ObjectiveTo investigate whether Huanglian Jiedutang （HLJD） and its major active constituents （geniposide， baicalin， and berberine） can inhibit the inflammatory response of BV2 cells under lipopolysaccharide （LPS） stimulation via the high-mobility group protein B1 （HMGB1）/Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway， and to explore differences in therapeutic efficacy among the three monomers， their combined formula， and HLJD under equal content ratios. MethodsBV2 microglial cells were used as the primary experimental model. Cell viability was assessed using the cell counting kit-8 （CCK-8） method to examine the effects of different concentrations of dimethyl sulfoxide （DMSO， 0.8%， 0.4%， 0.2%， 0.1%， and 0.05%） on cell viability. IncuCyte was employed to monitor the growth of cells under different concentrations of HLJD （200， 100， 50， 25， 12.5， 6.25 mg·L^-1）. Nitric oxide （NO） assay was used to screen the optimal HLJD concentration. High-performance liquid chromatography （HPLC） determined the content of geniposide， baicalin， and berberine in HLJD， and experimental groups were subsequently established according to the relative proportions of these constituents. CCK-8 assay evaluated cell viability under different treatments. Enzyme-linked immunosorbent assay （ELISA） measured levels of inflammatory factors （TNF-α， IL-1β， IL-6， IL-10） in the supernatant. Flow cytometry assessed the effects of treatments on M1-type polarization of BV2 cells. Western blot determined the expression levels of HMGB1， TLR4， and NF-κB-related proteins. ResultsCompared with the blank group， DMSO at concentrations ≤0.2% did not affect cell viability within 48 h. BV2 cell growth plateaued at 24 h after treatment with 200 mg·L^-1 HLJD. Under stimulation with 2 mg·L^-1 LPS， this concentration of HLJD effectively reduced NO release， and 6 h pre-treatment had a stronger inhibitory effect on NO than direct administration. HPLC results showed that 1 mg of HLJD freeze-dried powder contained approximately 24 μg of geniposide， 15 μg of baicalin， and 30 μg of berberine. Based on these ratios， experimental groups were blank， LPS （2 mg·L^-1）， HLJD （200 mg·L^-1）， monomer combination， geniposide （4.8 mg·L^-1）， baicalin （3 mg·L^-1）， and berberine （6 mg·L^-1）. The monomer combination group consisted of all three active constituents dissolved together. LPS and HLJD or its active constituents did not affect cell viability compared with the blank group. LPS significantly increased TNF-α， IL-1β， IL-6， and IL-10 in the supernatant （P<0.01）. HLJD and its active constituents significantly reduced pro-inflammatory factors TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01） while upregulating anti-inflammatory IL-10 （P<0.01）， with the monomer combination showing the strongest effect （P<0.05， P<0.01）. Compared with the blank group， LPS significantly increased the proportion of CD80⁺CD86⁺ （M1-type） BV2 cells （P<0.01）. HLJD and its constituents partially inhibited M1 polarization （P<0.05， P<0.01）， with the monomer combination exhibiting the most pronounced effect （P<0.05， P<0.01）. Compared with the blank group， LPS upregulated HMGB1， TLR4， and NF-κB-related proteins （P<0.01）， whereas HLJD and its active constituents significantly reduced their expression （P<0.05， P<0.01）， with the monomer combination having the strongest regulatory effect （P<0.05， P<0.01）. ConclusionHLJD and its major active constituents （geniposide， baicalin， berberine） can inhibit LPS-induced inflammatory responses in BV2 cells. The combination of the three active constituents demonstrates the most potent anti-inflammatory effect， significantly attenuating M1-type polarization of BV2 cells via the HMGB1/TLR4/NF-κB signaling pathway.

