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.

Objective:To investigate and summarize pediatric patients with severe Mycoplasma pneumoniae pneumonia (MPP) presenting with varied clinical and chest imaging features in order to guide the individualized treatment. Methods:This was a retrospective cohort study. Medical records of clinical, imaging and laboratory data of 505 patients with MPP who were admitted to the Department Ⅱ of Respirology Center, Beijing Children′s Hospital, Capital Medical University from January 2016 to October 2023 and met the enrollment criteria were included. They were divided into severe group and non-severe group according to whether lower airway obliterans was developed. The clinical and chest imaging features of the two groups were analyzed. Those severe cases with single lobe ≥2/3 consolidation (lobar consolidation) were further divided into subtype lung-necrosis and subtype non-lung-necrosis based on whether lung necrosis was developed. Comparison on the clinical manifestations, bronchoscopic findings, whole blood C-reactive protein (CRP) and other inflammatory indicators between the two subtypes was performed. Comparisons between two groups were achieved using independent-sample t-test, nonparametric test or chi-square test. Univariate receiver operating characteristic (ROC) curve analyses were performed on the indicators such as CRP of the two subtypes. Results:Of the 505 cases, 254 were male and 251 were female. The age of the onset was (8.2±2.9) years. There were 233 severe cases, among whom 206 were with lobar consolidation and 27 with diffuse bronchiolitis. The other 272 belonged to non-severe cases, with patchy, cloudy infiltrations or single lobe <2/3 uneven consolidation or localized bronchiolitis. Of the 206 cases (88.4%) severe cases with lobar consolidation, 88 harbored subtype lung-necrosis and 118 harbored subtype non-lung-necrosis. All 206 cases (100.0%) presented with persistent high fever, among whom 203 cases (98.5%) presented with inflammatory secretion obstruction and plastic bronchitis under bronchoscopy. Of those 88 cases with subtype lung-necrosis, there were 42 cases (47.7%) with dyspnea and 39 cases (44.3%) with moderate to massive amount of pleural effusion. There were 35 cases (39.8%) diagnosed with lung embolism during the disease course, of which other 34 cases (38.6%) were highly suspected. Extensive airway mucosal necrosis was observed in 46 cases (52.3%), and the level of their whole blood CRP was significantly higher than that of subtype non-lung-necrosis (131.5 (91.0, 180.0) vs. 25.5 (12.0, 43.1) mg/L, U=334.00, P<0.001). They were regarded as subtype "lung consolidation-atelectasis-necrosis". Of those 118 cases with subtype non-lung-necrosis, 27 cases (22.9%) presented with dyspnea and none were with moderate to massive amount of pleural effusion. Sixty-five cases (55.1%) presented with plastic bronchitis and localized airway mucosal necrosis was observed in 32 cases (27.1%). They were deemed as subtype "lung consolidation-atelectasis". ROC curve analyses revealed that whole blood CRP of 67.5 mg/L on the 6-10 th day of disease course exhibited a sensitivity of 0.96, a specificity of 0.89, and an area under the curve of 0.97 for distinguishing between these two subtypes among those with lobar consolidation. Conclusions:Pediatric patients with severe MPP present with lobar consolidation or diffuse bronchiolitis on chest imaging. Those with lobar consolidation harbor 2 subtypes as "lung consolidation-atelectasis-necrosis" and "lung consolidation-atelectasis". Whole blood CRP of 67.5 mg/L can be applied as an early discriminating indicator to discriminate between these two subtypes.

