Objective To compare the clinical characteristics of pneumococcal meningitis in different age groups, and to provide a basis for early diagnosis of pneumococcal meningitis. Methods Cerebrospinal fluid and/or serum samples were collected from 1742 suspected cases of meningitis in Baoji, Shaanxi Province from August 2013 to July 2019. Streptococcus pneumoniae was detected by isolation culture and real-time fluorescence quantitative polymerase chain reaction. Retrospective analysis of clinical manifestations, biochemical indicators and other information of laboratory confirmed cases was conducted by χ² test or Fisher's exact test. Results A total of 1742 samples of encephalitis or meningitis cases were detected, and 41 cases were confirmed as laboratory-confirmed Streptococcus pneumoniae infection. Among them, there were 12 cases (29.27%) in the infant group, 14 cases (34.15%) in the child group, and 15 cases (36.59%) in the adult group. The proportion of the adults with headache was significantly higher than that of the infants (χ²=11.408，P＜0.017). The proportion of the adults with consciousness disorder, elevated white blood cells and elevated neutrophils were significantly higher than those in the infant and the child groups（Fisher's exact test, P＜0.017；χ² =6.428，P＜0.017；χ² =10.898，P＜0.017；χ² =6.421，P＜0.017；χ² =9.758，P＜0.017；χ² =7.744，P＜0.017). The proportion of the infants with cerebrospinal fluid turbidity was significantly higher than that of the children (Fisher's exact test，P＜0.017). The proportion of the infants with decreased white blood cells and reduced glucose in cerebrospinal fluid was significantly higher than that of the children group and the adult group（Fisher's exact test, P＜0.001；Fisher's exact test, P＜0.001；Fisher's exact test, P＜0.017; Fisher's exact test, P＜0.017). Conclusion Most adult patients with pneumococcal meningitis have headache and consciousness disorders, with significantly increased proportion of white blood cells and neutrophils. Infant patients tend to have cloudy appearance of cerebrospinal fluid, leukopenia in blood, and decreased glucose in cerebrospinal fluid.

ObjectiveAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties with communication and social interaction, restricted and repetitive behaviors. Previous studies have indicated that individuals with ASD exhibit early and lifelong attention deficits, which are closely related to the core symptoms of ASD. Basic visual attention processes may provide a critical foundation for their social communication and interaction abilities. Therefore, this study explores the behavior of children with ASD in capturing attention to changes in topological properties. MethodsOur study recruited twenty-seven ASD children diagnosed by professional clinicians according to DSM-5 and twenty-eight typically developing (TD) age-matched controls. In an attention capture task, we recorded the saccadic behaviors of children with ASD and TD in response to topological change (TC) and non-topological change (nTC) stimuli. Saccadic reaction time (SRT), visual search time (VS), and first fixation dwell time (FFDT) were used as indicators of attentional bias. Pearson correlation tests between the clinical assessment scales and attentional bias were conducted. ResultsThis study found that TD children had significantly faster SRT (P<0.05) and VS (P<0.05) for the TC stimuli compared to the nTC stimuli, while the children with ASD did not exhibit significant differences in either measure (P>0.05). Additionally, ASD children demonstrated significantly less attention towards the TC targets (measured by FFDT), in comparison to TD children (P<0.05). Furthermore, ASD children exhibited a significant negative linear correlation between their attentional bias (measured by VS) and their scores on the compulsive subscale (P<0.05). ConclusionThe results suggest that children with ASD have difficulty shifting their attention to objects with topological changes during change detection. This atypical attention may affect the child’s cognitive and behavioral development, thereby impacting their social communication and interaction. In sum, our findings indicate that difficulties in attentional capture by TC may be a key feature of ASD.

