Adenosine triphosphate(ATP),as the core energy metabolism molecule in living systems,has dynamic changes closely related to fundamental physiological processes.To meet the urgent demand for spatiotemporal ATP detection in vivo and in situ,the development of highly sensitive multifunctional synchronous sensing fluorescent probes has become a recent research focus.These dual-function probes achieve fluorescence detection of dual targets by designing recognition sites for ATP alongside biological factors or microenvironment parameters such as reactive oxygen/nitrogen/sulfur species,metal ions,and enzymes,enabling physiological/pathological state correlation analysis through bioimaging.This paper systematically reviews recent advances in fluorescent probes for the collaborative detection of ATP and key biomolecules.It specifically examines probe construction strategies based on specific molecular recognition mechanisms(e.g.,metal coordination competition,electrostatic interactions,and host-guest recognition),multi-modal optical signal transduction mechanisms(ratiometric fluorescence,fluorescence lifetime,and photodynamic therapy),and their applications in pathological models such as oxidative stress monitoring,metal homeostasis imbalance,and enzyme activity co-detection.Finally,from the perspective of molecular probe engineering,current challenges and future research directions are proposed to provide methodological support for precise analysis of ATP-related life process regulation networks.

Objective To understand the implementation status of"Diagnosis of Ascariasis"(WS/T 565-2017)and provide a scientific basis for promoting,revising,and improving the Standard.Methods Using the convenient sampling method,the investigation targeted professional and technical personnel at the provincial,city,county,and township levels engaged in parasitic disease prevention,control,or diagnosis and treatment in Anhui and Sichuan provinces.No less than 150 individuals were included in each province.The implementation survey of Diagnosis of Ascariasis(WS/T 565-2017)was conducted by the subjects completing a questionnaire by themselves.Results The response rate to the questionnaire was 91.90%(386/420).The awareness and utilization rates of the Standard were 81.87%and 49.22%,respectively and both increased with age(χ2 trend=7.977 and 19.016,respectively,P＜0.01).Respondents with college degrees(90.72%)had a higher awareness rate(χ2=8.619,P＜0.05).In terms of utilization rate,males(58.38%),those with college degrees(67.01%),staff members of provincial-level units(77.78%),and personnel in medical institutions(71.43%)had higher utilization rates(χ2=13.486,17.166,8.426,and 5.956,respectively,all P＜0.05).The survey indicated that 57.77%of the work units of respondents have conducted promotional activities,and 53.89%of the work units of respondents have sent personnel to participate in training.Moreover,this proportion tended to increase as the unit level decreased(χ2 trend=9.403 and 14.729,P＜0.01).The level of participation in publicity and training by medical institutions(89.29%)was significantly higher than that of disease control institutions(55.31%and 51.12%,respectively,χ2=12.290 and 15.225,P＜0.01).Furthermore,training participation is a crucial factor in enhancing awareness rates.A total of 368 respondents(95.34%)reported that their work units have conducted testing for ascariasis.Additionally,378 individuals(97.92%)believe that the Standard is"applicable"or"basically applicable,"while 369(95.60%)felt that no revisions were needed.Conclusions The results indicated that"Diagnosis of Ascariasis"(WS/T 565-2017)remains applicable to the diagnostic needs of ascariasis and it is recommended to strengthen its promotion and implementation.

To explore the value of portable oto-endoscopy system in clinical teaching of otolaryngology residents.

Objective The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide (LPS) induced septic cardiac dysfunction.Methods Specific pathogen-free chicken embryos (n = 120) were allocated untreated control, phosphate buffer solution (PBS) vehicle, PBS with ethanol vehicle, LPS (500 ng/egg), LPS with quercetin treatment (10, 20, or 40 nmol/egg, respectively), Quercetin groups (10, 20, or 40 nmol/egg). Fifteen-day-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity. At embryonic day 19, the hearts of the embryos were collected for histopathological examination, RNA extraction, real-time polymerase chain reaction, immunohistochemical investigations, and Western blotting.Results They demonstrated that the heart presented inflammatory responses after LPS induction. The LPS-induced higher mRNA expressions of inflammation-related factors (TLR4, TNFα, MYD88, NF-κB1, IFNγ, IL-1β, IL-8, IL-6, IL-10, p38, MMP3, and MMP9) were blocked by quercetin with three dosages. Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of TLR4, IFNγ, MMP3, and MMP9 when compared with the LPS group. Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1, and significantly decreased protein expression of claudin 1 when compared with the LPS group. Quercetin significantly downregulated autophagy-related gene expressions (PPARα, SGLT1, APOA4, AMPKα1, AMPKα2, ATG5, ATG7, Beclin-1, and LC3B) and programmed cell death (Fas, Bcl-2, CASP1, CASP12, CASP3, and RIPK1) after LPS induction. Quercetin significantly decreased immunopositivity to APOA4, AMPKα2, and LC3-II/LC3-I in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of AMPKα1, LC3-I, and LC3-II. Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group.Conclusion Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy, programmed cell death, and myocardiocytes permeability.

