Aim To investigate the role of FRMD4A in autophagy of placental trophoblast cells in preeclampsia(PE).Methods The placental tissues and clinical data of normal pregnancy and PE were obtained,and the histopathological changes were observed by HE staining.An in vitro model of hypoxia-induced HTR-8/SVneo trophoblast cells was established.The expres-sions of LC3B Ⅱ/Ⅰ and p62 in placental tissues and hypoxic cell models were analyzed by Western blot.The expression of FRMD4A was detected by qRT-PCR,Western blot and immunofluorescence,and the correlation between the expression level of FRMD4A and the clinical characteristics of the subjects was ana-lyzed by Pearson correlation analysis.Hypoxia induced trophoblast cells were transfected with si-FRMD4A,and the expression of LC3 B Ⅱ/Ⅰ and p62 was analyzed by Western blot.Results Compared with the normal group,the expression of LC3B Ⅱ/Ⅰ in PE placental tissues and hypoxia-induced trophoblast models was significantly upregulated,while the expression of p62 was significantly downregulated.Meanwhile,the ex-pression of FRMD4A increased significantly.Moreo-ver,its expression was positively correlated with the maternal systolic blood pressure,diastolic blood pres-sure,and platelet count,but negatively correlated with the neonatal weight(P＜0.01).In addition,hypoxia-induced trophoblast cells transfected with si-FRMD4A showed a significant decrease in LC3B Ⅱ/Ⅰ and an increase in p62 expression.Conclusions The expres-sion of FRMD4A is upregulated in PE placenta and hy-poxia-induced trophoblast cell model.Interfering with it can significantly hinder the autophagy process of trophoblast cells,suggesting that it may serve as a po-tential molecular target to participate in the pathologi-cal process of PE.

Objective:To investigate the water improvement status and current disease situation in drinking water-borne endemic fluorosis areas of Taiyuan City, evaluate the effect of prevention and control measures, and provide a basis for optimizing control measures.Methods:Monitoring data from 2019 to 2024 for drinking water-borne endemic fluorosis in the diseased areas in Taiyuan City were collected from the Taiyuan Center for Disease Control and Prevention. A retrospective analysis was conducted on water improvement status, water fluoride content, dental fluorosis in children aged 8 - 12, skeletal fluorosis, and urinary fluoride monitoring results in all endemic villages.Results:From 2019 to 2024, all endemic villages in the six endemic counties (districts) of Taiyuan City completed water improvement. The number of water improvement projects each year was 75, 75, 72, 68, 64, and 57, respectively, with all projects operating normally. The qualified rates of water fluoride content each year were 81.33% (61/75), 100% (75/75), 98.61% (71/72), 75.00% (51/68), 87.50% (56/64), and 75.44% (43/57), respectively, with statistical significant differences ( χ2 = 36.99, P < 0.001). The detection rates of dental fluorosis each year were 18.19% (600/3 298), 14.42% (530/3 676), 11.14% (435/3 904), 11.13% (421/3 781), 11.59% (435/3 754), and 5.37% (299/5 567), respectively, with statistical significant differences ( χ2 = 386.42, P < 0.001). In 2024, 824 people were screened for skeletal fluorosis, with 250 cases showing positive symptoms and signs. Among the 250 positive cases, 210 underwent X-ray examination, detecting 170 skeletal fluorosis patients, with an X-ray positive rate of 80.95% (170/210) and a skeletal fluorosis detection rate of 20.63% (170/824). Urinary fluoride monitoring results showed that the geometric mean of urinary fluoride in villages with excessive water fluoride content was 2.95 mg/L, which was higher than the normal upper limit (1.60 mg/L). However, there was no statistically significant difference in urinary fluoride levels between skeletal fluorosis patients and non-skeletal fluorosis individuals ( Z = 0.78, P = 0.434). Conclusions:From 2019 to 2024, the drinking water-borne endemic fluorosis areas in Taiyuan City have undergone comprehensive water improvement and the water improvement projects are operating well. The qualified rate of water fluoride content has fluctuated, while the detection rate of dental fluorosis has decreased. Continuous monitoring is needed in the future to implement long-term water improvement measures and strengthen screening and treatment efforts for patients with fluorosis.

