ObjectiveTo investigate the anti-Alzheimer's disease （AD） effect of Dipsacus asper（DA） in the Caenorhabditis elegans model， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor α （PPARα）/transcription factor EB （TFEB） pathway. MethodsFirst， transgenic AD C. elegans individuals were assigned into the blank control， model， positive control （WY14643， 20 µmol·L^-1）， and low-， medium-， and high-dose （100， 200， and 400 mg·L^-1， respectively） DA groups. The amyloid β-42 （Aβ₄₂） formation in the muscle cells， the paralysis time， and the deposition of amyloid β-protein （Aβ） in the head were detected. The lysosomal autophagy in the BV2 cell model was examined by Rluc-LC3wt/G120A. The expression levels of lysosomal autophagy-related proteins LC3Ⅱ， LC3I， LAMP2， and TFEB were detected by Western blot. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of autophagy-related genes beclin1 and Atg5 and lysosome-related genes LAMP2 and CLN2 downstream of PPARα/TFEB. A reporter gene assay was used to detect the transcriptional activities of PPARα and TFEB. Immunofluorescence was used to detect the fluorescence intensity of PPARα， and the active components of the ethanol extract of DA were identified by UPLC-MS. RCSB PDB， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and Autodock were used to analyze the binding between the active components and PPARα-ligand-binding domain （LBD）. ResultsCompared with the model group， the positive control group and 200 and 400 mg·L^-1 DA groups showed prolonged paralysis time （P<0.05）， and all the treatment groups showed decreased Aβ deposition in the head （P<0.01）. DA within the concentration range of 50-500 mg·L^-1 did not affect the viability of BV2 cells. In addition， DA enhanced the autophagy flux （P<0.05）， up-regulated the mRNA levels of beclin1， Atg5， LAMP2， and CLN2 （P<0.05， P<0.01）， promoted the nuclear translocation of TFEB （P<0.05）， increased LAMP2 expression and autophagy flux （P<0.05， P<0.01）， and enhanced the transcriptional activities of PPARα and TFEB （P<0.01）. The positive control group and 200 and 400 mg·L^-1 DA groups showed enhanced fluorescence intensity of PPARα in the BV2 nucleus （P<0.01）. UPLC-MS detected nine known compounds of DA， from which 8 active components of DA were screened out. The docking results suggested that a variety of components in DA could bind to PPARα-LBD and form stable hydrogen bonds. ConclusionDA may reduce the pathological changes in AD by regulating the PPARα-TFEB pathway.

ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap-linear ion-trap mass spectrometry（UPLC-Orbitrap Fusion Lumos Tribrid-MS）， the plasma concentration of ziyuglycoside Ⅰ was determined at different time points after oral administration， and its pharmacokinetic characteristics in normal rats and rats with acute kidney injury were compared. MethodsRats were randomly divided into normal group and model group， the model group received intraperitoneal cisplatin（10 mg·kg^-1） to establish the acute kidney injury model， the normal group was given the same volume of saline. After successful modeling， rats in the normal and model groups were randomly divided into the normal low， medium and high dose groups（2.5， 5， 7.5 mg·kg^-1） and the model low， medium and high dose groups（2.5， 5， 7.5 mg·kg^-1）， 6 rats in each group， and the plasma was collected at different time points after receiving the corresponding dose of ziyuglycoside Ⅰ. Then， the concentration of ziyuglycoside Ⅰ in rat plasma was determined by UPLC-Orbitrap Fusion Lumos Tribrid-MS， and the drug-time curve was poltted. The pharmacokinetic parameters were calculated by Kinetica 5.1 software， and the differences in pharmacokinetic parameters between different administration groups were compared by independent sample t-test with SPSS 22.0. ResultsThe pharmacokinetic results showed that after receiving the different doses of ziyuglycoside Ⅰ， its concentration increased first and then decreased， and all of them reached the maximum plasma concentration at about 0.5 h. The area under the curve（AUC_0-t） and mean retention time（MRT_0-t） of normal and model rats increased with the increased dose， and the clearance（CL） decreased with the increasing dose. Compared with the normal group， the AUC_0-t was significantly increased（P<0.01）， peak concentration（C_max） and CL decreased in model rats at different doses， indicating that the physiological state of the rats could affect the absorption and elimination of ziyuglycoside Ⅰ in vivo. ConclusionThe pharmacokinetic characteristics of ziyuglycoside Ⅰ are quite different in normal rats and acute kidney injury model rats， which may be due to the change of the body environment in the pathological state， then lead to changes in absorption and metabolic processes.

