Objective To analyze the pathogenic characteristics of measles virus genotype D8 in three cases in Hubei Province. Methods An epidemiological investigation was conducted on three consecutive confirmed cases of measles in a city of Hubei Province within a week. Measles virus IgM antibody was detected by enzyme-linked immunosorbent assay, the measles virus nucleic acid was detected by real-time fluorescent quantitative polymerase chain, and the reverse transcription polymerase chain reaction was used to amplify the C-terminal 450-nucleotide sequence of the N gene. A phylogenetic tree of measles virus genotypes was constructed to compare the isolated strains with reference strains of measles from other regions, and the nucleotide homology and genotype were analyzed. Results The nucleotide homology of the N gene of three measles virus strains in Hubei Province in 2025 was 99.80%-100.00%, with one amino acid site difference. The N gene homology with the Swiss strain (MVs/Bern.CHE/19.23D8) and the Japanese strain (MVs/Tokyo.JPN/24.23/23124/D8) was 99.3% -99.7%, with one amino acid site difference. The nucleotide homology of N gene with the WHO D8 genotype reference strain (MVi/Manchester.GBR/30.94/D8) was 98.00%-98.20%, with six amino acid differences. The nucleotide homology of the N gene compared with the vaccine strain Shanghai-191 was 91.40%-91.60%, with 21 amino acid differences from the vaccine strain S191. Conclusion All the three measles virus strains in Hubei Province are of the genotype D8 and have a high homology. It is necessary to pay attention to imported cases of measles, and the etiological monitoring of measles virus should be continuously strengthened to provide a scientific basis for the elimination of measles.

ObjectiveTo investigate the effects of paeoniflorin （PF） on neuroinflammation and cognitive impairment in the rat model of Alzheimer's disease （AD） and to clarify whether its mechanism is associated with regulation of the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway. MethodsGlycosides related to AD-associated neuroinflammation were screened through bibliometric analysis， and the potential targets of PF were predicted through network pharmacology and molecular docking. A rat model of AD was established by intraperitoneal injection of D-galactose （100 mg·kg^-1·d^-1）. Rats were assigned into a control group， a model group， a PF （200 mg·kg^-1） group， and a donepezil （0.5 mg·kg^-1·d^-1） group， and drugs were administered by gavage for 21 days. The learning and memory abilities were evaluated by the Morris water maze （MWM）. Hematoxylin-eosin （HE） staining and Nissl staining were performed to observe hippocampal neuronal morphology. The mRNA levels of inflammatory factors were determined by Real-time quantitative polymerase chain reaction （Real-time PCR）， and the protein levels of molecules in the JAK2/STAT3 signaling pathway were determined by Western blot. ResultsCompared with the control group， the model group showed prolonged escape latency and decreased platform crossings and time spent in the target quadrant （P<0.05， P<0.01）， accompanied by increased expression of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）， as well as elevated ratios of phosphorylated （p）-JAK2/JAK2 and p-STAT3/STAT3 （P<0.01）. Compared with the model group， the PF group and donepezil group exhibited shortened escape latency and increased platform crossings and time spent in the target quadrant （P<0.05， P<0.01）， decreased expression levels of IL-1β and TNF-α， upregulated mRNA levels of interleukin-4 （IL-4） and interleukin-10 （IL-10）， and reduced ratios of p-JAK2/JAK2 and p-STAT3/STAT3 （P<0.05， P<0.01）. ConclusionPaeoniflorin can alleviate cognitive impairment and neuroinflammation in the rat model of AD by inhibiting the JAK2/STAT3 signaling pathway.