Aim To prepare the sea cucumber enzy¬molysis fermentation liquid (SCEFL) by enzymatic hydrolysis of protease and fermentation of probiotics and to investigate the effect of SCEFL on the immunosup-pression induced by cyclophosphamide in mice and to explore its mechanism by metabomic method. Methods The immunosuppressive model was induced by in-traperitoneal injection of cyclophosphamide. C57BL/6J mice were randomly divided into normal group, model group, Levamisole group, SCEFL groups (at low, medium and high doses). The pathological changes of spleen were observed by HE staining. The proportion of CD4

Objective: To development the prognostic nomogram for malignant pleural mesothelioma (MPM). Methods: Two hundred and ten patients pathologically confirmed as MPM were enrolled in this retrospective study from 2007 to 2020 in the People's Hospital of Chuxiong Yi Autonomous Prefecture, the First and Third Affiliated Hospital of Kunming Medical University, and divided into training (n=112) and test (n=98) sets according to the admission time. The observation factors included demography, symptoms, history, clinical score and stage, blood cell and biochemistry, tumor markers, pathology and treatment. The Cox proportional risk model was used to analyze the prognostic factors of 112 patients in the training set. According to the results of multivariate Cox regression analysis, the prognostic prediction nomogram was established. C-Index and calibration curve were used to evaluate the model's discrimination and consistency in raining and test sets, respectively. Patients were stratified according to the median risk score of nomogram in the training set. Log rank test was performed to compare the survival differences between the high and low risk groups in the two sets. Results: The median overall survival (OS) of 210 MPM patients was 384 days (IQR=472 days), and the 6-month, 1-year, 2-year, and 3-year survival rates were 75.7%, 52.6%, 19.7%, and 13.0%, respectively. Cox multivariate regression analysis showed that residence (HR=2.127, 95% CI: 1.154-3.920), serum albumin (HR=1.583, 95% CI: 1.017-2.464), clinical stage (stage Ⅳ: HR=3.073, 95% CI: 1.366-6.910) and the chemotherapy (HR=0.476, 95% CI: 0.292-0.777) were independent prognostic factors for MPM patients. The C-index of the nomogram established based on the results of Cox multivariate regression analysis in the training and test sets were 0.662 and 0.613, respectively. Calibration curves for both the training and test sets showed moderate consistency between the predicted and actual survival probabilities of MPM patients at 6 months, 1 year, and 2 years. The low-risk group had better outcomes than the high-risk group in both training (P=0.001) and test (P=0.003) sets. Conclusion: The survival prediction nomogram established based on routine clinical indicators of MPM patients provides a reliable tool for prognostic prediction and risk stratification.
Humans ; Mesothelioma, Malignant ; Prognosis ; Nomograms ; Retrospective Studies ; Proportional Hazards Models

Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to investigate the metabolites of maackiain in rats based on the prediction function of UNIFI data processing system and liver microsomal incubation in vitro. Ten metabolites of maackiain after oral absorption were reasonably deduced and characterized. It was found that the biotransformation of maackiain mainly included phase Ⅰ oxidation, dehydrogenation, phase Ⅱ sulfate conjugation, glucosylation conjugation, and glucuronic acid conjugation. Among them, the product of glucosylation conjugation, trifolirhizin, was identified by comparison with the reference for the first time. Liver microsomal incubation in vitro further confirmed the metabolites and metabolic pathways of maackiain in rats. The metabolites in the blood, urine, and feces complemented each other, which revealed the migration, metabolism, and excretion modes of maackiain in rats. This study lays a foundation for the further investigation of the metabolic mechanism of maackiain in vivo and the in-depth research on the mechanism of pharmacodynamics and toxicity.
Animals ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Metabolic Networks and Pathways ; Pterocarpans ; Rats ; Rats, Sprague-Dawley

