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 analyze the effects of biodegradable-polymer sirolimus-eluting stents (BP-SES) and durable polymer sirolimus-eluting stents (DP-SES) implantation on serum endothelin 1 levels and the incidence of coronary restenosis in patients with coronary heart disease (CHD).Methods:A total of 114 patients with CHD admitted to the First People's Hospital of Xianyang in Shaanxi Province from May 2022 to January 2024 were selected. According to the principle of comparable baseline characteristics between groups, patients were divided into two groups by random number table method, with 57 cases in each group. After pretreatment of diseased vessels, DP-SES group underwent implantation of DP-SES with appropriate length and diameter, while BP-SES group underwent implantation of BP-SES with appropriate length and diameter. After implantation, non-compliant balloons were used for in-stent post-dilation. Comparisons of vascular endothelial function, levels of inflammatory factors and hemodynamic indicators before operation and at 6 months between groups were made postoperatively, also, the incidence rates of major adverse cardiovascular events (MACE) and coronary restenosis within 6 months were also compared. Measurement data with normal distribution was expressed as “xˉ±s”, independent sample t-test was used on comparison between groups, paired t-test was used for intra-group comparisons before and after treatment. Counting data was expressed as rate or composition ratio, χ2 test was used on comparison between groups. Results:At 6 months after surgery, the levels of endothelin 1 and VEGF were lower in BP-SES group compared to DP-SES group,[(72±5) ng/L vs. (77±7) ng/L, (147±25) ng/L vs. (157±27) ng/L, t=3.76, P<0.001, t=2.16, P=0.033]. The level of nitric oxide was higher in BP-SES group compared to DP-SES group [(79±7) μmol/L vs. (76±8) μmol/L, t=2.46, P<0.001]. At 6 months after surgery, the levels of TNF-α, IL-1 and CRP in DP-SES group were higher than those before surgery, and were all higher compared to BP-SES group[(81±5) ng/L vs. (75±5) ng/L, (159±18) ng/L vs. (151±16) ng/L, (31±4) mg/L vs. (29±3) mg/L, t=6.87, P<0.001, t=2.24, P=0.027, t=2.51, P=0.014]. At 6 months after surgery, the level of whole blood viscosity and plasma viscosity in both group were lower than those before surgery, and the level of Hct in BP-SES group was lower than those before surgery, the differences were statistically significant ( P<0.001), while the differences between groups were not statistically significant( P>0.05). The difference of incidence rates of MACE and coronary restenosis within 6 months between groups before surgery and 6 months after surgery were not statistically significant [7.0%(4/57) vs. 12.3%(7/57), χ2=0.91, P=0.341; 3.7%(2/57) vs. 8.3%(5/57), χ2=0.61, P=0.443]. Conclusion:Both BP-SES implantation and DP-SES implantation could effectively restore coronary blood supply, and are highly safe. However, the former can reduce damage to vascular wall and better improve endothelial function in patients.

Objective:To analyze differences in the expression of routine laboratory parameters and cerebrospinal fluid (CSF) examination indicators between patients with non-neurosyphilis (syphilis without nervous system involvement) and those with neurosyphilis, to screen for key predictive factors, and to construct a predictive model for neurosyphilis.Methods:A retrospective analysis was conducted on the clinical data from patients with syphilis at the Fifth People's Hospital of Suzhou from 2019 to 2024. Patients with neurosyphilis and non-neurosyphilis who were hospitalized from November 2019 to June 2022 were included in the model cohort, and those hospitalized from January 2024 to October 2024 were included in the validation cohort. The patients' basic information and laboratory test indicators (including routine blood tests, CSF biochemical analysis, and syphilitic antibody tests) were collected. Statistical analysis was performed using the GraphPad software. The receiver operating characteristic (ROC) curve and the binary logistic regression method were used to analyze the predictive performance of key indicators in patients from the model cohort with SPSS software, and a predictive model for neurosyphilis was constructed. The performance of the neurosyphilis predictive model for neurosyphilis was validated based on relevant indicators from the validation cohort.Results:The model cohort included 99 patients with non-neurosyphilis (including 49 males and 50 females), and they were aged between 19 and 85 years, with an average age of 47 years; 69 patients with neurosyphilis were also included in the model cohort, including 58 males and 11 females, and they were aged between 26 and 73 years, with an average age of 51 years. The neurosyphilis group showed a significant increase in the median levels of CSF adenosine deaminase (1 U/L) and microprotein (711 mg/L), white blood cell counts (0.009 × 10?/L), as well as in the proportion of positive Pandy tests (35/69, 50.7%) compared with the non-neurosyphilis group (0 U/L, 309 mg/L, 0.002 × 10?/L, 2 /99 [2.0%], respectively, all P < 0.001). Based on the ROC curve analysis, the CSF microprotein and white blood cell count had relatively high discriminative ability (area under the ROC curve [AUC] > 0.85), while adenosine deaminase and the Pandy test showed moderate discriminative ability (0.7 < AUC < 0.85). According to the above four indicators, the logistic regression analysis showed that CSF microprotein combined with CSF white blood cell counts could construct the best predictive model for neurosyphilis, with a prediction accuracy rate of 0.980, a sensitivity of 98.5%, and a specificity of 89.9%. The prediction formula was logit (p) = -9.926 + 0.015 × microprotein + 362.33 × CSF white blood cell count, with a cutoff value of ≥ -0.867. The validation cohort enrolled 72 patients with non-neurosyphilis and 51 with neurosyphilis, and there were significant differences in CSF microprotein levels and white blood cell counts between the two groups (both P < 0.001). In the validation cohort, the predictive model demonstrated an accuracy of 86.2%, with a sensitivity of 83.6% and a specificity of 91.1% for predicting neurosyphilis. Conclusion:The predictive model for neurosyphilis constructed by combining CSF microprotein and CSF white blood cell count may contribute to the early differential diagnosis of neurosyphilis.