ObjectiveTo investigate the protective effect of Rehmanniae Radix iridoid glycosides （RIG） on the kidney tissue of streptozotocin （STZ）-induced diabetic mice and explore the underlying mechanism. MethodsTwelve of 72 male C57BL/6J mice were randomly selected as the normal group， and the remaining 60 mice were fed with a high-fat diet for six weeks combined with injection of 60 mg·kg^-1 STZ for 4 days to model type 2 diabetes mellitus. The successfully modeled mice were randomized into model， metformin （250 mg·kg^-1）， catalpol （100 mg·kg^-1）， low-dose RIG （RIG-L， 200 mg·kg^-1） and high-dose RIG （RIG-H， 400 mg·kg^-1） groups （n=11）. Mice in each group were administrated with corresponding drugs， while those in the normal group and model group were administrated with the same dose of distilled water by gavage once a day. After 8 weeks of intervention， an oral glucose tolerance test （OGTT） was performed， and the area under the curve （AUC） was calculated. After mice were sacrificed， both kidneys were collected. The body weight， kidney weight， and fasting blood glucose （FBG） were measured. Biochemical assays were performed to measure the serum levels of triglycerides （TG）， total cholesterol （TC）， serum creatinine （SCr）， and blood urea nitrogen （BUN）. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the serum level of fasting insulin （FINS）， and the insulin sensitivity index （ISI） and homeostatic model assessment for insulin resistance （HOMA-IR） were calculated. The pathological changes in kidneys of mice were observed by hematoxylin-eosin staining and Masson staining. The immunohistochemical method （IHC） was employed to assess the expression of interleukin-1 （IL-1）， interleukin-6 （IL-6）， tumor necrosis factor-α（TNF-α）， transforming growth factor-β₁ （TGF-β₁）， and collagen-3 （ColⅢ） in the kidney tissue. The protein levels of TGF-β₁， cell signal transduction molecule 3 （Smad3）， matrix metalloproteinase-9 （MMP-9）， and ColⅢ in kidneys of mice were determined by Western blot. ResultsCompared with the normal group， the model group showcased decreased body weight and ISI （P<0.01）， increased kidney weight， FBG， AUC， FINS， HOMA-IR， TC， TG， SCr， and BUN （P<0.01）， glomerular hypertrophy， capsular space narrowing， and collagen deposition in the kidney， up-regulated protein levels of IL-1， IL-6， TNF-α， TGF-β₁， ColⅢ， and Smad3 （P<0.01）， and down-regulated protein level of MMP-9 （P<0.01） in the kidney tissue. Compared with the model group， the treatment groups had no significant difference in the body weight and decreased kidney weight （P<0.05， P<0.01）. The FBG level declined in the RIG-H group after treatment for 4-8 weeks and in the metformin， catalpol， and RIG-L groups after treatment for 6-8 weeks （P<0.01）. The AUC in the RIG-L， RIG-H， and metformin groups decreased （P<0.05， P<0.01）. The levels of TC， SCr， and BUN in the serum of mice in each treatment group became lowered （P<0.05， P<0.01）. The level of TG declined in the RIG-L， RIG-H， and metformin groups （P<0.05， P<0.01）. The serum level of FINS declined in the catalpol， RIG-L， and metformin groups （P<0.01）. Compared with the model group， the treatment groups showed decreased HOMA-IR （P<0.01）， increased ISI （P<0.01）， alleviated pathological changes in the kidney tissue， and down-regulated expression of IL-1 and TGF-β₁. In addition， the protein levels of IL-6， TNF-α， and ColⅢ in the RIG-H and metformin groups and IL-6 and TNF-α in the RIG-L group were down-regulated （P<0.05， P<0.01）， and the protein levels of IL-6， TNF-α， and ColⅢ in the catalpol group and ColⅢ in the RIG-L group showed a decreasing trend without statistical difference. The protein levels of TGF-β₁， Smad3， and ColⅢ in the RIG-H and metformin groups were down-regulated （P<0.01）. Compared with that in the model group， the protein level of MMP-9 was up-regulated in each treatment group （P<0.01）. ConclusionRIG can improve the renal structure and function of diabetic mice by regulating the TGF-β₁/Smads signaling pathway.

Background and Aims:Centrally located breast cancer(CLBC),due to its proximity to the nipple-areolar complex,has long been treated primarily with mastectomy,while the oncologic safety of breast-conserving surgery(BCS)remains controversial.This study,based on a large-scale database combined with a real-world cohort,compared the survival outcomes of BCS and mastectomy to evaluate the feasibility and oncologic safety of BCS in CLBC patients.Methods:Data of 10 325 female CLBC patients diagnosed between 2010 and 2015 were extracted from the SEER database,including 5 601 patients who underwent BCS and 4 724 who underwent mastectomy.Propensity score matching(PSM)yielded 1 951 matched pairs,and disease-specific survival(DSS)and overall survival(OS)were compared between groups.Cox regression analyses were performed to identify prognostic factors,and subgroup analyses were conducted.Additionally,an independent validation cohort from Xiangya Hospital,Central South University(2015-2016)included 221 BCS and 636 mastectomy patients,with OS and progression-free survival(PFS)assessed.Results:After PSM,baseline characteristics between groups were well balanced.Kaplan-Meier analysis demonstrated no significant differences in DSS or OS between BCS and mastectomy,and 5-,7-,and 10-year OS rates were comparable(all P＞0.05).Subgroup analyses revealed equivalent outcomes for BCS and mastectomy in patients with T1/T2 disease,different HER2 statuses,and those receiving chemotherapy,while in patients receiving radiotherapy,BCS showed significantly better DSS and OS than mastectomy(both P＜0.05).Multivariate Cox regression identified T,N,and M stage,histologic grade,molecular subtype,ER/PR status,and chemotherapy as independent prognostic factors(all P＜0.05),whereas surgical type was not(P＞0.05).The validation cohort confirmed the SEER findings,with no significant differences in OS or PFS between the two groups(both P＞0.05).Conclusions:BCS provides DSS and OS comparable to mastectomy in CLBC patients and may confer additional survival benefits when combined with radiotherapy.These findings suggest that CLBC should not be considered a contraindication to BCS,supporting BCS as a feasible and safe surgical strategy that offers valuable evidence for individualized clinical decision-making and may help improve patients' quality of life.

