ObjectiveTo investigate the possible mechanism of Jishe Qushi Capsule （脊蛇祛湿胶囊， JQC） in treating rheumatoid arthritis （RA） from the perspective of macrophage polarization mediated by neutrophil extracellular traps （NETs）. MethodsTwenty-four female SD rats were randomly divided into four groups， blank control group， model group， JQC group， and peptidylarginine deiminase 4 （PAD4） inhibitor group with 6 rats in each group. All groups but the blank control group were subjected to the induction of collagen-induced arthritis （CIA）. After successful model establishment， rats in the JQC group received intragastric administration of JQC 1.47 g/kg daily； rats in the PAD4 inhibitor group received intraperitoneal injections of the PAD4 inhibitor 4 mg/kg weekly. Rats in the blank， model， and PAD4 inhibitor groups received 2 ml of pure water daily by gavage. All treatments lasted 4 weeks. Joint lesions of each group were assessed on day 7， 14， 21， 28， and 35 after model establishment， and arthritis index （AI） scores were recorded. At 24 h after the final administration， histopathology of knee joints， including HE staining， safranin O-fast green staining， and TRAP staining， was performed. Flow cytometry was used to detect the counts of M1 and M2 macrophages in peripheral blood. ELISA was used to determine serum levels of TRACP， NETs， TNF-α， IL-1β， and iNOS. Western Blotting and qRT-PCR were used to measure MPO， NE， RANKL， OPG， and p65 protein and mRNA expression in knee cartilage tissue. ResultsCompared with the blank control group， the model group showed increased AI scores （P＜0.05）， marked synovial inflammatory infiltration， angiogenesis， and bone-cartilage destruction， increased TRAP-positive osteoclasts， increased M1 macrophages and decreased M2 macrophages， elevated serum TRACP， NETs， TNF-α， IL-1β， and iNOS （P＜0.05）， elevated MPO， NE， RANKL， and p65 protein/mRNA expression and decreased OPG protein/mRNA expression in knee cartilage tissue （P＜0.05）. Compared with the model group， the JQC group exhibited improved synovial inflammation， angiogenesis， and bone-cartilage damage， reduced AI scores on day 21， 28， and 35， decreased osteoclast counts， decreased M1 macrophages and increased M2 macrophages， reduced serum TRACP， NETs， TNF-α， IL-1β， and iNOS （P＜0.05）， decreased MPO， NE， RANKL， and p65 protein/mRNA expression and increased OPG expression （P＜0.05）. Compared with the PAD4 inhibitor group， the JQC group showed significantly lower AI scores， reduced M1 macrophages， increased M2 macrophages （P＜0.05）， reduced serum TRACP， TNF-α， IL-1β， and iNOS， decreased MPO， RANKL， and p65 expression， and increased OPG levels （P＜0.05）. ConclusionThe therapeutic mechanism of JQC for RA may involve inhibition of NETs formation， downregulation of the RANKL/NF-κB signaling pathway， and regulation of macrophage M1/M2 polarization imbalance， thereby suppressing osteoclastogenesis and inflammatory bone destruction.

Background: The impact of arterial blood pressure on cerebral oxygenation during immediate postnatal transition is poorly understood.Purpose: Here we investigated the association between arterial blood pressure (BP), cerebral tissue oxygenation index (cTOI), and cerebral fractional tissue oxygen extraction (cFTOE) during the immediate postnatal transition in preterm and full-term neonates. Methods: This prospective observational study included preterm and term neonates who did versus did not require respiratory support. Oscillometric BP was measured at 5, 10, and 15 minutes after birth. cTOI was continuously monitored using near-infrared spectroscopy, while arterial oxygen saturation (SpO2) was recorded using pulse oximetry. cFTOE was calculated from cTOI and SpO. cTOI and cFTOE values were correlated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) at all time points. Correlation and mixed-model analyses were then performed. Results: A total of 102 neonates were enrolled: 51 preterm (33 with, 18 without respiratory support) and 51 term (14 with, 37 without respiratory support). In preterm neonates requiring respiratory support, cTOI was positively correlated with DABP at all time points and with MABP at 15 minutes. cFTOE was negatively correlated with MABP and DABP throughout the experiment and with SABP at 5 minutes. No significant correlations were observedamong the other groups. A mixed-model analysis showed that MABP and DABP were significantly associated with cFTOE but not cTOI independent of gestational age or respiratory support. Conclusion Among preterm neonates requiring respiratory support, cTOI and cFTOE were associated with arterial BP during the immediate neonatal transition. Only cFTOE showed a slight association with BP among stable preterm and full-term neonates. These findings suggest impaired cerebral autoregulation in compromised preterm infants during the immediate postnatal transition.