To evaluate whether the polygenic profile modifies the development of sporadic Alzheimer's disease (sAD) and pathological biomarkers in cerebrospinal fluid (CSF), 462 sAD patients and 463 age-matched cognitively normal (CN) controls were genotyped for 35 single-nucleotide polymorphisms (SNPs) that are significantly associated with sAD. Then, the alleles found to be associated with sAD were used to build polygenic risk score (PRS) models to represent the genetic risk. Receiver operating characteristic (ROC) analyses and the Cox proportional hazards model were used to evaluate the predictive value of PRS for the sAD risk and age at onset. We measured the CSF levels of Aβ42, Aβ42/Aβ40, total tau (T-tau), and phosphorylated tau (P-tau) in a subgroup (60 sAD and 200 CN participants), and analyzed their relationships with the PRSs. We found that 14 SNPs, including SNPs in the APOE, BIN1, CD33, EPHA1, SORL1, and TOMM40 genes, were associated with sAD risk in our cohort. The PRS models built with these SNPs showed potential for discriminating sAD patients from CN controls, and were able to predict the incidence rate of sAD and age at onset. Furthermore, the PRSs were correlated with the CSF levels of Aβ42, Aβ42/Aβ40, T-tau, and P-tau. Our study suggests that PRS models hold promise for assessing the genetic risk and development of AD. As genetic risk profiles vary among populations, large-scale genome-wide sequencing studies are urgently needed to identify the genetic risk loci of sAD in Chinese populations to build accurate PRS models for clinical practice.

BACKGROUND: Imprecise interpretation of coronary angiograms was reported and resulted in inappropriate revascularization. Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score is a comprehensive system to evaluate the complexity of the overall lesions. We hypothesized that a real-time SYNTAX score feedback from image analysts may rectify the mis-estimation and improve revascularization appropriateness in patients with stable coronary artery disease (CAD). METHODS: In this single-center, historical control study, patients with stable CAD with coronary lesion stenosis ≥50% were consecutively recruited. During the control period, SYNTAX scores were calculated by treating cardiologists. During the intervention period, SYNTAX scores were calculated by image analysts immediately after coronary angiography and were provided to cardiologists in real-time to aid decision-making. The primary outcome was revascularization deemed inappropriate by Chinese appropriate use criteria for coronary revascularization. RESULTS: A total of 3245 patients were enrolled and assigned to the control group (08/2016-03/2017, n = 1525) or the intervention group (03/2017-09/2017, n = 1720). For SYNTAX score tertiles, 17.9% patients were overestimated and 4.3% were underestimated by cardiologists in the control group. After adjustment, inappropriate revascularization significantly decreased in the intervention group compared with the control group (adjusted odds ratio [OR]: 0.83; 95% confidence interval [CI]: 0.73-0.95; P = 0.007). Both inappropriate percutaneous coronary intervention (adjusted OR: 0.82; 95% CI: 0.74-0.92; P < 0.001) and percutaneous coronary intervention utilization (adjusted OR: 0.88; 95% CI: 0.79-0.98; P = 0.016) decreased significantly in the intervention group. There was no significant difference in 1-year adverse cardiac events between the control group and the intervention group. CONCLUSIONS: Real-time SYNTAX score feedback significantly reduced inappropriate coronary revascularization in stable patients with CAD. CLINICAL TRIAL REGISTRATION Nos. NCT03068858 and NCT02880605; https://www.clinicaltrials.gov.

Objective: To explore the expression and regulatory function of sperm-associated antigen 6 (SPAG6) in the formation of the sperm acrosome in mice. METHODS: The expression of SPAG6 during the first wave of spermatogenesis on postnatal days (PN) 8, 12, 16, 20, 24, 28, 30 and 35 was examined by Western blot and the localization of SPAG6 in the testicular germ cells was determined by immunofluorescence. The expression plasmids of SPAG6 and serine protease inhibitor Kazal-type 2 (SPINK2) were constructed, the interaction between SPAG6 and SPINK2 in the AH109 and CHO cells examined by yeast two-hybrid and co-localization assays, and the expression and localization of SPINK2 in the testicular germ cells of the SPAG6-knockout (SPAG6 KO) mice detected by immunofluorescence. RESULTS: SPAG6 was highly expressed between PN 16 and 28 and localized in the acrosome of the round spermatids. Yeast two-hybrid assay showed the growth of SPAG6 and SPINK2 in the selective culture medium SD/-Leu/-Trp/-His, and the transfection of the CHO cells revealed the co-localization of SPAG6 and SPINK2 around the nuclei. The expression and acrosomal localization of SPINK2 were not found in the testicular germ cells of the SPAG6-KO mice. CONCLUSIONS SPAG6 interacts with SPINK2 and probably participates in the formation of the sperm acrosome by stabilizing the expression of SPINK2 during spermatogenesis.

