Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that severely affects the health of the elderly, marked by its incurability, high prevalence, and extended latency period. The current approach to AD prevention and treatment emphasizes early detection and intervention, particularly during the pre-AD stage of mild cognitive impairment (MCI), which provides an optimal “window of opportunity” for intervention. Clinical detection methods for MCI, such as cerebrospinal fluid monitoring, genetic testing, and imaging diagnostics, are invasive and costly, limiting their broad clinical application. Speech, as a vital cognitive output, offers a new perspective and tool for computer-assisted analysis and screening of cognitive decline. This is because elderly individuals with cognitive decline exhibit distinct characteristics in semantic and audio information, such as reduced lexical richness, decreased speech coherence and conciseness, and declines in speech rate, voice rhythm, and hesitation rates. The objective presence of these semantic and audio characteristics lays the groundwork for computer-based screening of cognitive decline. Speech information is primarily sourced from databases or collected through tasks involving spontaneous speech, semantic fluency, and reading, followed by analysis using computer models. Spontaneous language tasks include dialogues/interviews, event descriptions, narrative recall, and picture descriptions. Semantic fluency tasks assess controlled retrieval of vocabulary items, requiring participants to extract information at the word level during lexical search. Reading tasks involve participants reading a passage aloud. Summarizing past research, the speech characteristics of the elderly can be divided into two major categories: semantic information and audio information. Semantic information focuses on the meaning of speech across different tasks, highlighting differences in vocabulary and text content in cognitive impairment. Overall, discourse pragmatic disorders in AD can be studied along three dimensions: cohesion, coherence, and conciseness. Cohesion mainly examines the use of vocabulary by participants, with a reduction in the use of nouns, pronouns, verbs, and adjectives in AD patients. Coherence assesses the ability of participants to maintain topics, with a decrease in the number of subordinate clauses in AD patients. Conciseness evaluates the information density of participants, with AD patients producing shorter texts with less information compared to normal elderly individuals. Audio information focuses on acoustic features that are difficult for the human ear to detect. There is a significant degradation in temporal parameters in the later stages of cognitive impairment; AD patients require more time to read the same paragraph, have longer vocalization times, and produce more pauses or silent parts in their spontaneous speech signals compared to normal individuals. Researchers have extracted audio and speech features, developing independent systems for each set of features, achieving an accuracy rate of 82% for both, which increases to 86% when both types of features are combined, demonstrating the advantage of integrating audio and speech information. Currently, deep learning and machine learning are the main methods used for information analysis. The overall diagnostic accuracy rate for AD exceeds 80%, and the diagnostic accuracy rate for MCI also exceeds 80%, indicating significant potential. Deep learning techniques require substantial data support, necessitating future expansion of database scale and continuous algorithm upgrades to transition from laboratory research to practical product implementation.

Schizophrenia is a serious mental disease. The diagnosis of schizophrenia so far relies heavily on subjective evidence, including self-reported experiences by patients, manifestations described by relatives, and abnormal behaviors assessed by psychiatrists. The diagnosis, monitoring of the disease progression and therapy efficacy assessment are challenging due to the lack of established laboratory biomarkers. Based on the current literature, clinical consensus, guidelines, and expert recommendations, this review highlighted evidence-based potential laboratory biomarkers for the diagnosis of schizophrenia, including genetic biomarkers, neurotransmitters, neurodevelopmental-related proteins, and intestinal flora, and discussed the potential future directions for the application of these biomarkers in this field, aiming to provide an objective basis for the use of these biomarkers in the early and accurate diagnosis, treatment, and prognosis and rehabilitation assessment of schizophrenia.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Aim To investigate whether endoplasmic reticulum stress is involved in the neurotoxicity of sodi¬um arsenite and clarify whether over-expression of 3-mercaptopyruvate sulfurtransferase (MPST) regulates endoplasmic reticulum stress induced by arsenic. Methods The SH-SY5Y cell line stably expressing the exogenous MPST gene was obtained by constructing the lentiviral vector of MPST gene. The SH-SY5Y cells were randomly divided into six groups, the SR-MPST over-expression group stably expressing the exogenous MPST gene, SH-PEB control group transfected with empty vector, the arsenite treatment group ( NaAs02 group ), TUDC A treatment group ( blocker of endoplasmic reticulum stress ) and TUDC A + NaAs02 group. Western blot was used to examine the protein expression of GRP78 and CHOP after different treatment. Results Although MPST overexpression had no significant effects on the expression of GRP78 and CHOP proteins, NaAs02 could significantly increased the protein levels of GRP78 and CHOP ( P < 0. 01 ) and the up-regulation of GRP78 and CHOP proteins caused by NaAs02 could be blocked by the treatment of TUDC A. In addition, the inhibition by MPST overexpression on the arsenic-induced increase of GRP78 and CHOP proteins (P <0. 01 ) could also be reversed by the TUDC A treatment significantly. Conclusions The GRP78/ CHOP endoplasmic reticulum stress pathway is involved in the neurotoxic damage induced by arsenic; MPST overexpression may decrease arsenic-induced endoplasmic reticulum stress.

An ultra performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method was developed for the determination of 11 kinds of aminoglycosides (AGs), including paromomycin, spectinomycin, tobramycin, gentamycin, kanamycin, hygromycin B, apramycin, streptomycin, dihydrostreptomycin,amikacin and neomycin in aquatic products. Samples were extracted by phosphate buffer solution, and purified on molecularly imprinted polymers (MIP) solid phase extraction column. After separated by Obelisc R chromatographic column, AGs were detected by UPLC-MS/MS. It showed a good linearity relationship in the AGs concentration range of 1.0-1000 ng/mL with the correlation coefficient R2>0.994. The limit of detection (LOD,S/N≥3) was ranged from 1.0 μg/kg to 10.0 μg/kg,and the limit of quantitation (LOQ,S/N≥10) was ranged from 2.0 μg/kg to 20.0 μg/kg. Besides, the average recoveries presented 78.4%-109.6% with the relative standard deviation (RSD, n=6) of 2.3%-14.9%. This method was successfully applied to the simultaneous determination of 11 kinds of AGs with high sensitivity in aquatic products.