Guided by the theory of "the kidney storing essence, governing the bones, and producing marrow", this study explored the mechanism of icariin(ICA) in regulating the osteogenic differentiation of rat bone mesenchymal stem cells(BMSCs) through caveolin-1(Cav1) via in vitro and in vivo experiments, aiming to provide a theoretical basis for the prevention and treatment of postmenopausal osteoporosis with traditional Chinese medicine(TCM). Primary cells were obtained from 4-week-old female SD rats using the whole bone marrow adherent method. Flow cytometry was used to detect the expression of surface markers CD29, CD90, CD11b, and CD45. The potential for osteogenic and adipogenic differentiation was assessed. The effect of ICA on cell viability was determined using the CCK-8 assay, and the impact of ICA on the formation of mineralized nodules was verified by alizarin red staining. A stable Cav1-silenced cell line was constructed using lentivirus. The effect of Cav1 silencing on osteogenic differentiation was observed via alizarin red staining. Western blot analysis was conducted to detect the expression of Cav1, Hippo/TAZ, and osteogenic markers such as Runt-related transcription factor 2(RUNX2) and alkaline phosphatase(ALP). The results showed that primary cells were successfully obtained using the whole bone marrow adherent method, positively expressing surface markers of rat BMSCs and possessing the potential for both osteogenic and adipogenic differentiation. The CCK-8 assay and alizarin red staining results indicated that 1×10~(-7) mol·L~(-1) was the optimal concentration of ICA for intervention in this experiment(P<0.05). During osteogenic induction, ICA inhibited Cav1 expression(P<0.05) while promoting TAZ expression(P<0.05). Alizarin red staining demonstrated that Cav1 silencing significantly promoted the osteogenic differentiation of BMSCs. After ICA intervention, TAZ expression was activated, and the expression of osteogenic markers ALP and RUNX2 was increased. In conclusion, Cav1 silencing significantly promotes the osteogenic differentiation of BMSCs, and ICA promotes this differentiation by inhibiting Cav1 and regulating the Hippo/TAZ signaling pathway.
Animals ; Mesenchymal Stem Cells/metabolism* ; Caveolin 1/genetics* ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; Cell Differentiation/drug effects* ; Female ; Signal Transduction/drug effects* ; Flavonoids/administration & dosage* ; Protein Serine-Threonine Kinases/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Cells, Cultured ; Humans

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

Objective To construct an aptamer-functionalized carboxylated graphene oxide(CGO)fluo-rescent sensor to achieve highly sensitive and specific detection of ketamine(KET)and its metabolite norketamine(NK)using an aptamer capable of simultaneously recognizing KET and NK.Methods A specific aptamer for simultaneous recognition of KET and NK was screened using graphene oxide-sys-tematic evolution of ligand by exponential enrichment(GO-SELEX)and molecular docking tech-niques.The aptamer,labeled with Cy5 fluorescence,was chemically conjugated to CGO to construct an aptamer-functionalized CGO fluorescent sensor.By optimizing detection conditions,including the mass concentration of CGO,aptamer concentration,reaction temperature,and incubation time,quantita-tive analysis of the target analytes was achieved using the ratio of fluorescence intensity changes be-fore and after target addition.The stability of the sensor in biological matrices was evaluated by moni-toring fluorescence intensity changes over incubation time in blank blood and urine,in comparison with the traditional physical adsorption-based CGO fluorescent sensor.Spiked recovery experiments in blank blood and urine were conducted to compare performance with that of HPLC-MS/MS.Results A specific aptamer A5 was selected and chemically conjugated with CGO to construct the aptamer-functionalized CGO fluorescent sensor.Under optimized conditions,the proposed fluorescent sensor ex-hibited a linear detection range of 1.0-5.0 ng/mL for KET,with a limit of detection(LOD)of 0.86 ng/mL;while for NK,the linear detection range was 1.0-5.0 ng/mL,with an LOD of 0.70 ng/mL.Com-pared with the CGO fluorescent sensor constructed via physical adsorption,this sensor demonstrated greater stability in blood and urine.The spiked recovery rates of KET and NK in blank blood and urine ranged from 81.50%to 110.03%,exhibiting detection performance comparable to that of HPLC-MS/MS.Conclusion The aptamer screening method offers a novel approach for selecting aptamers tar-geting drugs and their metabolites.The constructed aptamer-functionalized CGO fluorescent sensor pro-vides an efficient and reliable strategy for the high-performance detection of KET and NK.

