Objective To establish a sandwich enzyme-linked immunosorbent assay (ELISA) method for the quantitative detection of Chromogranin A (CHGA) in saliva, and to explore its preliminary application in the testing of saliva samples. Methods Recombinant human CHGA protein was used to immunize BALB/c mice, and monoclonal antibodies (mAbs) were prepared and screened using conventional hybridoma technology. A double-antibody sandwich ELISA detection method was constructed, and the matrix effect of saliva samples was optimized. This method was then applied to detect the concentration of CHGA in the saliva of stressed individuals. Results Twenty-one stable hybridoma cell lines secreting high affinity anti-human CHGA antibodies were obtained. A pair of detection antibodies with the best effect was selected, and the optimal coating concentration was determined to be 10 μg/mL, with the optimal dilution of detection antibodies being 1:32 000. The accuracy and reproducibility of this method were verified, with both intra-batch and inter-batch variation coefficients less than 15×, and the recovery rate between 80× and 120×. The matrix effect was further optimized to make it suitable for saliva sample detection. Saliva samples from individuals in different stress states were collected, and the CHGA levels were detected using the method established in this study, indicating its potential to reflect the intensity of stress. Conclusion A reliable saliva CHGA ELISA detection method has been successfully established, and its potential as a biomarker in stress-related research has been preliminarily explored.
Saliva/metabolism* ; Enzyme-Linked Immunosorbent Assay/methods* ; Humans ; Animals ; Mice, Inbred BALB C ; Mice ; Chromogranin A/immunology* ; Antibodies, Monoclonal/immunology* ; Female ; Male ; Reproducibility of Results ; Adult

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Early start denver model(ESDM)is a comprehensive early intervention approach for the children with autism spectrum disorder(ASD)between 12-month-old-36-month-old.The model is built upon the theoretical foundations of applied behavior analysis,denver model(DM),and pivotal response treatment,and it is one of the naturalistic developmental behavioral interventions.Compared with the other early intervention methods,ESDM is not limited by the environment of intervention;it encompasses all the areas of development during teaching practice and has been widely adopted for the early intervention of the children with ASD,and achieves the satisfactory therapeutic effect.The ESDM typically uses an intensive one-on-one intervention approach,but variabilities have emerged in its practical application,such as group ESDM(G-ESDM),parent-implemented ESDM(P-ESDM),and peer-mediated ESDM.In particular,G-ESDM and P-ESDM have provided the learning opportunities for more families,showing a broad application prospect.This study reviews the theoretical foundations,teaching models,and the effects of various intervention modalities of the ESDM in the treatment of ASD;combined with the domestic and international research findings,this study offers a reference for further studies on the mechanism of ESDM intervention for ASD.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To investigate the changing distribution and antibiotic resistance profiles of clinical isolates of Staphylococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Staphylococcus according to the unified protocol of CHINET(China Antimicrobial Surveillance Network)using disk diffusion method and commercial automated systems.The CHINET antimicrobial resistance surveillance data from 2015 to 2021 were interpreted according to the 2021 CLSI breakpoints and analyzed using WHONET 5.6.Results During the period from 2015 to 2021,a total of 204,771 nonduplicate strains of Staphylococcus were isolated,including 136,731(66.8％)strains of Staphylococcus aureus and 68,040(33.2％)strains of coagulase-negative Staphylococcus(CNS).The proportions of S.aureus isolates and CNS isolates did not show significant change.S.aureus strains were mainly isolated from respiratory specimens(38.9±5.1)％,wound,pus and secretions(33.6±4.2)％,and blood(11.9±1.5)％.The CNS strains were predominantly isolated from blood(73.6±4.2)％,cerebrospinal fluid(12.1±2.5)％,and pleural effusion and ascites(8.4±2.1)％.S.aureus strains were mainly isolated from the patients in ICU(17.0±7.3)％,outpatient and emergency(11.6±1.7)％,and department of surgery(11.2±0.9)％,whereas CNS strains were primarily isolated from the patients in ICU(32.2±9.7)％,outpatient and emergency(12.8±4.7)％,and department of internal medicine(11.2±1.9)％.The prevalence of methicillin-resistant strains was 32.9％in S.aureus(MRSA)and 74.1％in CNS(MRCNS).Over the 7-year period,the prevalence of MRSA decreased from 42.1％to 29.2％,and the prevalence of MRCNS decreased from 82.1％to 68.2％.MRSA showed higher resistance rates to all the antimicrobial agents tested except trimethoprim-sulfamethoxazole than methicillin-susceptible S.aureus(MSSA).Over the 7-year period,MRSA strains showed decreasing resistance rates to gentamicin,rifampicin,and levofloxacin,MRCNS showed decreasing resistance rates to gentamicin,erythromycin,rifampicin,and trimethoprim-sulfamethoxazole,but increasing resistance rate to levofloxacin.No vancomycin-resistant strains were detected.The prevalence of linezolid-resistant MRCNS increased from 0.2％to 2.3％over the 7-year period.Conclusions Staphylococcus remains the major pathogen among gram-positive bacteria.MRSA and MRCNS were still the principal antibiotic-resistant gram-positive bacteria.No S.aureus isolates were found resistant to vancomycin or linezolid,but linezolid-resistant strains have been detected in MRCNS isolates,which is an issue of concern.