To explore the value of portable oto-endoscopy system in clinical teaching of otolaryngology residents.

Background::Cerebrovascular disease (CVD) ranks among the foremost factors responsible for mortality on a global scale. The mortality patterns of CVDs and temporal trends in China need to be well-illustrated and updated.Methods::We collected mortality data on patients with CVD from Chinese Center for Disease Control and Prevention’s Disease Surveillance Points (CDC-DSP) system. The mortality of CVD in 2020 was described by age, sex, residence, and region. The temporal trend from 2013 to 2019 was evaluated using joinpoint regression, and estimated rates of decline were extrapolated until 2030 using time series models.Results::In 2019, the age-standardized mortality in China (ASMRC) per 100,000 individuals was 113.2. The ASMRC for males (137.7/10 5) and rural areas (123.0/10 5) were both higher when stratified by gender and urban/rural residence. The central region had the highest mortality (126.5/10 5), the western region had a slightly lower mortality (123.5/10 5), and the eastern region had the lowest mortality (97.3/10 5). The age-specific mortality showed an accelerated upward trend from aged 55-59 years, with maximum mortality observed in individuals over 85 years of age. The age-standardized mortality of CVD decreased by 2.43% (95% confidence interval, 1.02-3.81%) annually from 2013 to 2019. Notably, the age-specific mortality of CVD increased from 2013 to 2019 for the age group of over 85 years. In 2020, both the absolute number of CVD cases and the crude mortality of CVD have increased compared to their values in 2019. The estimated total deaths due to CVD were estimated to reach 2.3 million in 2025 and 2.4 million in 2030. Conclusion::The heightened focus on the burden of CVD among males, rural areas, the central and western of China, and individuals aged 75 years and above has emerged as a pivotal determinant in further decreasing mortalities, consequently presenting novel challenges to strategies for disease prevention and control.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective:To explore chromosomal copy number variations (CNVs) and pregnancy outcomes in fetuses with mild to moderate isolated ventriculomegaly (IVM), but without other indications for invasive prenatal diagnosis.Methods:A retrospective analysis was conducted on clinical data of 215 singleton pregnancies with mild to moderate IVM (lateral ventricular width≥10-<15 mm) who underwent chromosomal microarray analysis (CMA), not indicated by advanced age, high risk in serum screening or abnormal history of pregnancy, at the Fujian Maternity and Child Health Hospital between June 2016 and March 2023. The 215 fetuses were grouped into mild ( n=167) and moderate ( n=48) IVM;unilateral ( n=142) and bilateral ( n=73) IVM; first diagnosis of IVM before 28 weeks ( n=138) and thereafter ( n=77). Anomalies other than IVM were excluded via three-dimensional color Doppler ultrasound examination between 22 and 26 weeks of gestation. Out of these cases, 129 were confirmed by fetal cranial MRI, 191 underwent chromosomal karyotype analysis, and 202 cases received cytomegalovirus DNA quantification test for amniotic fluid. The detection rates of pathogenic CNVs in various groups were compared using Fisher's exact test. Results:Among the 215 fetuses, 11 cases (5.1%) of chromosomal abnormalities were detected through CMA, including one trisomy 21, five pathogenic CNVs, and five CNVs of uncertain clinical significance. Within the pathogenic CNVs, there were two de novo mutations with 16p11.2 microdeletion and one de novo mutation with 16p11.2 microduplication, while one 16p11.2 microduplication and one Xp22.31 microdeletion were inherited maternally. Of the CNVs of uncertain significance, there were two 16p13.11 microduplications, each inherited from a different parent, one paternally and one maternally; meanwhile, family validation was refused in the other three cases with 3p22.1 microdeletion, 3p26.3 microdeletion, and 9q21.33q22.31 microduplication. The detection rate of pathogenic CNVs in the moderate IVM group was higher than that in the mild IVM group [6.3% (3/48) vs. 1.2% (2/167)], but the difference was not statistically significant ( P=0.083). Similarly, no significant difference was found in the detection rate of pathogenic CNVs when comparing the unilateral IVM group [2.1% (3/142)] with the bilateral IVM group [2.7% (2/73)], nor between the group diagnosed with VM before 28 weeks gestation [2.2% (3/138)] and that diagnosed ≥28 weeks [2.6% (2/77)] (both P>0.05). After the exclusion of fetuses with chromosomal pathogenic abnormalities ( n=11), cytomegalovirus infection( n=1), and additional ultrasound anomalies ( n=7), and several cases with missing data intrauterine outcomes were followed up in 169 IVM fetuses, including 104 (61.5%) improved, 60 (35.5%) unchanged, and five (3.0%) progressed. Follow-ups were successful for 194 women, of which eight pregnancies were terminated (including one trisomy 21, four pathogenic CNVs, one fetal cytomegalovirus infection, and two progressed to severe IVM). Among the 186 newborns, one was diagnosed with X-linked ichthyosis, and one child who progressed to severe IVM before born was followed until 20 months of age without notable phenotypic abnormalities. The rest 184 babies, including those with CNVs of uncertain clinical significance, exhibited no developmental abnormalities during follow-up between the ages of three months and six years. Conclusions:For those fetuses with isolated mild to moderate IVM, but without indications for prenatal diagnosis such as advanced maternal age, high risk in serum screening or abnormal history of pregnancy, remain having the risk for chromosomal aberrations, and 16p11.2 microdeletion/microduplication might be a frequent CNV associated with this condition. Aside from those with pathogenic chromosomal aberrations, fetal cytomegalovirus infection, or progressive enlargement of the lateral ventricles, most fetuses with isolated mild to moderate IVM have a good prognosis.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