Background: Malignant pleural effusion (MPE), a common complication of advanced cancers, is associated with poor prognosis and reduced quality of life. Although host–tumor interactions are known to drive MPE development, the associated immune dynamics during disease progression remain unclear. Using a Lewis lung carcinoma-induced MPE model in C57BL/6JNidfc mice, we systematically evaluated general parameters and immune cell changes at two-day intervals throughout disease progression. Results: The day of Lewis lung carcinoma cell injection into the pleural space was designated as day 0. By day 10 post-injection (p.i.), MPE-bearing mice exhibited ~ 10% body weight loss, marking the experimental endpoint. Pleural tumor mass and pleural effusion volume were minimal up to day 4 p.i. but increased sharply from day 6 onward.CD45⁺ immune cell counts rose over time, and days 6, 8, and 10 p.i. marked key stages of MPE progression. On day 6, B cells, T cells, and natural killer cells, but not macrophages and neutrophils, increased significantly compared to earlier timepoints. By day 8, all immune cell subsets except T cells exceeded day 6 levels, and at day 10, natural killer cell numbers declined while others continued to increase. Besides, the numbers of CD8⁺ T cells, Th1 cells, regulatory T cells, and M2 macrophages progressively increased from day 6 to 10. Based on these data, days 6 and 10 were defined as early and advanced MPE stages, respectively, with distinct immune phenotypes. In advanced MPE, CD8⁺ T cells displayed reduced IFN-γ, TNF-α, Granzyme B, Perforin, FasL, and Ki-67, but upregulated PD-1 and CTLA-4 relative to early stage. Similarly, Th1 cells showed decreased IFN-γ, TNF-α, and IL-2 production along with reduced Ki-67 expression. Advanced-stage M2 macrophages exhibited lower MHC-II levels and impaired phagocytosis, but higher PD-L1 and IL-10 production, while neutrophils showed reduced TNF-α release and phagocytic activity. Conclusions Our findings characterize the temporal immune dynamics associated with MPE progression in a mouse model, revealing a transition from an early immunostimulatory state to a late immunosuppressive state. This study enhances our understanding of MPE immunopathogenesis and provides a foundation for developing precise, stagespecific therapeutic strategies.

Objective To investigate the epidemiological characteristics and changing trend of typhus in Shaanxi Province from 2005 to 2023 to provide a scientific basis for its prevention and control. Methods Excel 2007, SPSS 25.0, Joinpoint 4.9.1.0, and Geoda 1.6 were used for data collection and statistical analysis. Super Map was used for data visualization to describe the changing characteristics of the disease. Results A total of 394 typhus cases were reported in Shaanxi Province from 2005 to 2023. The average annual incidence of typhus was 0.054/100 000, showing a dynamic fluctuation trend(AAPC=-3.3, t=-0.3, P>0.05). The cases were mainly concentrated in Baoji, Hanzhong and Xi′an, accounting for 78.68%. The incidence peak was from May to October, accounting for 64.21% of annual incidence. The epidemic season was from May to October and December. The incidence of the disease was concentrated in the 40-69 age group, accounting for 58.88%, and the sex was 1.07:1. The main occupation was farmers, accounting for 72.08%. The median time from onset to diagnosis was 7 days. Global spatial autocorrelation analysis showed that there were significant spatial autocorrelations in 11 years from 2005 to 2023(P<0.05). Local spatial autocorrelation analysis detected a total of 43“high-high”clustering areas, mainly concentrated in Baoji City. Conclusions The overall incidence of typhus in Shaanxi Province showed a dynamic fluctuation trend, with notable seasonal and regional aggregation. The incidence of typhus was higher in middle-aged and elderly people in rural areas. Surveillance should be strengthened in typhus endemic areas in summer and autumn, and health education should be conducted for key population to form good health habits and reduce the incidence of typhus.