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Objective To investigate the distribution of traditional Chinese medicine(TCM)syndromes in chronic persistent immunoglobulin A nephropathy(IgAN)and to explore the relationship between TCM syndromes and prognosis based on real-world research.Methods From January 2018 to January 2024,a total of 80 patients with chronic persistent IgAN who were admitted to Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University were included.The clinical baseline data and prognosis-related information were collected.The main outcome indicators were defined as renal failure events of glomerular filtration rate(eGFR)decreased by＞50%,serum creatinine doubled or end-stage renal disease(ESRD).The distribution of TCM syndromes in chronic persistent IgAN and the relationship between different deficiency syndromes and prognosis were preliminarily discussed.Results(1)Among the 80 patients with chronic persistent IgAN,the syndrome manifestations with an occurrence frequency of more than 30%in descending order were foamy urine(75.00%),fatigue and lassitude(71.25%),waist ache(61.25%),dry mouth(31.25%),lower extremity edema(31.25%),aversion to cold and cold limbs(30.00%),and insomnia(30.00%).(2)The commonly-seen root-deficiency syndrome in patients with chronic persistent IgAN was qi and yin deficiency syndrome,with a total of 28 cases(35.00%).And other root-deficiency syndromes were spleen and kidney yang deficiency syndrome in 22 cases(27.50%),lung and spleen qi deficiency syndrome in 15 cases(18.75%),and liver and kidney yin deficiency syndrome in 15 cases(18.75%).The commonly-seen complicated syndrome was water-damp syndrome,with a total of 17 cases(21.25%).The other complicated syndromes were damp-heat syndrome in 15 cases(18.75%),blood-stasis syndrome in 9 cases(11.25%),phlegm-damp syndrome in 7 cases(8.75%),turbidity-toxin syndrome in 5 cases(6.25%),liver depression syndrome in 3 cases(3.75%),and cold-damp syndrome in 1 case(1.25%).(3)Among the 80 patients with chronic persistent IgAN,21 cases(26.25%)had renal failure events,and their syndrome types were lung and spleen qi deficiency syndrome in 9 cases(60.00%),qi and yin deficiency syndrome in 3 cases(10.71%),liver and kidney yin deficiency syndrome in 3 cases(20.00%),and spleen and kidney yang deficiency syndrome in 6 cases(27.27%).The incidence of renal failure events in patients with lung and spleen qi deficiency syndrome was significantly higher than that in the other three syndrome types,and the chi-square test showed that the difference was statistically significant(P＜0.05).(4)Kaplan-Meier survival analysis showed that the cumulative incidence of 2-year and 5-year endpoint events in patients with lung and spleen qi deficiency syndrome was 23.10%and 46.20%,respectively,and the final incidence was 85.00%.The cumulative incidence of 2-year and 5-year endpoint events in patients with other deficiency syndromes was 4.50%and 19.70%,respectively,and the final incidence was 71.60%.The intergroup comparison(tested by Log-rank)showed that the incidence of renal failure events in patients with lung and spleen qi deficiency syndrome was significantly higher than that in patients with other root-deficiency syndromes,and the difference was statistically significant(P＜0.05).(5)COX proportional hazard regression analysis showed that lung and spleen qi deficiency syndrome(HR=7.755,95%CI 1.631-36.874,P＜0.05)and anemia(HR=8.205,95%CI 1.007-66.857,P＜0.05)were the independent risk factors for renal failure events in patients with chronic persistent IgAN.Conclusion Qi and yin deficiency syndrome is the most common syndrome in the patients with chronic persistent IgAN,and lung and spleen qi deficiency syndrome and anemia are the independent risk factors for renal failure events in IgAN.