objectiveTo explore the specific molecular mechanism of neuronal apoptosis induced by ATM inactivation. MethodsCGNs matured 7 days in vitro were cultured 8 h with 25 K， 5 K or 25 K medium containing ATM-specific inhibitors （Ku55933， 10 µmol/L； Ku60019， 15 µmol/L） for Hoechst stain and apoptosis analysis， or cultured for different lengths of time （2， 4， 8 h） to detect the protein expression levels of ATM， caspase-3 and cleaved caspase-3 by Western blotting. ATM and GADD45α specific siRNA was transfected into C6 cells and CGNs， and its interference efficiency was verified by q-PCR and Western blotting. CGNs matured for 5 days in vitro were transfected with ATM specific siRNA and pCMV-EGFP by calcium phosphate for 48 h， Hoechst staining and apoptosis analysis were performed. CGNs matured for 7 days in vitro were treated with 25 K medium containing ATM specific inhibitors for 8 h， transcriptome sequencing， differential expression gene identification and pathway enrichment analysis were performed. CGNs matured for 5 days in vitro were co-transfected with GADD45α specific siRNA and pCMV-EGFP by calcium phosphate for 48 h， then treated with 5 K or 25 K medium containing 15 µmol/L Ku6 for 8 h. Hoechst staining and apoptosis analysis were performed. ResultsCompared with the 25 K， CGNs nuclear pyknosis rate， cleaved Caspase-3 and ATM protein expression level were increased in the 5 K and ATM-specific inhibitor groups. The mRNA and protein expression levels of ATM and GADD45α were effectively reduced after transfection of ATM and GADD45α specific siRNA in C6 cells and CGNs. Compared with control， CGNs transfected with ATM specific siRNA showed a higher nuclear pyknosis rate. Totally 835 genes were identified to be up-regulated and 848 genes to be down-regulated in the Ku55933 treatment group； 454 genes were identified to be up-regulated and 314 genes to be down-regulated in the Ku6 treatment group； 274 genes were co-up regulated in the Ku5 and Ku60019 treatment groups， while 179 genes were co-down-regulated in the Ku5 and Ku6 treatment groups and the expression of ATM downstream target GADD45α was upregulated. The enrichment results showed that TNF signaling pathway， NF-κB signaling pathway and Apoptosis signaling pathway were significantly enriched. Compared with control， mRNA and protein expression levels of GADD45α were increased in inhibitor treatment and 5 K， while knocking down GADD45α resulted in a decrease in nuclear pyknosis rate in the Ku60019 and 5 K treatment group. ConclusionLoss of ATM activity induces GADD45α-dependent cerebellar granular neuronal apoptosis.