" Lijie and yellowish sweating" originates from the chapter on stroke and arthralgia diseases in Synopsis of Golden Chamber. Later generations typically interpret it as yellow fluid oozing from painful joints, a characteristic manifestation of arthralgia. In Western medicine, Lijie corresponds to diseases such as gouty arthritis, with its primary clinical manifestations being redness, swelling, heat, and painful joints, most often without yellow fluid discharge. Therefore, the interpretation of " Lijie and yellowish sweating" contradicts the clinical manifestations often observed in this disease. Thus, this article reinterprets the meaning of " Lijie and yellowish sweating" from the pathogenesis of " sweat exposure to water, as if water harms the heart" , combined with the viewpoints of other medical practitioners. Determining the meaning of " yellowish sweating" is crucial for understanding the pathogenesis of arthralgia and clarifying the relationship between arthralgia and yellowish sweating. ZHANG Zhongjing mentioned arthralgia and " yellowish sweating" together, not to differentiate between the two diseases but to emphasize the common pathogenesis of the two, namely, the cold and dampness injuring the heart, blood, and vessels. This paper proposes a new explanation of " Lijie and yellowish sweating" , which suggests that " yellowish sweating" is not confined to the joints but can be found all over the body. The pathogenesis of " Lijie and yellowish sweating" lies in the insufficiency of the liver and kidney and exogenous water dampness, leading to disharmony between nutrient qi and defensive qi and between yin and yang. Primary treatment should harmonize yingfen and weifen, as well as tonify and replenish the liver and kidney. The clinical selection of medicines can be considered Guizhi Decotion, a type of formula. The pathogenesis of " Lijie and yellowish sweating" is complex, and clinical treatment should be comprehensively considered to achieve the best therapeutic effect.

As the number of patients with compromised immune function increases and fungal resistance develops, so does the risk of contracting deadly fungi in humans. Both fungi and humans are eukaryotes, so identifying unique targets for antifungal drug development is difficult. In addition, the existing antifungal drugs are limited by toxicity, drug interaction and drug resistance in practical application, which leads to the increasing incidence and fatal rate of fungal infections. Therefore, it is urgent to develop new antifungal drugs. The semi-synthetic technology using microbial fermentation products from natural sources as lead compounds has become the most used method in structural modification of antifungal drugs due to its advantages of few reaction steps and easy operation. This paper will introduce the current status of natural antifungal drugs in clinical use, as well as the latest progress in the research and development of new semi-synthetic antifungal drugs, and summarize their mechanism of action, structural modifications, advantages and disadvantages, so as to provide reference for the subsequent development of new antifungal drugs.

[Objective] To establish a cryopreservation protocol for small-volume (≤1 mL) red blood cells (RBCs) and to evaluate the reactivity and stability of blood group antigens after cryopreservation, so as to explore its potential application in immunohematology reference laboratories. [Methods] Small-volume RBCs were cryopreserved for 120 days, followed by thawing and deglycerolization to restore the RBC components. The quality of the RBCs was assessed. Serum antibodies were serially diluted and reacted with RBCs before and after cryopreservation, and agglutination scores were recorded to quantitatively evaluate the reactivity and stability of blood group antigens such as Rh, Duffy, Lewis, Kidd, M, and H. Flow cytometry was used to analyze the percentage and mean fluorescence intensity of ABO antigen expression on RBCs before and after cryopreservation to assess the usability of cryopreserved RBCs in flow immunophenotyping and blood group subtype studies. [Results] The hemolysis rate of thawed and deglycerolized RBCs was (0.27±0.10)%, with a supernatant free hemoglobin level of (0.52±0.14) g/L, and the RBC recovery rate was (69.12±7.91)%. The direct antiglobulin test (DAT) was negative for all thawed RBCs. There was no difference in the reactivity of blood group antigens before and after cryopreservation, and no difference in the percentage and mean fluorescence intensity of A and B antigen expression on RBCs before and after cryopreservation. [Conclusion] The small-volume RBC cryopreservation protocol can be applied to immunohematology analysis in reference laboratories and is expected to be widely used in blood group identification, antibody screening, identification, and blood group-related research.