Objective To explore the clinical characteristics and improve the detection of early gastric cancer in patients with autoimmune gastritis(AIG).Methods A total 30 patients diagnosed with AIG who underwent endoscopic treatment for gastric early cancer at Beijing Friendship Hospital from 2018 to 2024 were enrolled retrospectively.The baseline characteristics,serological indicators,endoscopic and histopathological data of the patients were collected and analyzed.Further subgroup comparisons were conducted based on gender and Helicobacter pylori(Hp)infection status.Results Among the 30 patients,20 were female(66.7%),with a mean age of(64.93±7.68)years.Five patients(29.40%)were infected with Hp.The median values of pepsinogen Ⅰ(PG Ⅰ)and PG Ⅰ/Ⅱ ratio were 7.10 μg/L and 1.00,respectively,while the mean gastrin-17(G17)level was(121.10±120.15)pmol/L.The level of hemoglobin(Hb),free iron,ferritin,and vitamin B12 were all within the normal range.There were 21 cases(70.00%)with lesions located in corpus,among which 16 cases(53.33%)were type Ⅱa lesions and 15 cases(50.00%)were type Ⅰlesions.The predominant pathological type was tubular adenocarcinoma,with a total of 29 cases(96.67%).Female patients exhibited significantly lower levels of Hb(P=0.012)and free iron(P<0.001)compared to male patients.Female also had lower vitamin B12 level[(161.25±76.49)pg/mL,P=0.012],which was below the normal range and the difference was a statistically significant.No significant difference was observed between Hp-infected and non-infected patients.Conclusion Among AIG patients with early gastric cancer,female,corpus elevated or flat lesion and tubular adenocarcinoma were predominated.For female AIG patients with vitamin B12 deficiency,vigilance for the occurrence of gastric early cancer is warranted.

This paper uses literature and network data to systematically sort out the theoretical and practical foundations of global public health cooperation,combines expert interviews to conduct empirical analyses,and further explores China's strategies for participating in global public health cooperation through quantitative statistics and text mining of interview data,and proposes a plan for China's participation in global public health cooperation under the current international situation.Under the countercurrents to globalization,China should take its own public health capacity building as the foundation,put global security and health equity at the core,with a philosophy of open cooperation and sustainable development,actively promote bilateral and multilateral cooperation,focus on cultivating global health talents,and enhance the effectiveness of disease prevention and control by making use of existing platforms,international mechanisms and digital health technologies,so as to help build a Global Community of Health for All.

OBJECTIVE To investigate the protective effect and mechanism of saikosaponin C(SSC)on acute liver injury(ALI)in mice induced by carbon tetrachloride(CCl4)based on serum metabolomics.METHODS Forty mice were divided into blank group(water),model group(water),positive control drug group(Biphenyl diester drop pills,150 mg/kg),and SSC low-and high-dose groups(2.5,10 mg/kg)using the random number table method,with 8 mice in each group.They were given water/relevant drugs,once a day,for 7 consecutive days.One hour after the last administration,all mice were intraperitoneally injected with 0.2％CCl4 olive oil to induce ALI model,except for the blank group.After 17 hours of the modeling,the liver index of mice was calculated.The levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),lactate dehydrogenase(LDH),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and IL-1β in serum of mice were detected.The histopathological changes of liver tissue were observed.Meanwhile,the serum metabolomics of mice were analyzed by liquid chromatography-mass spectrometry.RESULTS Compared with the blank group,the levels of liver index,ALT,AST,LDH,TNF-α,IL-6,and IL-1β in the model group were significantly increased(P＜0.01).Hepatocytes were edema,vacuolar degeneration,more necrosis,and a large number of inflammatory cells were infiltrated.Compared with the model group,liver index and serum index levels of mice were significantly decreased(P＜0.05 or P＜0.01),accompanied by marked improvement in histopathological damage to the liver tissue.The metabolomics results showed that compared with the model group,there were 63 up-regulated and 256 down-regulated differential metabolites in the serum of mice in the SSC high-dose group,including prostaglandin B2,20-hydroxy-leukotriene B4,5-hydroxy-L-tryptophan,7α-hydroxycholesterol,etc.;these metabolites were primarily involved in metabolic pathways such as arachidonic acid metabolism,5-hydroxytryptamine synapse,primary bile acid biosynthesis.CONCLUSIONS SSC exerts a protective effect against CCl4-induced ALI by down-regulating the level of key metabolites such as prostaglandin B2 and 20-hydroxy-leukotriene B4,and then ruducing metabolic pathways such as arachidonic acid metabolism,5-hydroxytryptamine synapse,and primary bile acid biosynthesis.