Objective To explore the correlation between the rs7296288 single nucleotide polymorphism(SNP)of the DHH gene and the onset of depression.Methods From March 2018 to December 2019,480 patients with depression in Sichuan Provincial People's Hospital,Jining Mental Hospital,Yunnan Mental Health Center were collected as the case group,and 329 patients without depression were collected as the control group.Peripheral blood samples were collected and DNA was extracted.After multiple amplification and high-throughput sequencing,statistical software was used to analyze the relevant data.Results The rs7296288 polymorphism of the DHH gene,the AA genotype was 32.9％in the control group and 36.7％in the case group,with no statistical difference;the AC genotype was 52.8％in the control group and 47.7％in the case group,with no statistical difference;the CC genotype was 14.3％in the control group and 15.6％in the case group,with no statistical difference.The co-dominant,dominant,and recessive statistical models were not statistically significant.Subgroup analysis of the degree of depressive episodes,suicide attempts,and first-episode patients did not find an association between the rs7296288 SNP locus of the DHH gene and the clinical features of depression,that is,the SNP rs7296288 of the DHH gene had no significant correlation with depression.Conclusion The rs7296288 polymorphism of DHH gene is not correlated with the pathogenesis of depression.

ObjectiveThe traditional Chinese medicine Strychnos nux-vomica L. (SN) has the clinical effect of reducing swelling and relieving pain; however, SN is toxic due to its alkaloid components. Little is known about the endogenous metabolic changes induced by SN toxicity in rats and their potential effects on the metabolic dysregulation of intestinal microbiota. Therefore, toxicological investigation of SN is of great significance to its safety assessment. In this study, the toxic mechanisms of SN were explored using a combination of metabonomics and 16S rRNA gene sequencing. MethodsThe toxic dose, intensity, and target organ of SN were determined in rats using acute, cumulative, and subacute toxicity tests. UHPLC-MS was used to analyze the serum, liver, and renal samples of rats after intragastric SN administration. The decision tree and K Nearest Neighbor (KNN) model were established based on the bootstrap aggregation (bagging) algorithm to classify the omics data. After samples were extracted from rat feces, the high-throughput sequencing platform was used to analyze the 16S rRNA V3-V4 region of bacteria. ResultsThe bagging algorithm improved the accuracy of sample classification. Twelve biomarkers were identified, where their metabolic dysregulation may be responsible for SN toxicity in vivo. Several types of bacteria such as Bacteroidetes, Anaerostipes, Oscillospira and Bilophila, were demonstrated to be closely related to physiological indices of renal and liver function, indicating that SN-induced liver and kidney damage may be related to the disturbance of these intestinal bacteria. ConclusionThe toxicity mechanism of SN was revealed in vivo, which provides a scientific basis for the safe and rational clinical use of SN.

Objective:The expression of serum free light chain(FLC)is abnormal in various diseases,but its role in lung cancer remains unclear.This study aims to investigate the expression and diagnostic value of serum FLC in lung cancer. Methods:A total of 80 lung cancer patients treated at Xiangdong Hospital,Hunan Normal University from January to December 2021 were selected as the lung cancer group.Another 80 healthy individuals undergoing routine physical examinations during the same period were chosen as the control group.General information and serum κFLC and λFLC levels were collected for all subjects.Clinical indicators such as serum carcinoembryonic antigen(CEA),cytokeratin fragment antigen 21-1(CYFRA21-1)levels,tumor diameter,histological type,TNM stage,and lymph node metastasis status were recorded for lung cancer patients.The expression levels of serum FLC[κFLC,λFLC,and FLC(κ+λ)]were compared between the lung cancer group and the control group.Lung cancer patients were grouped based on gender,age,smoking history,tumor diameter,TNM stage,histological type,and lymph node metastasis to compare differences in serum κFLC and λFLC levels.Receiver operating characteristic(ROC)curves were used to evaluate the diagnostic value of serum FLC alone and in combination with other indicators in lung cancer. Results:The expression levels of serum FLC(κ+λ)and κFLC were significantly higher in the lung cancer group than those in the control group(both P＜0.001),while there was no significant difference in serum λFLC levels between the 2 groups(P＞0.05).There were no significant differences in serum κFLC levels among lung cancer patients with different tumor diameters,histological types,or TNM stages(all P＞0.05);however,serum κFLC levels were higher in lung cancer patients with lymph node metastasis than in those without,with statistical significance(P=0.033).There were no significant differences in serum λFLC levels based on tumor diameter or histological type(both P＞0.05),but serumλFLC levels were higher in stage Ⅲ+Ⅳ and lymph node metastatic lung cancer patients compared to stage Ⅰ+Ⅱ and non-metastatic patients,with statistical significance(P=0.033 and P=0.019,respectively).The area under the curve(AUC)for κFLC and CEA in diagnosing lung cancer showed no significant difference(P=0.333).The combination ofκFLC+CYFRA21-1 had the highest diagnostic efficacy(AUC=0.875)and sensitivity(71.3％).The AUC for the combined diagnosis of κFLC+λFLC+CEA+CYFRA21-1 was 0.915(95％CI 0.860 to 0.953,P＜0.001). Conclusion:Serum FLC is highly expressed in lung cancer and is associated with its invasion and metastasis.Serum FLC,particularly κFLC,has diagnostic value for lung cancer,and the combined detection of FLC,CEA,and CYFRA21-1 offers the best diagnostic efficacy.