Objective To analyze the operation of Measles Surveillance System (MSS) in Hebei Province, and to provide evidence for measles elimination. Methods Measles surveillance data was collected from the MSS from 2020 to 2023, and a modified weighted technology for order preference by similarity to an ideal solution (TOPSIS) method was used to evaluate the surveillance indexes of measles in Hebei Province. Results The operation quality of the measles surveillance system in Hebei Province was improved year by year, with the highest quality in 2023, and all the indicators reached the monitoring program standards. The quality of measles surveillance system was not balanced among cities, and the main influencing factor was the substandard sensitivity indicators. The quality of measles surveillance system was the highest in Baoding City and the lowest in Zhangjiakou City. Conclusion The measles surveillance system in Hebei province is running well, and the sensitivity of the surveillance system should be improved to keep the high-quality operation of the surveillance system.

[Objective] To investigate the factors associated with alanine aminotransferase (ALT) abnormalities in multi-ethnic blood donors across five Zang autonomous prefectures in the plateau regions of Qinghai Province, and to provide evidence for ensuring blood safety and formulating screening strategies. [Methods] A retrospective analysis was performed on the ALT abnormal test results of blood donors in the Zang autonomous prefectures of Qinghai from 2022 to 2024. The correlations between ALT levels and factors including gender, age, altitude, and infectious markers were investigated. [Results] The overall ALT unqualified rate among blood donors in this region was 9.01%. Significant differences in ALT levels were observed across genders and age groups (P<0.05). Variations in ALT abnormality rates were also noted among different plateau regions (P<0.05). Overall, ALT values exhibited an increasing trend with rising altitude. The average ALT unqualified rates were 11.19% in Zang donors, 7.96% in Han donors, and 4.79% in donors from other ethnic groups (P<0.05). No statistically significant association was observed between ALT abnormality and the presence of HBV/HCV infectious markers (P>0.05). [Conclusion] In the plateau areas of Qinghai, multi-ethnic blood donors have a relatively high ALT levels and ALT unqualified rates, showing distinct regional characteristics. ALT elevation in voluntary blood donors is related to non-pathological factors such as gender, age, and dietary habits, but not to infectious indicators.

Objective: To investigate the impact of RHAG 808A variant, commonly identified in the Chinese population, on RhAG protein, RhD and RhCE antigens expression through in vivo and in vitro expression analysis. Methods: A missense mutation of RHAG gene (c. 808G>A, p. Val270Ile) with high frequency was found in KMxD database. Bioinformatics analysis was performed using Polyphen-2 and Provean software. High resolution melting (HRM) method was utilized to screen for the variant carriers in the blood donors. The expression of RhAG protein, RhD and RhCE antigens on the surface of red cells of variant carriers were detected via flow cytometry. Wild-type and mutant vectors of RHAG were constructed and transfected into HEK 293T cells for in vitro expression analysis. Then, the expression of RhAG protein, RhD and RhCE antigens were analyzed by flow cytometry. Results: Polyphen-2 and Provean software suggested that the amino acid change (p. Val270Ile) of RhAG protein may be harmful or neutral respectively. Among the 999 blood donors from Guangzhou Blood Center, 4 homozygous carriers and 99 heterozygous carriers of RHAG 808A mutant allele were identified. The frequency of this allele was 5.4% (107/1 998). No significant differences in RhAG protein, RhD and RhCE antigens expression level was identified between the homozygous carriers, heterozygous carriers of RHAG 808A variant allele and the wild-type individuals. In vitro analysis for antigen expression study obtained the similar results. Conclusion: The RHAG 808A variant allele commonly identified in the Chinese population has no effect on the expression of RhAG protein, RhD and RhCE antigens, so the variant should be a population polymorphism site.