Objective:To systematically assess the risk factors for acute pancreatitis in pregnancy (APIP) in China in recent 10 years.Methods:Acute pancreatitis, pregnancy, risk factors and clinical features were used as search terms. Case-control studies on APIP in China were retrieved by computer from PubMed, Cochrane Library, Embase, CNKI, Wanfang, VIP and Chinese Biomedical Literature Database from December 2011 to December 2021. RevMan 5.4 software was utilized for Meta analysis.Results:A total of 1525 APIP patients (645 severe cases and 880 mild cases) were included in 26 literatures. Meta analysis showed that early pregnancy, late pregnancy, hyperlipidemia and biliary etiology were the risk factors for APIP. In the early pregnancy, 4.22% of patients were in the severe group and 10.43% were in the mild group; In the late pregnancy, 81.95% of the patients were in the severe group and 69.72% were in the mild group. The causes of hyperlipidemia accounted for 52.16% in the severe group and 22.69% in the mild group. The causes of biliary disease accounted for 27.96% in the severe group and 41.71% in the mild group. All the differences of the above indicators between groups were statistically significant (all P value <0.05). The age at onset, body mass index, serum C-reactive protein and triacylglycerol levels of severe patients were higher than those of mild patients, and were positively correlated with the severity of APIP ( MD values were 0.99, 65.97, 1.33, 6.44, 95% CI values were 0.03-1.96, 0.59-2.08, 23.43-108.50, 4.49-8.39, P values were 0.04, 0.0005, 0.002, <0.001). The levels of blood calcium and serum albumin were lower than those of mild patients, and were negatively correlated with the severity of APIP ( MD values were -0.37, -5.93, 95% CI values were -0.50--0.24, -9.11--2.75, P values were <0.001, 0.003). Conclusions:Acute pancreatitis can occur in all stages of pregnancy. Early pregnancy is mainly mild, and severe cases are more common in late pregnancy. Hypertriglyceridemic pancreatitis progresses rapidly, and tends to become more severe in China.

Chronic myeloid leukemia (CML) is a slowly progressing hematopoietic cell disorder. Sphingosine kinase 1 (SPHK1) plays established roles in tumor initiation, progression, and chemotherapy resistance in a wide range of cancers, including leukemia.However, small-molecule inhibitors targeting SPHK1 in CML still need to be developed. This study revealed the role of SPHK1 in CML and investigated the potential anti-leukemic activity of hirsuteine (HST), an indole alkaloid obtained from the oriental plant Uncaria rhynchophylla, in CML cells. These results suggest that SPHK1 is highly expressed in CML cells and that overexpression of SPHK1 represents poor clinical outcomes in CML patients. HST exposure led to G2/M phase arrest, cellular apoptosis, and downregulation of Cyclin B1 and CDC2 and cleavage of Caspase 3 and PARP in CML cells. HST shifted sphingolipid rheostat from sphingosine 1-phosphate (S1P) towards the ceramide coupled with a marked inhibition of SPHK1. Mechanistically, HST significantly blocked SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways. In addition, HST can be docked with residues of SPHK1 and shifts the SPHK1 melting curve, indicating the potential protein-ligand interactions between SPHK1 and HST in both CML cells. SPHK1 overexpression impaired apoptosis and proliferation of CML cells induced by HST alone. These results suggest that HST, which may serve as a novel and specific SPHK1 inhibitor, exerts anti-leukemic activity by inhibiting the SPHK1/S1P/ S1PR1 and BCR-ABL/PI3K/Akt pathways in CML cells, thus conferring HST as a promising anti-leukemic drug for CML therapy in the future.