OBJECTIVE

This study aimed to estimate the incidence of hypertension and determine the risk factors for hypertension among apparently healthy adult Filipinos.

This observational prospective community-based study included apparently healthy adult individuals aged 20–50 years from the Life Course Study in Cardiovascular Disease Epidemiology (LIFECARE) Philippine cohort at baseline and followed-up after an average of four years. Sociodemographic data, psychosocial stress, and clinical and metabolic profiles were obtained and analyzed. Multivariable Cox regression analysis was performed to identify factors associated with the development of hypertension.

A total of 2,089 non-hypertensive participants were included, with 59% women and average age of 35 years (SD = 8.4). The incidence rate of hypertension was 38.1 per 1,000 person-years. The cumulative incidence of hypertension over a mean follow-up time of four years was 15.4% (95% CI = 13.9–17.0%). The risk of incident hypertension was higher among males (aHR=1.3, 95% CI: 1.0–1.8; p=0.044), ≥40 years old (aHR=3.9, 95% CI: 2.6–5.8; pCONCLUSION

The 4-year incidence rate of hypertension among apparently healthy adult Filipinos is high. Increased age, male sex, family history of hypertension, abdominal obesity, and high normal blood pressure were significantly associated with the development of hypertension.

Objective: To investigate the characteristics of allele frequencies for 9 red blood cell (RBC) blood group systems in the Hui ethnic voluntary blood donor population of Suzhou using real-time fluorescence PCR technology, so as to provide technical support for establishing a RBC blood group genetic database. Methods: PCR-TaqMan technology was employed to perform genotyping detection for 9 RBC blood group systems using 144 samples from Hui voluntary blood donors in Suzhou, collected between October 2023 and August 2024. Results: Blood group allele frequencies among Suzhou Hui voluntary blood donors were distributed as follows: MNS system (M=0.566 0, N=0.434 0; S=0.079 9, s=0.920 1); Lutheran system (Lu =0.003 5, Lu =0.996 5; Au =0.895 8, Au =0.104 2); Kell system (K=0.000 0, k=1.000 0; Kp =0.003 5, Kp =0.996 5; JS =0.000 0, JS =1.000 0); Duffy system (Fy =0.899 3, Fy =0.100 7); Kidd system (JK =0.451 4, JK =0.548 6); Diego system (Di =0.041 7, Di =0.958 3); Yt system (Yt =0.996 5, Yt =0.003 5); Dombrock system (Do =0.128 5, Do =0.871 5); Colton system (Co =1.000 0, Co =0.000 0). The PCR-TaqMan-based RBC blood group genotyping technology successfully completed testing for all samples. Conclusion: The MNS, Lutheran, Duffy, Kidd, Diego, and Dombrock blood group systems in the Suzhou Hui population exhibited polymorphic distribution patterns, whereas the Colton system was monomorphic. Standardized application of PCR-TaqMan technology facilitates the establishment of an RBC blood group genetic database.