Objective: This study employed next-generation sequencing (NGS) for large-scale genotyping of 42 blood group systems in blood donors to evaluate its applicability in multi-system blood group identification and rare blood type repository construction, while exploring the complementary value of third-generation sequencing (TGS) in haplotype phasing and variant capture in regions with insufficient sequencing depth for ABO ambiguous samples. Methods: A total of 562 regular blood donors (median donation frequency 11 times) from a blood center were enrolled. NGS was used for genotyping of 42 blood group systems, with a focused analysis on 12 systems essential for rare blood type repository construction: MNS, Lutheran, Kell, Duffy, Kidd, Diego, Yt, Colton, Gerbich, Ok, H, and I. TGS was employed to resolve haplotype phasing (i. e., determining whether different mutation sites are located on the same chromosome) in 12 ABO samples with discrepancies between forward and reverse typing. Serological and genotyping results were compared for MNS, Duffy, Kidd, Lewis, and ABO systems. Results: NGS-based genotyping revealed that Fy (a-b+) in the Duffy system accounted for 0.87% (4/458), and Di (a+b+) in the Diego system accounted for 10.62% (31/292). The Lutheran, Kell, Yt, Colton, H, Ok, I, and Gerbich systems exhibited near-uniform phenotype distributions. Among the 12 ABO ambiguous samples, NGS yielded multiple possible genotype combinations in 5 cases due to inability to phase alleles, whereas TGS uniquely resolved the genotypes through long-read sequencing. In one case, NGS detected only 2 mutation sites due to insufficient sequencing depth, while TGS identified all 11 sites and assigned the A1 phenotype. Concordance rates between serology and genotyping were: Duffy 96.55% (140/145), ABO 96.43% (513/532), Kidd 94.17% (97/103), MNS 85.07% (57/67), and Lewis 68.18% (75/110). In the MNS system, 7 of 8 samples serologically typed as M+N+ but genotyped as M-N+ carried GYPB variants. Lewis discrepancies predominantly featured genotype Le (a-b+) with serological phenotypes of Le (a+b-), Le (a+b+), or Le (a-b-). The NGS platform completed sequencing of 192 samples within 2 weeks. Conclusion: The tiered genotyping strategy combining NGS, TGS, and serology enables multi-system blood group identification in large-scale blood donor populations. TGS provides complementary value in phasing ambiguous ABO samples and detecting variants in regions with insufficient sequencing depth. This study provides a technical framework and baseline frequency data for the expansion of a local rare blood type repository. However, standardization and cost-effectiveness of this strategy require further validation with expanded sample sizes, and serological confirmation should be retained for secretion status-related systems such as Lewis.

Objective To investigate the epidemiological characteristics and risk factors of non-alcoholic fatty liver disease in Jincheng between 2015 and 2020. Methods Clinical data of 8,578 medical check-ups at Physical Examination Center of ou hospital from January 2015 to December 2020 were retrospectively selected. The prevalence of non-alcoholic fatty liver disease in the last 5 years was recorded, and Logistic regression was utilized to identify the risk factors for the development of non-alcoholic fatty liver disease. Results The overall prevalence of non-alcoholic fatty liver disease in Jincheng was 14.57% in 2015-2020. The prevalence of non-alcoholic fatty liver disease was higher in men than in women (16.99% vs 10.98%) and highest in the 40-59 age group (18.76%). No statistical difference was reported in blood urea nitrogen (BUN) and serum creatinine (Scr) between groups (P>0.05), while statistical difference was found in diabetes, hypertension, body mass index (BMI), waist circumference, weekly exercise frequency, daily vegetable intake, triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT) and uric acid (UA) between two groups (P<0.05). Multivariate Logistic regression analysis denoted that BMI (OR=2.794, 95% CI: 1.745-4.550), waist circumference (OR=2.586, 95% CI: 1.585-4.299), diabetes (OR=0.644, 95% CI: 1.425-2.781), hypertension (OR=1.479, 95% CI: 1.121-2.290), weekly exercise ≥6h (OR=0.617, 95% CI: 0.519-0.709), daily vegetable intake ≥300g (OR=0.590, 95% CI: 0.467-0.652), TG (OR=1.481, 95% CI: 1.122-1.996), TC (OR=1.562, 95% CI:1.143-2.135), LDL-C (OR=1.440, 95% CI: 1.139-2.048), HDL-C (OR=0.656 , 95% CI: 0.587-0.783) , ALT (OR=1.591, 95% CI: 1.056-2.183), and UA (OR=1.412, 95% CI: 1.009-1.887) were risk factors for non-alcoholic fatty liver disease (P<0.05) . Conclusion The prevalence of non-alcoholic fatty liver disease in Jincheng City from 2015 to 2020 is 14.57%, the prevalence of males is higher than that of females, and the prevalence rate is the highest in the 40-59 age group. Moreover , diabetes mellitus , hypertension , BMI , waist circumference , weekly exercise , daily vegetable intake , serum TG, TC, LDL-C, HDL-C, ALT, and UA are all associated with the risk of the disease.