Objective:To compare the efficacy and safety of the gastrointestinal endoscopic super minimally invasive surgery (eSMIS) and the laparoscopic minimally invasive procedure (LS) for the treatment of gastric glomus tumors(GGT).Methods:This study retrospectively included 15 patients with GGT who underwent eSMIS at the First Medical Center of Chinese PLA General Hospital from May 2014 to May 2024. Data on demographic characteristics, surgical indexes, efficacy evaluation indexes, postoperative medical disposition, health economics indexes and postoperative laboratory indexes were collected and analyzed, the patients were followed up for survival outcomes and the postoperative quality of life, efficacy and safety of the two groups were compared.Results:The amount of bleeding in the eSMIS group was lower than that in the LS group: 1.25 (0, 3.75) ml vs. 41.56 (10.00, 50.00) ml, and the surgical cost in the eSMIS group was lower than that in the LS group: 10 792.87 (8 424.90, 12 730.30) yuan vs. 21 773.06 (19 940.60, 24 843.10) yuan, there were statistical differences ( P<0.05). The surgical efficacy, postoperative laboratory indicators and medical treatment convenience between the two groups had no statistical differences ( P>0.05). Conclusions:In the choice of surgical procedures for the treatment of GGT, eSMIS is superior to LS in terms of bleeding and surgical cost, and not inferior to LS in other indicators. This suggested that the treatment of GGT with eSMIS is feasible, safe and effective.

Objective:This study investigated the independent risk factors for lymph node metastasis（LNM）in high-risk prostate cancer（HRPCa）patients undergoing robot-assisted radical prostatectomy（RARP），and constructed a nomogram model based on clinical data to improve the accuracy and clinical practicality of preoperative prediction of LNM.Methods:A retrospective analysis was conducted on the clinical data of 218 HRPCa patients who received RARP treatment at the First Medical Center of the PLA General Hospital from January 2020 to March 2025 as the modeling group. The age of the modeling group was（66.91±6.94）years old. 75 cases（34.40%）had a history of smoking，and 48 cases（22.02%）had a history of drinking. There were a body mass index（BMI）of 25.55（23.58，27.00）kg/m 2，a total prostate-specific antigen（tPSA）of 20.59（10.42，30.61）ng/ml，a free prostate-specific antigen（fPSA）of 1.87（1.04，3.26）ng/ml，a prostate volume（PV）of（41.19±21.00）ml，a prostate-specific antigen density（PSAD）of 0.52（0.30，0.84）ng/ml 2. Among the patients，60 cases（27.52%）had a preoperative biopsy Gleason score >8，and the percentage of positive biopsy cores（PPBC）was 50%（31%，80%）. Thirty-one patients（14.22%）were staged clinically as >T 2c. The diagnostic criteria for high-risk prostate cancer（HRPCa）were defined as meeting any one of the following：PSA >20 ng/ml，Gleason score on prostate biopsy ≥8，or clinical stage ≥T 3. Among the 218 patients in the modeling cohort，67 cases（30.73%）met two of the criteria，and 7 cases（3.21%）met all three criteria. All 218 patients underwent RARP，and based on postoperative pathology，they were divided into the LNM group and the non-LNM group. The relationship between the number of diagnostic criteria met and the occurrence of LNM was analyzed. An external validation cohort included 42 HRPCa patients who underwent RARP at the Third，Fifth Medical Centers of the PLA General Hospital between January 2023 and May 2025. Their mean age was（66.79±5.92）years. Eighteen patients（42.86%）had a smoking history，and nine（21.43%）had a history of alcohol consumption. The median BMI was 26.00（23.80，27.13）kg/m 2. The median tPSA level was 17.34（8.97，27.30）ng/ml. The median fPSA was 1.51（0.83，2.52）ng/ml，and the median PV was（35.57 ± 15.25）ml. The median PSAD was 0.57（0.23，0.87）ng/ml 2，and the median PPBC was 58%（36%，71%）. Three patients（7.14%）had a clinical stage >T 2c，and 12 patients（28.57%）had a Gleason score >8 on preoperative biopsy. Univariate and multivariate binary logistic regression analyses were used to identify independent risk factors for LNM，and a nomogram model was constructed based on these factors. The predictive performance of the model was evaluated using receiver operating characteristic（ROC）curves and calibration plots，and the model was validated in the external cohort. Result:According to postoperative pathology，45 patients were classified into the LNM group，and 