Aim To explore the impact and mechanism of proprotein convertase subtilisin kexin 9(PCSK9)on the progression of abdominal aortic aneurysm(AAA).Methods 6～8 week old ApoE-/-mice were selected to estab-lish the AAA model.Angiotensin Ⅱ(Ang Ⅱ)was continuously infused through subcutaneous implantation of a micro-os-motic pump.The mice were fed with high-fat diet and killed after 28 days.The expression of PCSK9 in abdominal aor-tic smooth muscle cells was detected by immunohistochemistry and immunofluorescence in normal abdominal aortic blood vessels and AAA samples in human and mice.Primary cultured murine vascular smooth muscle cells(mVSMC)of C57BL/6 mice were treated with different concentrations of AngⅡ for 24 h,and the expression of PCSK9 mRNA and pro-tein was detected.PCSK9 overexpression and knockdown cell models were established,and mitochondrial reactive oxygen species(mtROS),mitochondrial membrane potential(MMP),mitochondrial permeability transition pore(MPTP)open-ing,and Z-DNA binding protein 1(ZBP1)protein expression were detected.Bioinformatics was used to analyze the dif-ferential expression of multiple single-cell sequencing datasets to obtain the key differentially expressed genes,and to study their expression and role in AAA.Results Immunohistochemistry and immunofluorescence results showed that PCSK9 expression in human and mouse AAA increased(P＜0.01),and co-localized with smooth muscle.Ang Ⅱ promoted PCSK9 expression in mVSMC in a concentration-dependent manner,the 2.0 μmol/L Ang Ⅱ group showed a 2.9-fold and 1.1-fold increase in the expression of PCSK9 mRNA and protein,respectively(P＜0.01),with the most significant effect observed.After successfully constructing PCSK9 overexpression and PCSK9 interference mVSMC models,PCSK9 overex-pression led to an increase in intracellular mtROS,a decrease in MMP,an increase in MPTP opening,and a decrease in cellular activity(P＜0.01);PCSK9 knockdown could reduce Ang Ⅱ induced increase in mtROS,decrease in MMP and MPTP opening;compared with the siNC+Ang Ⅱ group,the siPCSK9+Ang Ⅱ group showed a decrease in mtROS and an in-crease in the fluorescence brightness of MMP and MPTP(P＜0.05).Bioinformatics analysis revealed that ZBP1 was a core differentially expressed gene in AAA.Immunohistochemistry and immunofluorescence results showed that ZBP1 ex-pression in human and mouse AAA tissues increased,and co-localized with smooth muscle.Western blot results showed that PCSK9 overexpression or treatment with 2.0 μmol/L Ang Ⅱ could increase ZBP1 protein expression(P＜0.01),while PCSK9 knockdown could alleviate the increased ZBP1 expression caused by AngⅡ(P＜0.05).Conclusion PCSK9 may induce mitochondrial damage in smooth muscle cells,activate downstream molecule ZBP1 to cause cell damage,and promote the development of AAA.

Rheumatoid arthritis(RA)is a chronic autoimmune disease of unknown etiology that can cause joint destruction and deformity.As a small molecule cytokine,the chemokine C-X-C motif chemokine ligand 12(CXCL12)regulates the pathogenesis of rheumatoid arthritis by binding to the specific receptor CXC chemokine receptor 4(CXCR4).Therefore,based on the bio-logical characteristics of CXCL12 and CXCR4,this paper intro-duces the pathogenesis of CXCL12/CXCR4 in RA and summari-zes the progress in RA-related research,with the aim of providing clinical value for understanding the pathogenesis of RA and de-veloping novel therapeutic targets.