Objective To study the clinicopathologic features,diagnosis and differential diagnosis of tumors of haematopoietic and lymphoid tissue in the female productive tract. Methods Eleven cases of myeloid sarcoma and leukemia, 9 of non Hodgkin lymphoma(NHL),13 of cervical lymphoma-like lesions were selected from Peking University People′s Hospital from January 2006 to August 2017. According to WHO classification of tumors of haematopoietic and lymphoid tissues(2008)and updated classification(2016),the cases were studied by microscopy,immunohistochemistry and in situ hybridization.Results In 20 cases of tumors of haematopoietic and lymphoid tissue,the mean and median age was 48.5 and 56 years old(range:16-77 years old).In cases of lymphoma-like lesion of uterine cervix,the mean and median age was 45.9 and 48 years old(range:23-62 years old).The patients with neoplasm present as fever,fatigue, hypogastralgia, colporrhagia and mass etc. Eight cases had history of acute myeloid leukemia, and 3 had myeloid leukemia while pregnancy. One case of chronic lymphocytic leukaemia/small lymphocytic lymphoma(CLL/SLL)had history of ovary small cell carcinoma and high grade serous carcinoma resected with chemotherapy.One case of diffuse large B cell lymphoma(DLBCL)had history of renal transplantation. Lactic dehydrogenase(LDH)was elevated in 9 cases(9/18).The cases of lymphoma-like lesion present as contact bleeding in most cases and all located in cervix. Four cases of neoplasm located in vulva, 1 in vagina,4 in cervix, 4 in uterine corpus, 8 in ovary and 2 in placenta.Clinical staging of NHL: 4 case was stageⅠ,1 case of stageⅢ,and 4 cases of stageⅣ.Pathological morphology:9 cases were myeloid sarcoma, 2 cases were placenta invaded by myeloid leukemia. Six cases were DLBCL, and 1 case was CLL/SLL, 1 case was mucosa associated lymphoid tissuse lymphoma(MALToma), and 1 case was anaplastic large cell lymphoma. Resected mass, chemotherapy was performed in tumors of haematopoietic and lymphoid tissue. Five cases of myeloid sarcoma and 2 of NHL died. In 13 cases of lymphoma-like lesion of uterine cervix, the general condition was good as following up. Conclusions The clinical history, pathological morphology and immunohistochemistry are very important for diagnosing tumors of haematopoietic and lymphoid tissue in the female productive tract.Resection with chemotherapy is recommended in treatment. The prognosis of lymphoma-like lesion of uterine cervix is good,and should be differentiated from lymphoma.

Application of a combination of various chromatographic techniques including column chromatography over silica gel, Sephadex LH-20, macroporous adsorbent resin, and reversed-phase HPLC, led to the isolation of 173 compounds including irdidoids, monoterpenes, sesquiterpenes, triterpenes, lignans, flavonoids, and simple aromatic derivatives from the ethyl acetate-soluble fraction of the whole plants of Valeriana jatamansi(Valerianaceae), and their structures were elucidated by spectroscopic methods including 1D, 2D NMR UV, IR, and MS techniques. Among them, 77 compounds were new. In previous reports, we have described the isolation, structure elucidation, and bioactivities of 68 new and 25 known compounds. As a consequence, we herein reported the isolation and structure elucidation of the remaining 9 new and 71 known compounds, the structure revision of valeriotriate A(8a), as well as cytotoxicity of some compounds.
Acetates ; Chromatography, High Pressure Liquid ; Flavonoids ; analysis ; Iridoids ; analysis ; Lignans ; analysis ; Molecular Structure ; Monoterpenes ; analysis ; Phytochemicals ; analysis ; Plant Extracts ; chemistry ; Sesquiterpenes ; analysis ; Triterpenes ; analysis ; Valerian ; chemistry