Objective To explore the possible effects and the underlying molecular mechanisms of xueshuantong[The main active component is panax notoginseng(PNS)]on the cognitive function and neural excitability of mice with Alzheimer's disease(AD).Methods The APP/PS1 mice were used as an animal model for AD research,at the stage when amyloid protein was not detected in mice(2 months of age).Mice in the xueshuantong group(APP/PS1+PNS)were administered by gavage once a day at a dose of 60 mg/kg for six months(for 8 months of age).The mice of the control group were given 0.9%sodium chloride(APP/PS1+Vehicle)intragastric treatment of the same volume,while the wild-type mice of the same age were given 0.9%sodium chloride intragastric treatment as the normal control group(WT+Vehicle)(15 mice in each group,n=15).After six months,the cognitive function of the mice was evaluated by the Novel Object Recognition(NOR)task and Morris Water Maze(MWM)test.The activity of BACE1,the distribution and expression of Nav1.1α,as well as the expression and enzymatic hydrolysis of Navβ2(Navβ2 full-length and Navβ2-CTF fragments)in cortex and hippocampus were detected by EEG,Western blot and cell surface biotinylation assay,respectively.Results The NOR task showed that compared with the mice in the APP/PS1+Vehicle group,the Discrimination index(DI)of mice in the APP/PS1 group was significantly increased after xueshuantong administration(P<0.05).The MWM test found that,the escape latency of the mice in the xueshuantong group was shortened followed six months in gastric administration(P<0.05),while the stay time in the target quadrant and the number of platforms significantly increased(P<0.05)after the removal of the platform.The results of EEG recording showed that xueshuantong reduced the frequency of spike-wave discharges in APP/PS1 mice(P<0.05).Furthermore,xueshuantong significantly reduced the expression of BACE1(P<0.05).In the APP+PNS group,the expression of Navβ2 full-length was increased(P<0.05),as well as corrected the abnormal distribution of Nav1.1α inside and outside of neurons(P<0.05).Conclusion Treatment with xueshuantong can significantly improve the learning and memory ability and correct the abnormal excitability of the brain in AD model mice.The mechanism may be related to the inhibition of BACE1 activity,the reduction of APP/PS1-induced excessive enzyme digestion of Navβ2,the correction of the abnormal expression and distribution of Nav1.1α in cortical and hippocampal neurons,as well as the subsequent regulation of neuronal excitability.

The biological clock(also known as the circadian rhythm)is the fundamental reliance for all organisms on Earth to adapt and survive in the Earth's rotation environment.Circadian rhythm is the most basic regulatory mechanism of life activities,and plays a key role in maintaining normal physiological and biochemical homeostasis,disease occurrence and treatment.Recent studies have shown that the biologi-cal clock plays an important role in the development of oral tissues and in the occurrence and treatment of oral diseases.Since there is cur-rently no guiding literature on the research methods of biological clock in stomatology,researchers mainly conduct research based on pub-lished references,which has led to controversy about the research methods of biological clock in stomatology,and there are many confusions about how to rationally apply the research methods of circadia rhythms.In view of this,this expert consensus summarizes the characteristics of the biological clock and analyzes the shortcomings of the current biological clock research in stomatology,and organizes relevant experts to summarize and recommend 10 principles as a reference for the rational implementation of the biological clock in stomatology research.