AIM:To investigate the clinical characteristics of microRNA(miR)-196b in colorectal cancer(CRC)and to study its biological function in 5-fluorouracil(5-FU)resistance.METHODS:miRNA sequence dataset and the corresponding clinical data of CRC patients were downloaded from The Cancer Genome Atlas(TCGA).Expression level and clinical characteristics of miR-196b in CRC patients were analyzed using SPSS 17.0.CRC cell line overexpres-sing miR-196b was established using transient transfection method.MTS test was used to evaluate the effect of miR-196b overexpression on 5-FU resistance.RESULTS:miR-196b expression was associated with lymph node metastasis and TNM stage(P<0.05),but not related with age and sex.Lymph node metastasis and distant metastasis were independent prog-nostic factors for rectal patients(P<0.05).The expression level of miR-196b was not associated with survival condition of rectal patients.The viability of the cells overexpressing miR-196b treated with different concentrations of 5-FU was signifi-cantly higher than that in control group(P<0.05).CONCLUSION:miR-196b may be a potential biomarker of TNM stage and lymph node metastasis in CRC.miR-196b increases the 5-FU resistance of CRC cells.

OBJECTIVETo investigate the effect of myeloma-derived exosomes on surface activating receptors of NK cells, and to explore the mechanism of the function defect of NK cells.

METHODSThe exosomes from the supernatant of multiple myeloma cell lines RPMI8226 and U266 were extracted by ultracentrifugation, and the size of them was identified under electron microscope; the human primary NK cells were extracted, and were co-cultured with the myeloma-derived exosomes (40 µg/ml), then the expression levels of surface activating receptors NKp46, NKp30 and NKG2D of NK cells at 0,1,4 and 24 hours were detected by flow cytometry.

RESULTSThe exosomes showed small vesicular, sized 30-100 nm under electron microscope. The expression of surface activating receptors of NK cells declined at different degree after co-cultured with myeloma-derived exosomes.

CONCLUSIONMyeloma-derived exosomes can inhibit the expression of surface activating receptors of NK cells.

Objective To investigate the surgical reparation of large coloboma raw surface after facial tumour resection in elderly patients.Methods According to the position and characteristics of tumor as well as the age and tolerance of the patients, full thick skin graft, the skin flaps with subcutaneous pedicle and free skin flap were designed and used in the reparation.Results 24 cases with large coloboma raw surface (5 cm×7 cm-12 cm× 16 cm)were treated by the utilization of three approaches after tumor resection.The large coloboma raw surface in all patients achieved the healing with satisfactory appearance.Conclusions After facial tumour resection, the large coloboma raw surface can be repaired by using the skin graft, skin flaps after tumor resection or free skin flap if designed reasonably.The procedure of operation is simple and the therapeutic effect is satisfactory.

Objective To understand the current status of knowledge, attitude and behaviors on reproductive health among the teen-agers in Shanghai. Methods During May to September 2013, the survey was conducted among 4 942 students in eight high schools, eight vocational high schools, eight middle schools and two universities in four districts in Shanghai, using stratified cluster sampling method. Results The subjects included 2 456 males and 2 486 females with an average age of (16.84 ±1.53). The teen-agers had a low level of knowledge on reproductive health, especially the knowledge of pregnancy and contraception, and there was significant difference in gender and age groups respectively.The attitude towards sex-related behaviors was open.The acceptance rate of premarital sexual behavior, unmarried cohabitation, premarital pregnancy, one-night stand and multiple sexual partners was 66.9%, 62.7%, 34.0%, 28.1%, and 28.1% respectively.According to multivariate logistic regression analysis, the acceptance of premarital sexual behavior was correlated to gender, education level, knowledge of condom and sexually transmitted diseases, and love behavior ( P <0.05 ) . Conclusion The teen-agers in Shanghai have poor knowledge of reproductive health and an open attitude towards sex-related behaviors.It is important to pay attention to the education and guidance of teen-agers'reproductive health knowledge, so as to help them build a complete and comprehensive system on reproductive health knowledge and skills.

Objective To understand the developmental effects induced by CdSe /ZnS quantum dots(QDs)on zebrafish embryos.Methods Zebrafish embryos were exposed to 0,0.5,1,2,4,8 and 16 nmol/L of CdSe /ZnS QDs,and the typical toxicological indexes were recorded at five time points respectively (24 hours post fertilization (hpf),48 hpf, 72 hpf,96 hpf,120 hpf).Results The results showed that the median lethal concentration (LC50 )for zebrafish embryos after 120 hpf was 21.38 nmol/L(95% CI =17.21 -26.57).The frequency of spontaneous movement in 60 seconds after 24 hpf,the frequency of heart beat in 60 seconds after 48 hpf,the hatching rate and the mortality rate were obviously affected by CdSe /ZnS QDs.Several abnormalities and toxic symptoms caused by CdSe /ZnS QDs at 8 nmol/L and 16 nmol/L were observed including pericardial edema,liver atrophy,non -depleted yolk,intestinal abnormal development and muscle degeneration after 120 hpf.Conclusion High level of CdSe /ZnS QDs (more than 8 nmol/L)could induce toxic effects on zebrafish embryonic development.