Objective To investigate the fertility history and demand for reproductive health services of new residents in Shanghai. Methods A questionnaire survey was conducted among 1 358 new residents in 36 survey sites in 7 districts of Shanghai from July to September 2020. The content includes fertility history， induced abortion history， demand for reproductive health-related services， awareness rate of the Shanghai Family Planning Association and service access rate， etc. Results Among the new residents themselves and their spouses/sexual partners， 31.3% （374/1 194） had been pregnant once and 33.6% （401/1 194） had been pregnant twice； 46.3% （533/1 194）had one child and 29.7% （355/1 194）had two children. The difference of number of births among new residents with different residence time， those who did or did not possess permanent residency or residence permits， and those from different sources （urban or rural） was statistically significant （ χ ²=158.664， 50.263， 16.011， 114.419， all P <0.001）. Among the new residents themselves and their spouses / sexual partners， the proportion of induced abortion of more than once was 36.1%. The difference of the number of abortions of new residents with or without permanent residency was statistically significant （ χ ²=19.389， P <0.001）. The awareness rate of new residents of the harm of induced abortion to health was 92.1% （1 100/1 194）； There were significant differences in the scientific knowledge of harm of induced abortion to health among new residents with different local residence time and those with or without a residence permit （ χ ²=36.590， 20.926， both P <0.001）. The awareness rate of the Family Planning Association was 82.6% （986/1 194）， and the service access rate was 51.3% （613/1 194）. Permanent residency and residence permits are the main factors that affect the service accessibility of the Shanghai Family Planning Association. 44.8% （535/1 194） of new residents hope to receive reproductive health services in their place of residence， and they are most concerned about knowledge on good prenatal and postnatal care. Conclusion We should further publicize the "three-child" fertility policy， advocate a friendly fertility culture， and provide new residents with people-centered and accurate reproductive health services adapted to their needs through multi-sectoral cooperation， so as to improve their reproductive health level.

Brain functional network changes over time along with the process of brain development, disease, and aging. However, most of the available measurements for evaluation of the difference (or similarity) between the individual brain functional networks are for charactering static networks, which do not work with the dynamic characteristics of the brain networks that typically involve a long-span and large-scale evolution over the time. The current study proposes an index for measuring the similarity of dynamic brain networks, named as dynamic network similarity (DNS). It measures the similarity by combining the "evolutional" and "structural" properties of the dynamic network. Four sets of simulated dynamic networks with different evolutional and structural properties (varying amplitude of changes, trend of changes, distribution of connectivity strength, range of connectivity strength) were generated to validate the performance of DNS. In addition, real world imaging datasets, acquired from 13 stroke patients who were treated by transcranial direct current stimulation (tDCS), were used to further validate the proposed method and compared with the traditional similarity measurements that were developed for static network similarity. The results showed that DNS was significantly correlated with the varying amplitude of changes, trend of changes, distribution of connectivity strength and range of connectivity strength of the dynamic networks. DNS was able to appropriately measure the significant similarity of the dynamics of network changes over the time for the patients before and after the tDCS treatments. However, the traditional methods failed, which showed significantly differences between the data before and after the tDCS treatments. The experiment results demonstrate that DNS may robustly measure the similarity of evolutional and structural properties of dynamic networks. The new method appears to be superior to the traditional methods in that the new one is capable of assessing the temporal similarity of dynamic functional imaging data.
Aging/physiology* ; Brain/physiology* ; Brain Mapping ; Humans ; Magnetic Resonance Imaging/methods* ; Nerve Net/physiology* ; Transcranial Direct Current Stimulation/methods*

Objective To analyze the effects of Hual qi huang granules on children with mycoplasma pneumoniae pneumonia.Methods A randomized,multicenter parallel controlled clinical trial was carried out.A total of 3 000 cases of hospitalized children with mycoplasma pneumoniae pneumonia were selected.All of them were given treatment for mycoplasma pneumoniae pneumonia with macrolide antibiotics and symptomatic treatment.They were randomly divided into 2 groups:research group and control group.The children of research group were give oral Huai qi huang granules for three months.According to the classification of pneumonia,these two groups were divided into:lobar pneumonia research group,lobar pneumonia control group,lobular pneumonia research group,lobular pneumonia control group.The hospitalization duration of fever,length of hospital stay,the absorption area of lung inflammation and pneumonia severity sores were observed.The frequency of upper respiratory infections,bronchitis,pneumonia were observed in 3 months after discharge.Results 2 378 cases were investigated.The hospitalization duration of fever,length of hospital stay of research group were significantly shorter than that of in control group (P ＜ 0.001).The children with lobar pneumonia,2 weeks after treatment,the absorption of consolidation of the lobar pneumonia research group is significantly better than lobar pneumonia control group (P ＜0.001).After two weeks treatment,the pneumonia scores of lobar pneumonia research group is lower than lobar pneumonia control group (P ＜ 0.05).Followup of 3 months after hospital discharge,frequency of upper respiratory infection and bronchitis of research group,were significantly lower than that of control.In addition,appetite increased significantly in research group than control (P ＜ 0.001).There are 21 cases with drug associated adverse reactions (mild diarrhea),including 12 cases of research group,9 cases of control group,and there was no statistical significance (P ＞0.05).Conclusion Standard treatment combined with oral Huai qi huang granules in the treatment of mycoplasma pneumoniae pneumonia,can significantly shorten hospitalization duration of fever,length of hospital stay and reduce the severity score of pneumonia.Three months oral Huai qi huang granules can significant reduce the frequency of respiratory infections and bronchitis,also can increase patients appetite,and be safe.