Objective:To improve the diagnosis and treatment of autoimmune hepatitis (AIH) in children by analyzing their clinical characteristics and outcomes.Methods:Case summary.The general data, clinical manifestations, laboratory parameters, liver pathology, treatment and outcomes of 6 AIH children diagnosed at Xi′an Children′s Hospital from January 2019 to March 2024 were retrospectively analyzed.Results:All the 6 patients were diagnosed with AIH-1, and 5 of them were female, accounting for 83.3%.The median age of onset was 6.2 years old.Three cases (50.0%) had insidious onset.Elevated hepatic aminotransferase levels were detected incidentally in 2 cases (33.3%).One case (16.7%) presented symptoms resembling those of viral hepatitis.Two cases (33.3%) were accompanied by extrahepatic autoimmune diseases.All the children tested positive for anti-nuclear antibodies with a titer ≥1∶80 or 1∶100.Four cases (66.7%), 3 cases (50.0%), and 1 case (16.7%) tested positive for anti-smooth muscle antibodies, anti-perinuclear neutrophil cytoplasm antibodies and anti-soluble liver antigen, respectively.Liver pathology showed infiltration of lymphocytes-plasma cells and moderate or severe interfacial inflammation in all the 6 cases.Two cases (33.3%) had rosettes.All the patients were given oral corticosteroids combined with Azathioprine or Mycophenolate mofetil.The patients were followed up for 24.8 (12.0-52.0) months, during which 3 cases (50.0%) had partial remission and 3 cases (50.0%) achieved complete remission.Four cases (66.7%) showed transaminase fluctuations during corticosteroid reduction or cessation.Conclusions:Autoantibodies and liver pathology are important evidence for diagnosing AIH in children.Immunosuppressants have a high remission rate in the treatment of this disease, but transaminase fluctuations are prone to occur during corticosteroid reduction or cessation.

Objective:To perform RHD gene detection on a blood sample with serological weak D phenotype.Methods:A specimen received by the People's Hospital of Zhijin County was serologically identified by the microcolumn gel method and saline method.RHD gene detection was conducted by the PCR-SSP method,and the full sequence determination of the 10 exons amplified was performed.The sequencing results were compared with the ISBT database to determine the genotype.Bioinformatics tool was used to predict the functional damage of mutant proteins,and Alphafold-3 was used for tertiary structural modeling of wild-type and mutant RhD proteins,and the structures of the two proteins were compared and analyzed to explore the reasons why mutations lead to weak serological manifestations.Results:The patient's genotype was identified as RHD*DV.5/RHD*01N.01 heterozygote,with the complete deletion of RHD genes on one chromosome,unable to express the D antigen.On the other chromosome,a G＞A mutation occurred at the 697th base of the 5th exon,resulting in a partial D phenotype.This mutation causes internal hydrogen bond changes at the 233 position of RhD protein,resulting in a change in the conformation of the protein,affecting binding to the corresponding antibody.Conclusion:The patient is a heterozygous mutant individual with RHD*DV.5/RHD*01N.01,exhibiting a partial D phenotype serologically.This variation is extremely rare and has been scarcely reported globally.

[Objective] To analyze the loss rate of platelet donors and evaluate the strategies for establishing a platelet donor bank. [Methods] A total of 1 443 donors who joined the HLA and HPA gene donor bank for platelets in Henan Province from 2018 to 2020 were included in this study. Data on the total number of apheresis platelet donations, annual donation frequency, age at enrollment, donation habits (including the number of platelets donated per session and whether they had previously donated whole blood), and enrollment location were collected from the platelet donor information management system. Donor loss was determined based on the date of their last donation. The loss rates of different groups under various conditions were compared to assess the enrollment strategies. [Results] By the time the platelet bank was officially operational in 2022, 421 donors had been lost, resulting in an loss rate of 29% (421/1 443). By the end of 2023, the overall cumulative loss rate reached 52% (746/1 443). The loss rate was lower than the overall level in groups meeting any of the following conditions: total apheresis platelet donations exceeding 50, annual donation frequency of 10 or more, age at enrollment of 40 years or older, donation of more than a single therapeutic dose per session, or a history of whole blood donation two or more times. Additionally, loss rates varied across different enrollment locations, with higher enrollment numbers generally associated with higher loss rates. [Conclusion] Through a comprehensive analysis of donor loss, our center has adjusted its strategies for establishing the donor pool. These findings also provide valuable insights for other blood collection and supply institutions in building platelet donor banks.