Keratoconus(KC)is a blinding eye disease caused by a variety of factors, with its pathogenesis still not well understood. In recent years, it has been discovered that sex hormones and prolactin-induced protein(PIP)have a profound impact on the cornea, with more noticeable changes when there are abnormalities in their body content. It has been found that various sex hormone receptors are distributed in the cornea. Based on this, this article reviews a multitude of studies on how sex hormones and PIP affect the cornea, along with relevant clinical research. It has been observed that sex hormones and PIP also play a role in KC patients and influence the occurrence and progression of KC. Additionally, it has been noted that pregnant and lactating women may be more susceptible to KC. Sex hormones and PIP have the potential to become new diagnostic and therapeutic targets. This article not only provides new insights but also offers important references for clinical practice.

Keratoconus(KC)is a blinding eye disease caused by a variety of factors, with its pathogenesis still not well understood. In recent years, it has been discovered that sex hormones and prolactin-induced protein(PIP)have a profound impact on the cornea, with more noticeable changes when there are abnormalities in their body content. It has been found that various sex hormone receptors are distributed in the cornea. Based on this, this article reviews a multitude of studies on how sex hormones and PIP affect the cornea, along with relevant clinical research. It has been observed that sex hormones and PIP also play a role in KC patients and influence the occurrence and progression of KC. Additionally, it has been noted that pregnant and lactating women may be more susceptible to KC. Sex hormones and PIP have the potential to become new diagnostic and therapeutic targets. This article not only provides new insights but also offers important references for clinical practice.

AIM:To explore the therapeutic effects of Liuwei-Dihuang decoction(LD)on ovarian function in pre-mature ovarian failure(POF)mice,and to uncover the role of the Notch signaling pathway in its mechanism.METHODS:A mouse model of POF was constructed through intraperitoneal injection of cyclophosphamide/busulfan.Subsequently,the mice were randomly divided into six groups(n=12 per group):control,POF model,low-dose LD(LD-L),medium-dose LD(LD-M),high-dose LD(LD-H),and positive drug(0.7 mg/kg diethylstilbestrol)groups.The ovarian histopathologi-cal alterations were assessed by hematoxylin-eosin(HE)staining.Serum levels of follicle-stimulating hormone(FSH),anti-Müllerian hormone(AMH),and estradiol(E2)were quantified via ELISA assays.Immunohistochemistry(IHC)was conducted to compare the expression level of cell proliferation marker Ki-67 in mouse ovarian tissues among the groups.The expression of proteins involved in the Notch pathway components[Notch1,Notch2,Jagged1(JAG-1),and hairy and enhancer of split 1(Hes1)]was determined via IHC and Western blot,while the corresponding mRNA levels of Notch1,Notch2,JAG-1,JAG-2,Hes1,and Hes5 were quantified through the qPCR analysis.RESULTS:Ovarian weight was significantly higher,and the number of atretic follicles was significantly lower in the LD-H and positive drug groups com-pared to the model group(P<0.05).However,serum FSH levels were decreased(P<0.01),whereas those of E2 and AMH were elevated in both treatment groups compared with the model group(P<0.01).In the LD-H group,the expres-sion of key molecules of the Notch pathway components was increased at the protein and mRNA level compared with the model group(P<0.01).CONCLUSION:LD ameliorates ovarian dysfunction in POF mice via activating the Notch sig-naling pathway.