Background: The COVID-19 pandemic has placed an extraordinary strain on healthcare systems worldwide, underscoring the need for evidence-based pharmacotherapy and rational use of medicines. Despite the availability of international and national treatment guidelines, notable variations in drug selection and utilization persist across healthcare institutions. Evaluating medication use according to clinical severity is vital for ensuring therapeutic rationality, improving patient outcomes, and optimizing pharmaceutical resource management. Aim: The aim of this study was to assess medication use and associated costs among inpatients diagnosed with COVID-19 at the Mongolia–Japan Hospital of MNUMS and the National Center for Communicable Diseases through ABC analysis Materials and Methods: : A retrospective, document-based study was conducted at the Mongolia-Japan Hospital (MJH) and the National Center for Communicable Diseases (NCCD) in Ulaanbaatar. Medical and pharmacy records of 1,012 inpatients diagnosed with COVID-19 between April 18 and December 31, 2021, were reviewed. Drug utilization was assessed using the ABC analysis method, classifying medicines based on their proportional contribution to total pharmaceutical expenditure. Comparative analyses were performed to identify differences in utilization patterns between hospitals and across clinical severity levels. Results: Of the total pharmaceutical expenditure for COVID-19 treatment, six medicines (4.5% of all drugs) were categorized as Class A, accounting for 69.7% of total costs. Class B included seven medicines (7.0%, 19.5% of total costs), while Class C comprised twenty-six medicines (88.6%, 10.6% of total costs). Remdesivir 100 mg injection, a Class A drug, represented 18.5% of total drug expenditure at MJH (used in 78 patients) and 36.2% at NCCD (used in 133 patients). Overall, approximately 70% of total expenditure was concentrated in a small number of high-cost medicines, indicating potential inefficiencies in pharmaceutical resource utilization. Conclusion This study demonstrates that a limited number of high-cost medicines, particularly Remdesivir, accounted for the majority of COVID-19 treatment expenditures. Strengthening evidence-based prescribing, rational selection, and monitoring of high-cost drugs is essential to enhance resource efficiency, ensure equitable access, and sustain hospital pharmaceutical care systems during pandemic response and beyond.

As a novel form of cell death, ferroptosis is mainly regulated by the accumulation of soluble iron ions in the cytoplasm and the production of lipid peroxides and is closely associated with several diseases, including acute kidney injury, ischemic reperfusion injury, neurodegenerative diseases, and cancer. The term "immunosuppression" refers to various factors that can directly harm immune cells' structure and function and affect the synthesis, release, and biological activity of immune molecules, leading to the insufficient response of the immune system to antigen production, failure to successfully resist the invasion of foreign pathogens, and even organ damage and metabolic disorders. An immunosuppressive phase commonly occurs in the progression of many ferroptosis-related diseases, and ferroptosis can directly inhibit immune cell function. However, the relationship between ferroptosis and immunosuppression has not yet been published due to their complicated interactions in various diseases. Therefore, this review deeply discusses the contribution of ferroptosis to immunosuppression in specific cases. In addition to offering new therapeutic targets for ferroptosis-related diseases, the findings will help clarify the issues on how ferroptosis contributes to immunosuppression.
Ferroptosis/immunology* ; Humans ; Immune Tolerance/immunology* ; Animals ; Immunosuppression Therapy ; Iron/metabolism* ; Neoplasms/immunology*

ChuanWu (CW), the dried mother root of Aconitum carmichaelii Debx., is a well-known traditional Chinese medicine (TCM) recognized for its potent efficacy but inherent toxicity, primarily due to its alkaloid content. Traditional and modern detoxification methods for CW include proper processing, rational compatibility, and specialized decoction techniques, among which honey-boiled CW is particularly distinctive. However, research on the detoxification mechanism of honey-boiled CW remains limited. This study investigated this mechanism by analyzing alkaloid transformation and supramolecular aggregation. Honey-boiled and water-boiled CW preparations were compared. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used to analyze CW alkaloids, specifically diester alkaloids (DDAs), monoester alkaloids (MDAs), and non-esterified diterpenoid alkaloids (NDAs). Transmission electron microscopy was employed to observe and identify supramolecular aggregates in the honey-boiled CW decoction. In vivo absorption of water-boiled, honey-boiled, and NADES-boiled CW was compared. Median lethal dose (LD₅₀) tests assessed toxicity, including hepatotoxicity and nephrotoxicity. In vitro experiments evaluated the safety, anti-inflammatory, and analgesic effects of CW-medicated serum on RAW264.7 cells, with in vivo validation in mice. Results showed that honey promoted the conversion of highly toxic DDAs to less toxic MDAs and prevented MDAs from hydrolyzing into NDAs. Honey-boiled CW formed approximately 250 nm supramolecular aggregates that encapsulated MDAs, inhibiting their conversion to NDAs. These encapsulated MDAs acted as a stable delivery system with higher bioavailability than free benzoylmesaconine. Subsequent mouse experiments confirmed that honey-boiled CW significantly increased the LD₅₀ of CW while reducing hepatotoxicity and nephrotoxicity. Additionally, honey-boiled CW significantly improved cell safety and enhanced anti-inflammatory and analgesic effects. Our findings reveal that honey-boiled CW exhibits a potent detoxification mechanism by influencing alkaloid transformation and facilitating the formation of supramolecular aggregates. This study lays the groundwork for developing detoxification or synergistic strategies within honey-boiled TCM.