male C57BL /6 mice were randomly divided into three groups : standard control diet ( SCD) ，high-fat diet ( HFD) and high-fat diet treated with resveratrol (HFD + RES) ．HFD + RES group was intervened with resveratrol via gavage ［400 mg / kg · d) ］ while fed HFD for 20 weeks．The body mass，serum TG，TC，LDL-C and HDL-C levels were detected．The pathological changes in skeletal muscle were detected by HE staining．The expression of FNDC5，SIRT1，SIRT2，LC3， p62，Beclin-1，ATG5，ATG7 was assessed by immunohistochemistry，RT-PCR and Western blot respectively. Results: The body mass ，serum TG ，TC and LDL-C levels increased significantly ，meanwhile HDL-C levels decreased in HFD group．Lipid deposition between skeletal muscle fibers were obvious in HFD group．The immuno- histochemistry results showed that protein expression levels of SIRT1，SIRT2 and LC3 obviously decreased，while the protein levels of FNDC5 and p62 obviously increased．The expression levels of FNDC5 significantly increased， while the gene expression levels of SIRT1，SIRT2，LC3，Atg7 and Beclin-1 obviously decreased．All these responses were attenuated by treatment with RES． Conclusion RES has obvious effects of lipid-lowering and promoting FNDC5 degradation in skeletal muscle tissues，which may be related with SIRT1 and SIRT2-induced autophagy， thus resulting in degradation of FNDC5 .