Milk-derived exosomes are nanoscale extracellular vesicles naturally present in mammalian milk and are rich in proteins,lipids,nucleic acids,and bioactive metabolites.They exhibit biological activities such as anti-inflammatory,antioxidant,and immunomodulatory effects.Owing to their unique advantages of low immunogenicity,excellent biocompatibility,stability,and natural targeting ability,milk-derived exosomes have emerged as promising natural nanocarriers,garnering significant attention in disease treatment and nutritional interventions.Sarcopenia,characterized by reduced skeletal muscle mass and diminished strength,is closely associated with aging,chronic inflammation,and oxidative stress.Recent studies have highlighted the potential role of milk-derived exosomes in combating sarcopenia.These exosomes can increase myotube diameter,enhance muscle mass and fiber cross-sectional area,and improve exercise performance metrics such as grip strength.Potential mechanisms may include promoting muscle anabolism,improving mitochondrial function through antioxidant mechanisms,and modulating the inflammatory microenvironments.However,challenges remain in their application for sarcopenia at present,such as the unclear mechanisms of key bioactive components[e.g.,microRNAs(miRNAs),L-ornithine,and milk fat globule-epidermal growth factor 8(MFG-E8)],and the targeting and stability of delivery systems need to be optimized.Future research should focus on the functional analysis of components in exosomes,optimization of delivery systems,and preclinical validation to promote their practical application in managing age-related muscle health.

Objective:To analyze the clinical features and genetic sequencing results of a patient with Kallmann syndrome(KS) carrying digenic mutations who initially presented with osteoporosis, and to enhance awareness of this disease phenotype.Methods:Clinical data were collected, and peripheral blood DNA was extracted for whole-exome sequencing. Relevant literature was reviewed to summarize phenotypes associated with digenic/oligogenic variants involving CHD7.Results:The patient exhibited back pain, delayed development of secondary sexual characteristics, and hyposmia. Laboratory tests revealed reduced sex hormones and gonadotropin levels, while pituitary imaging was unremarkable. Bone mineral density imaging confirmed osteoporosis, and thoracolumbar X-rays showed multiple vertebral compression fractures. Genetic analysis identified a heterozygous splice-site mutation in CHD7(c.2698-1G>T) and a heterozygous missense mutation in WDR11(c.439G>A: p.D147N). According to ACMG criteria, the CHD7 mutation was classified as pathogenic, while the WDR11 variant was defined as a variant of uncertain significance(VUS). Literature review indicated that 40% of KS patients with digenic/oligogenic variants involving CHD7 presented with hearing or ocular abnormalities.Conclusion:This study reports a novel CHD7 mutation and a previously undescribed digenic combination of CHD7 and WDR11 variants in a KS patient. CHD7 variants may be implicated in auditory or ocular involvement in KS cases with digenic/oligogenic inheritances. KS patients may also manifest skeletal abnormalities in addition to hypogonadotropic hypogonadism. Tailored management of sex hormones and osteoporosis therapies across life stages is essential for optimizing bone health in KS.

As the incidence of autism rises annually,its unknown pathogenesis makes it challenging to treat the varied repetitive and stereotyped behaviors that characterize its core symptoms.The striatum is an important brain region for the control of locomotor behaviors,featuring a unique mosaic structure,complex neural origin,and finely regulated developmental process that is highly susceptible to genetic and environmental influences.Both clinical and basic studies have indicated that abnormal development of the striatal nuclei may contribute to the pathogenesis of these repetitive stereotyped behaviors in autism.Clinical imaging data have primarily identified gross anatomical variations in the stratum(e.g.,its general outline),but lack the resolution necessary to detect the cellular and subcellular alterations within the region.By introducing the abnormalities in the spatiotemporal development of the striatum and their links to the characteristic behaviors of autism,this review aims to advance our understanding of the role of the striatum in autism pathogenesis and to inform future animal studies and clinical research.

Objective:To observe the effects of palmitic acid(PA)and static pressure on the expression of receptor activator of NF-κB ligand(RANKL)and osteoprotegerin(OPG)in human periodontal ligament cells(HPDLCs)cultured from the subjects of differ-ent ages.Methods:The effects of PA with the dose(μmol/L)of 10,100,200,250,300,400 and 500 respectively on the prolif-erative activity of HPDLCs cultured in vitro from the subjects aged 12-45 years were determined by CCK-8 method.200 μmol/L PA was selected to treat HPDLCs,and the static pressure of 200 Pa was applied in the in vitro culture.Under different conditions(PA group,static pressure group,PA+static pressure group and blank control group),The expression of RANKL and OPG in HPDLCs was determined by ELISA before and after the treatment at 3,6,12,24,36,48 and 72 h respectively,and the OPG/RANKL ratio was calculated.Results:PA inhibited the proliferation of HPDLCs of all ages(P＜0.05),and the proliferation activity of HPDLCs decreased gradually with the increase of PA concentration,patient age and treatment time.Under static pressure,PA up-regulated the expression of RANKL protein,down-regulated the expression of OPG protein and the ratio of OPG/RANKL(P＜0.05),but RANKL protein expression decreased and OPG protein expression and the ratio of OPG/RANKL increased with age.Conclusion:Combined treatment of PA and static pressure can synergistically promote remodeling of periodontal bone.The expressions of RANKL and OPG is closely related to age of the subjects.