173 into the non-LNM group. The probability of LNM increased proportionally with the number of diagnostic criteria met for HRPCa（meeting two criteria： OR = 4.762，95% CI 2.323-9.761， P < 0.01；meeting three criteria： OR = 10.667，95% CI 2.187-52.025， P=0.003）. Binary logistic regression analysis revealed that age（ OR=0.913，95% CI 0.859-0.971， P = 0.004），tPSA（ OR=1.039，95% CI 1.018-1.061， P<0.01），PPBC（ OR = 5.656，95% CI 1.101-29.056， P = 0.038），and clinical T stage（T 2c stage： OR=2.945，95% CI 0.888-9.769， P=0.077；>T 2c stage OR = 18.351，95% CI 4.790-70.306， P < 0.01）were independent risk factors for postoperative LNM in HRPCa patients after RARP. The ROC curve of the nomogram model based on these factors showed an area under the curve（AUC）of 0.853（95% CI 0.790-0.917）. In the external validation cohort，the nomogram achieved an AUC of 0.743（95% CI 0.556-0.929）. The calibration plots demonstrated good agreement between the predicted probabilities and actual observations. Conclusions:Age，tPSA，PPBC，and clinical T stage were independent predictors of postoperative LNM in HRPCa patients undergoing RARP. The greater the number of HRPCa diagnostic criteria met，the higher the likelihood of postoperative LNM. The nomogram developed in this study could effectively predict the risk of LNM in HRPCa patients after RARP.

Objective:To assess the application value of one-hour post-load glucose (1hPG) for detecting prediabetes among individuals with high risk of type 2 diabetes mellitus (T2DM).Methods:The study was conducted between August 2023 and January 2024, and individuals with a high risk of T2DM were invited to receive an oral glucose tolerance test (OGTT), structural questionnaires, physical measurements, and other biochemical examinations. The fasting, one-, and two-hour glucose and insulin were tested. According to the 1hPG cut point on hyperglycemia suggested by International Diabetes Federation (IDF), normal glucose tolerance (NGT) and prediabetes were further divided into two subgroups, respectively, i.e., NGT with 1hPG<8.6 mmol/L (NGT-1hPG-normal), NGT with 1hPG≥8.6 mmol/L (NGT-1hPG-high), prediabetes with 1hPG<8.6 mmol/L (PDM-1hPG-normal), and prediabetes with 1hPG≥8.6 mmol/L (PDM-1hPG-high). The insulin release curve was drawn by the groups as above. Insulin resistance was evaluated by homeostasis model assessment for insulin resistance (HOMA-IR), and β-cell secretory function was evaluated by homeostasis model assessment for β cell function (HOMA-β)/HOMA-IR. Spearman rank correlation analysis was used to calculate the correlation coefficients among 1hPG, 2hPG and HOMA indices, and Steiger′s Z test was used to compare the difference between two correlation coefficients. Receiver operating characteristics (ROC) curves and area under the curve (AUC) were used to assess the accuracy of 1hPG for detecting prediabetes. Results:A total of 2 469 subjects consisting of 1 485 men (60.1%) and 984 (39.9%) women, with a mean age of (45.76±6.20) years, of which 1 844 (74.7%) had 1hPG≥8.6 mmol/L. The prevalence of 1hPG≥8.6 mmol/L was 46.8%, 93.0% and 99.8% in individuals with NGT, prediabetes and newly diagnosed T2DM, respectively ( χ 2=763.78, P<0.001). The insulin release curve showed that insulin secretion increased rapidly in subjects with NGT-1hPG-high, and peaked at one hour, then decreased rapidly, with a significantly higher level of one- and two-hour insulin than those with NGT-1hPG-normal ( P<0.001). Compared to individuals with NGT-1hPG-normal, the counterparts with NGT-1hPG-high exhibited higher HOMA-IR and lower adjusted HOMA-β ( P<0.001). Spearman rank correlation analysis showed that the correlation coefficient of 1hPG with HOMA-IR was similar to the correlation coefficient of 2hPG with HOMA-IR (0.493 vs. 0.480, P=0.550), while the correlation of 1hPG with adjusted HOMA-β was significantly stronger than that of 2hPG (-0.692 vs. -0.587, P<0.001). Excluding patients with T2DM, according to the cut point recommended by IDF, the AUC of 1hPG≥8.6 mmol/L for detecting prediabetes was 0.731 (95% CI: 0.714-0.748), and the sensitivity and specificity were 0.930 and 0.532, respectively, with the kappa value of 0.45. Conclusion:1hPG is closely related to insulin resistance and islet function, and there′s substantial value for individuals with a high risk of T2DM to detect prediabetes by using the 1hPG cut points recommended by IDF.