Objective:To explore the predictive value of serum Dickkopf-related protein 1 (DKK1) and chemokine 21 (CCL21) expression for the pulmonary fibrosis progression in patients with rheumatoid arthritis associated interstitial lung disease (RA-ILD).Methods:A prospective study method was used. One hundred and eight patients with RA-ILD (RA-ILD group) and 108 patients with simple rheumatoid arthritis (RA group) from September 2020 to July 2023 in Jincheng People's Hospital were selected. The patients with RA-ILD were treated with disease-modifying antirheumatic drugs and anti fibrotic drugs. Before treatment, the serum DKK1, CCL21, C-reactive protein (CRP), anti cyclic citrullinated peptide antibody (ACPA), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) salivary liquefied glycan antigen 6 (KL-6) were detected; the 28 joints disease activity score (DAS28) and Warrick score were assessed. The patients with RA-ILD were followed up for 1 year, and the occurrence of pulmonary fibrosis progression was recorded. The patients with pulmonary fibrosis progression were included in the progressive subgroup and vice versa in the stable subgroup. Multivariate Logistic regression was used to analyze the independent risk factors for predicting pulmonary fibrosis progression within 1 year in patients with RA-ILD. The predictive value of serum DKK1 and CCL21 for predicting the pulmonary fibrosis progression within 1 year in patients with RA-ILD was analyzed by receiver operating characteristic (ROC) curve. The decision curve of serum DKK1 and CCL21 to predict the pulmonary fibrosis progression within 1 year in patients with RA-ILD was plotted using the R language package.Results:The DKK1 in RA-ILD group was significantly lower than that in RA group: (76.02 ± 9.80) ng/L vs. (86.44 ± 9.26) ng/L, the CCL21 was significantly higher than that in RA group: (202.02 ± 25.86) ng/L vs. (172.42 ± 18.35) ng/L, and there were statistical differences ( P<0.01). The patients with RA-ILD were followed up for 1 year, 25 cases (23.15%) developed pulmonary fibrosis progression (progressive subgroup), and 83 cases did not develop pulmonary fibrosis progression (stable subgroup). The Warrick score, CCL21, ACPA and KL-6 in progressive subgroup were significantly higher than those in stable subgroup: (11.80 ± 3.56) scores vs. (7.75 ± 1.81) scores, (224.53 ± 27.26) ng/L vs. (195.25 ± 21.32) ng/L, (452.46 ± 38.35) kU/L vs. (414.37 ± 31.63) kU/L and (466.35 ± 42.32) kU/L vs. (416.82 ± 38.34) kU/L, the DKK1 was significantly lower than that in stable subgroup: (68.65 ± 8.24) ng/L vs. (78.24 ± 9.15) ng/L, and there were statistical differences ( P<0.01); there were no statistical differences in DAS28, RF, ERS and CRP between the two subgroups ( P>0.05). Multivariate Logistic regression analysis result showed that Warrick score, DKK1, CCL21, ACPA and KL-6 were independent risk factors for predicting pulmonary fibrosis progression within 1 year in patients with RA-ILD ( OR = 2.601, 0.752, 1.110, 1.062 and 1.038; 95% CI 1.227 to 5.517, 0.578 to 0.978, 1.019 to 1.209, 1.009 to 1.118 and 1.001 to 1.076; P<0.05). The ROC curve analysis result showed that the area under the curve of DKK1 and CCL21 for predicting pulmonary fibrosis progression within 1 year in patients with RA-ILD was 0.779 and 0.795, with optimal cutoff values of 74.750 and 207.615 ng/L. The area under the curve of DKK1 combined with CCL21 for predicting pulmonary fibrosis progression within 1 year in patients with RA-ILD was 0.873. The decision curve analysis result showed that the DKK1 combined with CCL21 for predicting pulmonary fibrosis progression within 1 year could improve the predictive value (the maximum benefit rate was 23.15%). Conclusions:Compared with RA patients, RA-ILD patients have decreased serum DKK1 levels and increased CCL21 levels. In patients with RA-ILD, the low expression of DKK1 and high expression of CCL21 are the risk factors of pulmonary fibrosis progression, and detecting serum levels of DKK1 and CCL21 can predict the risk of pulmonary fibrosis progression.