Objective To analyze the occurrence characteristics of adverse events following immunization (AEFI) of 23-valent pneumococcal polysaccharide vaccine (PPSV-23) in Hebei Province and to evaluate the safety of the vaccine. Methods AEFI cases related to vaccination of PPSV-23 in Hebei Province from January 1, 2020 to December 31, 2022 were collected through the AEFI surveillance module of Chinese Center for Disease Control and Prevention Information System. The incidence of reported AEFI cases were then analyzed and compared. Results The reported incidence rate of AEFI of PPSV-23 was 56.12 /100,000 doses, and the incidence rate of adverse reactions was 55.50 /100 000 doses. The incidence rate of common adverse reactions was 53.94/100 000 doses, and the incidence rate of rare adverse reactions was 1.56/100 000 doses. Most of the reported AEFI cases caused by PPSV-23 were common adverse reactions, which occurred mainly within one day after vaccination, and the overall regression was positive. Conclusion The 23-valent pneumococcal polysaccharide vaccine used in Hebei Province is safe，but its safety monitoring still needs to be strengthened.

Objective: To analyze the epidemiological and molecular characteristics of norovirus outbreaks in schools in Xicheng District of Beijing from 2017 to 2022, so as to provide evidence for the prevention and control of norovirus outbreaks in schools. Methods: Data of norovirus outbreaks in schools in Xicheng District, Beijing during 2017 to 2022 were collected and analyzed by descriptive epidemiological methods. Realtime PCR was used to detect the nucleic acid of group GⅠand GⅡnorovirus, the positive norovirus nucleic acid samples were sent to Beijing Center for Disease Control and Prevention for molecular typing. Results: From 2017 to 2022, 185 norovirus outbreaks were reported in schools in Xicheng District, including 166 cluster outbreaks and 19 outbreaks. A total of 2 044 cases were reported, with a total attack rate of 13.92%. There were two peaks in the outbreak time, which were from March to June after the spring semester and from October to December after autumn semester. Primary schools were the most common place of occurrence (101 cases), followed by nursery institutions (68 cases) and secondary schools (16 cases). There were statistically significant differences in the incidence rates among different sites(12.37%, 22.78%, 8.47%, χ2=263.34, P<0.01). There were significant differences in the incidence of vomiting, diarrhea, nausea and stomachache among different students (χ2=263.33, 90.58, 20.42, 30.29, P<0.01). Vomiting was the main symptom in primary school and nursery school children (96.41%, 98.28%), and the diarrhea rate was higher in middle school students (68.22%). The outbreaks were mainly caused by type GⅡ norovirus. The genotype from 2017 to 2021 showed the characteristics of diversity, mainly GⅡ.2[P16], but there was no significant advantage for the GⅡ.2 [P16] during 2019 to 2021. Conclusions The norovirus outbreak in schools in Xicheng district of Beijing from 2017 to 2022 are mainly caused by GⅡ type genome. The main genotype is GⅡ.2[P16]. Norovirus infection mainly occurred in primary schools and kindergartens. For the vulnerable populations, it is necessary to improve the capacity to early identification, student infectious disease management, active infection control and prevention measures, and pathogen surveillance and sporadic case monitoring.

Objective:To explore the etiology of primary amenorrhea,analyze its clinical features,and improve the level of clinical diagnosis and treatment.Methods:A retrospective analysis was conducted on the clinical data of 75 patients with primary amenorrhea who attended the gynecological endocrine clinic of Nanjing Women and Children's Healthcare Hospital from January 2020 to September 2022,and the etiology of their diagnosis was ana-lyzed.Results:aChromosomal karyotype analysis showed 14 cases(18.67％)of abnormal karyotypes,including 2 cases of autosomal abnormalities,7 cases of sex chromosome abnormalities,and 5 cases of sexual differentia-tion abnormalities.②According to reproductive hormones,there were 15 cases(20.00％)of hypogonadotropic a-menorrhea and 18 cases(24.00％)of hypergonadotropic amenorrhea.③By the location of the cause,utero-inferi-or genital tract amenorrhea was the most common in 23 cases(30.67％),including 20 cases of mayer-rokitan-sky-küster-hauser syndrome(MRKH syndrome)and 3 cases of androgen insensitivity syndrome(AIS).It was followed by ovarian amenorrhea in 18 cases(24.00％)including 6 cases of Turners syndrome,10 cases of 46,XX simple gonadal hypoplasia and 2 cases of 46,XY gonadal hypoplasia(Swyer syndrome);hypothalamic-pituitary amenorrhea in 17 cases(22.67％),including idiopathic hypogonadotropic hypogonadism(IHH)in 9 cases,Kall-mann s syndrome in 4 cases,and hyperprolactinemia in 4 cases;and also amenorrhea with hyperandrogenic mani-festations in 17 cases(22.67％),with a higher number of suspicious polycystic ovary syndrome in 16 cases.Con-clusions:Primary amenorrhea has a variety of etiologies and clinical features,and requires examination of sex hormones and pelvic ultrasound from the lower genital tract up to the central nervous system to find the site of the etiology and to optimize the diagnostic process;in the case of hypogonadotropic amenorrhea,chromosomal test is necessary.