Objective:To assess the effects of allergens on interleukin-18 (IL-18), IL-18 binding protein a (IL-18BPa), and IL-18 receptor α (IL-18Rα) expression levels in different monocyte subtypes of the peripheral blood samples of allergic asthma (AA) patients, and the correlations between the percentage of IL-18 +classical monocytes and plasma levels of pro-inflammatory cytokines. Methods:A cross-sectional study. Blood samples were collected from 28 healthy controls and 33 patients experiencing acute attack of AA based on a positive skin prick test of Henan Provincial People′s Hospital from February 2023 to April 2024. Flow cytometry was used to assess the effects of allergens on IL-18, IL-18BPa, and IL-18Rα expression levels in the classical, intermediate, and non-classical monocytes of the peripheral blood samples of AA patients. Kruskal-Wallis test and Pairwise test were used to analyze statistical significance between groups. Plasma tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) levels were estimated using Bioplex assays. Pearson correlation test was used to determine the association between the percentage of IL-18 +classical monocytes and the plasma levels of IL-1β and TNF-α. Results:Compared with healthy controls, the percentages of classical and non-classical monocytes in the peripheral blood of AA patients were reduced by 20.2% ( Z=-3.89, P<0.001) and 45.8% ( Z=-4.01, P<0.001), respectively. Allergens increased the percentages of classical, intermediate, and non-classical monocytes in AA patients in vitro by 13.1%-61.5% (all P<0.05). Compared with healthy controls, the percentages of IL-18 expression in classical monocytes of AA patients was elevated by 1.08-fold ( Z=-6.40, P<0.001), whereas the percentages of IL-18 expression in intermediate and non-classical monocytes were reduced by 52.7% ( Z=-6.40, P<0.001) and 3.23% ( Z=-3.13, P=0.001), respectively. Allergens upregulated IL-18 expression by 16.4%-67.8% in the classical and intermediate monocytes of AA patients (all P<0.05). Compared with healthy controls, IL-18BPa expression level was lower in the three monocyte subtypes of AA patients (all P<0.05). However, allergens upregulated IL-18BPa expression by 8.9% and 13.3% in the classical monocytes (both P<0.05). Compared with healthy controls, IL-18Rα expression was elevated by 1.29-fold in the classical monocytes of AA patients ( Z=-6.40, P<0.001). Allergens upregulated IL-18Rα expression by 17.6%-39.2% in the three monocyte subtypes of AA patients (all P<0.05). Plasma levels of IL-1β and TNF-α in the AA patients were increased compared to those in healthy controls (all P<0.001), and correlated with the percentage of IL-18 +classical monocytes ( r=0.451, 0.714; both P<0.05). Conclusions:Allergens may participate in the inflammatory response of AA by inducing the differentiation of monocytes and the expression levels of IL-18, IL-18BPa and IL-18Rα in different blood monocytes subtypes. Classical monocytes are the potential source of elevated plasma IL-18 level in AA patients.