Objective:The clinical symptoms of children with global developmental delay (GDD) were analyzed to provide the scientific basis for the intervention of children with GDD.Methods:The results of the neuro-psychobehavioral scale were collected from 32 511 children with GDD from June 2020 to November 2023. Inclusion criteria: Children diagnosed with GDD according to the Diagnostic and Statistical Manual of Mental Disorders-V, ages 0.0 to 4.9 years. Exclusion criteria: children with common hearing impairment and visual impairment. The Chi-square tests were used for statistical analysis.Results:There were more boys than girls with GDD in outpatient clinics (68.2% vs. 31.8%). Among the children, the proportion of developmental delay in 5, 4, 3, and 2 domains was 31.1%, 23.4%, 22.9% and 22.6% respectively. The rate of delay in 2-3 domains was lower in boys (41.9%) than in girls (53.1%). The rate of delay in 4-5 domains was higher in boys (58.1%) than in girls (46.9%) ( χ2=352.11, P<0.001). Overall, outpatient GDD decreased with age. From 1.0-1.9 to 4.0-4.9 years of age, the proportion of children with developmental delay in 5 domains increased with age (18.2%, 36.4%, 43.9%, 52.4%). Among children aged 0.0-0.9 years, the proportion of 2 domains of developmental delay was higher (33.4%).Among children aged 1.0-1.9 years, the proportion of 2-3 domains of developmental delay was higher (30.7%). Among children aged 2.0-, 3.0-, 4.0-4.9 years, the proportion of developmental delay in 5 domains was higher (36.4%, 43.9%, 52.4%). In children with GDD, the fine motor delay occurred most frequently (85.1%), followed by social self-care (83.9%), language (79.0%), adaptation (62.3%), and gross motor (52.8%). The frequency of developmental delays in fine motor, adaptability, language, and social self-care in boys was higher than that in girls ( χ2=161.37, χ2=41.10, χ2=320.90, χ2=238.54, all P<0.001). The age groups with the highest delay incidence of gross motor, fine motor, adaptability, language, and social self-care were: 4.0-4.9 years (70.6%), 3.0-3.9 years (97.4%), 4.0-4.9 years (81.2%), 2.0-2.9 years (90.9%),2.0-2.9 years (95.4%). The proportions of fine motor delay in GDD children aged 0.0-0.9, 3.0-3.9 and 4.0-4.9 years were (74.5%, 97.4%, 96.8%) and the proportions of social self-care delay in GDD children aged 1.0- and 2.0-2.9 years were (92.1%, 95.4%). Peripheral and mild developmental delays were predominant in children with GDD. The proportion of severe language delay (6.4%) was higher than that in other fields. Conclusions:The proportion of GDD children with developmental delay in 4-5 domains was 54.5%. The most frequent domain of delay was fine motor. The frequencies of developmental delays in fine motor skills, adaptability, language, and social self-care in boys were higher than in girls. Most of the developmental delays in GDD children were marginal and mild. The rate of severe developmental delay in language was higher than in other domains.

Objective To construct a model for predicting ki-67 expression in hepatocellular carcinoma using the intratumoral and peritumoral radiomic features of contrast enhanced magnetic resonance imaging(CEMRI)in the arterial phase as well as clinical imaging features.Methods A total of 120 patients pathologically diagnosed with hepatocellular carcinoma(HCC)from January 2016 to December 2024 in No.910 Hospital of the Joint Logis-tics Support Force of the Chinese People's Liberation Army were retrospectively enrolled and randomly divided into a training set(84 cases)and a test set(36 cases)in a ratio of 7∶3.ITK-SNAP software was used to delineate the global region of interest(ROI)of HCC on the arterial phase MR images.The ROIs of all patients were automatically expanded outward by 2 mm,and then the intratumoral ROI areas were eliminated to obtain the peritumoral ROI.With the help of PyRadiomics software,1 198 intratumoral and peritumoral radiomic features were extracted.Spearman correlation analysis,maximum relevance-minimum redundancy(mRMR),and least absolute shrinkage and selection operator(LASSO)regression were used to reduce the data dimension and select the best features.Then,a radiomics model of the logistic regression(LR)machine learning algorithm was constructed.A combined model including clinical imaging features and radiomics features was established.The area under the curve(AUC),accuracy,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),calibration curve and decision curve analysis(DCA)were used to evaluate the efficacy of the intratumoral and peritumoral radiomics features combined with clinical imaging features model in predicting ki-67 expression in hepatocellular car-cinoma.Results The intratumor model exhibited an efficacy in predicting the expression of ki-67 in hepatocellular carcinoma with AUC values of 0.817 and 0.787 in the training set and test set,respectively.The peritumoral model showed an efficacy with AUC values of 0.805 and 0.633 in the training set and test set,respectively.The intratumoral and peritumoral model demonstrated AUC values of 0.874 and 0.836 in the training set and test set,respectively.The combined model constructed by integrating the intratumoral and peritumoral model with clinical imaging features yielded AUC values of 0.877 and 0.849 in the training set and test set,respectively,indicating clinical imaging features improved the performance of the model.DCA showed that the combined models all had good clinical benefits,with the intratumoral and peritumoral model performing the best.Conclusion The intratumoral and peritumoral radiomics model based on CEMRI arterial phase combined with clinical imaging data can accurately predict the expression of ki-67 in hepatocellular carcinoma.This combined model yields the best clinical benefit.