Objective:To explore the etiology of primary amenorrhea,analyze its clinical features,and improve the level of clinical diagnosis and treatment.Methods:A retrospective analysis was conducted on the clinical data of 75 patients with primary amenorrhea who attended the gynecological endocrine clinic of Nanjing Women and Children's Healthcare Hospital from January 2020 to September 2022,and the etiology of their diagnosis was ana-lyzed.Results:aChromosomal karyotype analysis showed 14 cases(18.67％)of abnormal karyotypes,including 2 cases of autosomal abnormalities,7 cases of sex chromosome abnormalities,and 5 cases of sexual differentia-tion abnormalities.②According to reproductive hormones,there were 15 cases(20.00％)of hypogonadotropic a-menorrhea and 18 cases(24.00％)of hypergonadotropic amenorrhea.③By the location of the cause,utero-inferi-or genital tract amenorrhea was the most common in 23 cases(30.67％),including 20 cases of mayer-rokitan-sky-küster-hauser syndrome(MRKH syndrome)and 3 cases of androgen insensitivity syndrome(AIS).It was followed by ovarian amenorrhea in 18 cases(24.00％)including 6 cases of Turners syndrome,10 cases of 46,XX simple gonadal hypoplasia and 2 cases of 46,XY gonadal hypoplasia(Swyer syndrome);hypothalamic-pituitary amenorrhea in 17 cases(22.67％),including idiopathic hypogonadotropic hypogonadism(IHH)in 9 cases,Kall-mann s syndrome in 4 cases,and hyperprolactinemia in 4 cases;and also amenorrhea with hyperandrogenic mani-festations in 17 cases(22.67％),with a higher number of suspicious polycystic ovary syndrome in 16 cases.Con-clusions:Primary amenorrhea has a variety of etiologies and clinical features,and requires examination of sex hormones and pelvic ultrasound from the lower genital tract up to the central nervous system to find the site of the etiology and to optimize the diagnostic process;in the case of hypogonadotropic amenorrhea,chromosomal test is necessary.

Objective:To explore the etiology of primary amenorrhea,analyze its clinical features,and improve the level of clinical diagnosis and treatment.Methods:A retrospective analysis was conducted on the clinical data of 75 patients with primary amenorrhea who attended the gynecological endocrine clinic of Nanjing Women and Children's Healthcare Hospital from January 2020 to September 2022,and the etiology of their diagnosis was ana-lyzed.Results:aChromosomal karyotype analysis showed 14 cases(18.67％)of abnormal karyotypes,including 2 cases of autosomal abnormalities,7 cases of sex chromosome abnormalities,and 5 cases of sexual differentia-tion abnormalities.②According to reproductive hormones,there were 15 cases(20.00％)of hypogonadotropic a-menorrhea and 18 cases(24.00％)of hypergonadotropic amenorrhea.③By the location of the cause,utero-inferi-or genital tract amenorrhea was the most common in 23 cases(30.67％),including 20 cases of mayer-rokitan-sky-küster-hauser syndrome(MRKH syndrome)and 3 cases of androgen insensitivity syndrome(AIS).It was followed by ovarian amenorrhea in 18 cases(24.00％)including 6 cases of Turners syndrome,10 cases of 46,XX simple gonadal hypoplasia and 2 cases of 46,XY gonadal hypoplasia(Swyer syndrome);hypothalamic-pituitary amenorrhea in 17 cases(22.67％),including idiopathic hypogonadotropic hypogonadism(IHH)in 9 cases,Kall-mann s syndrome in 4 cases,and hyperprolactinemia in 4 cases;and also amenorrhea with hyperandrogenic mani-festations in 17 cases(22.67％),with a higher number of suspicious polycystic ovary syndrome in 16 cases.Con-clusions:Primary amenorrhea has a variety of etiologies and clinical features,and requires examination of sex hormones and pelvic ultrasound from the lower genital tract up to the central nervous system to find the site of the etiology and to optimize the diagnostic process;in the case of hypogonadotropic amenorrhea,chromosomal test is necessary.