ObjectiveTo explore the potential mechanism of Xiaoqinglongtang（XQL） in the prevention and treatment of high altitude pulmonary edema（HAPE） by network pharmacology， molecular docking， and molecular dynamics simulation， and to verify it by in vivo animal model. MethodsIn this study， the active ingredients， drug targets， and HAPE-related targets of XQL were collected from BATMAN-TCM， GeneCards， and Online Mendelian Inheritance in Man（OMIM） databases. The protein-protein interaction（PPI） network was constructed by using intersection targets， and the core targets were screened and visualized by Cytoscape software. Functional annotation and pathway analysis of the intersection targets were performed by gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） functional enrichment. AutoDock and GROMACS were used to evaluate the binding ability of active ingredients to key targets. In the experimental verification part， a mouse model of HAPE induced by hypobaric hypoxia（simulated 6 000 m altitude for 48 h） was established. The control effect was evaluated by hematoxylin-eosin（HE） staining， lung tissue water content， lung tissue wet/dry weight ratio， real-time quantitative polymerase chain reaction（Real-time PCR） detection of gene expression levels， and immunohistochemistry and Western blot detection of key protein expression. ResultsA total of 355 active ingredients of XQL， 2 142 targets， 716 HAPE-related targets， and 236 intersection targets were obtained by network pharmacology analysis. Key core targets such as interleukin （IL）-6， tumor necrosis factor （TNF）， protein kinase B1 （Akt1）， and hypoxia-inducible factor-1α （HIF-1α） were screened. The results of GO analysis of common targets involved 738 biological processes（BP）， 72 cellular components（CC）， and 135 molecular functions（MF）. KEGG analysis effectively enriched two important signaling pathways： Phosphoinositol 3-kinase （PI3K）/Akt and HIF-1α. The results of molecular docking and molecular dynamics simulation showed that the screened active ingredients had good binding ability with key targets. In the HAPE model induced by hypobaric hypoxia（6 000 m， 48 h）， the lung tissue water content， lung tissue wet/dry weight ratio， and pathological injury score of the model group were significantly increased（P<0.01）， accompanied by exudation of a large number of red blood cells in the alveoli and alveolar interstitium， a significant increase in inflammatory cells， a significant widening of the alveolar septum， and mutual fusion between the alveoli. The XQL administration group significantly improved the above pathological changes（P<0.01）. The results of inflammatory factor expression showed that compared with the control group， the model group showed significantly up-regulated expression of TNF-α， IL-6， and IL-1β in the lung tissue（P<0.01）. Compared with the model group， the XQL administration group had significantly decreased expression of inflammatory factors（P<0.05， P<0.01）. The mRNA expression of key pathway related genes PI3K， Akt1， mammalian target of rapamycin（mTOR）， and HIF-1α was significantly increased in the model group（P<0.01）， and decreased in a concentration-dependent manner after XQL administration（P<0.05， P<0.01）. The expression levels of key proteins PI3K， phosphorylation（p）-PI3K， Akt1， p-Akt1， mTOR， p-mTOR， and HIF-1α in lung tissue were analyzed by immunohistochemistry and Western blot. Compared with the blank group， the model group showed increased expression of key proteins（P<0.05， P<0.01）. Compared with the model group， the XQL administration group exhibited decreased expression of key proteins（P<0.05， P<0.01）. ConclusionXQL can reduce lung inflammation and improve HAPE. The mechanism may be related to the regulation of PI3K/Akt/mTOR and HIF-1α pathways. This study provides a new idea and a theoretical basis for the treatment of HAPE with XQL.

ObjectiveTo explore the potential mechanism of Xiaoqinglongtang（XQL） in the prevention and treatment of high altitude pulmonary edema（HAPE） by network pharmacology， molecular docking， and molecular dynamics simulation， and to verify it by in vivo animal model. MethodsIn this study， the active ingredients， drug targets， and HAPE-related targets of XQL were collected from BATMAN-TCM， GeneCards， and Online Mendelian Inheritance in Man（OMIM） databases. The protein-protein interaction（PPI） network was constructed by using intersection targets， and the core targets were screened and visualized by Cytoscape software. Functional annotation and pathway analysis of the intersection targets were performed by gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） functional enrichment. AutoDock and GROMACS were used to evaluate the binding ability of active ingredients to key targets. In the experimental verification part， a mouse model of HAPE induced by hypobaric hypoxia（simulated 6 000 m altitude for 48 h） was established. The control effect was evaluated by hematoxylin-eosin（HE） staining， lung tissue water content， lung tissue wet/dry weight ratio， real-time quantitative polymerase chain reaction（Real-time PCR） detection of gene expression levels， and immunohistochemistry and Western blot detection of key protein expression. ResultsA total of 355 active ingredients of XQL， 2 142 targets， 716 HAPE-related targets， and 236 intersection targets were obtained by network pharmacology analysis. Key core targets such as interleukin （IL）-6， tumor necrosis factor （TNF）， protein kinase B1 （Akt1）， and hypoxia-inducible factor-1α （HIF-1α） were screened. The results of GO analysis of common targets involved 738 biological processes（BP）， 72 cellular components（CC）， and 135 molecular functions（MF）. KEGG analysis effectively enriched two important signaling pathways： Phosphoinositol 3-kinase （PI3K）/Akt and HIF-1α. The results of molecular docking and molecular dynamics simulation showed that the screened active ingredients had good binding ability with key targets. In the HAPE model induced by hypobaric hypoxia（6 000 m， 48 h）， the lung tissue water content， lung tissue wet/dry weight ratio， and pathological injury score of the model group were significantly increased（P<0.01）， accompanied by exudation of a large number of red blood cells in the alveoli and alveolar interstitium， a significant increase in inflammatory cells， a significant widening of the alveolar septum， and mutual fusion between the alveoli. The XQL administration group significantly improved the above pathological changes（P<0.01）. The results of inflammatory factor expression showed that compared with the control group， the model group showed significantly up-regulated expression of TNF-α， IL-6， and IL-1β in the lung tissue（P<0.01）. Compared with the model group， the XQL administration group had significantly decreased expression of inflammatory factors（P<0.05， P<0.01）. The mRNA expression of key pathway related genes PI3K， Akt1， mammalian target of rapamycin（mTOR）， and HIF-1α was significantly increased in the model group（P<0.01）， and decreased in a concentration-dependent manner after XQL administration（P<0.05， P<0.01）. The expression levels of key proteins PI3K， phosphorylation（p）-PI3K， Akt1， p-Akt1， mTOR， p-mTOR， and HIF-1α in lung tissue were analyzed by immunohistochemistry and Western blot. Compared with the blank group， the model group showed increased expression of key proteins（P<0.05， P<0.01）. Compared with the model group， the XQL administration group exhibited decreased expression of key proteins（P<0.05， P<0.01）. ConclusionXQL can reduce lung inflammation and improve HAPE. The mechanism may be related to the regulation of PI3K/Akt/mTOR and HIF-1α pathways. This study provides a new idea and a theoretical basis for the treatment of HAPE with XQL.

ObjectiveTo evaluate the comprehensive intervention effects of Huangqin Qingre Chubi Capsule （黄芩清热除痹胶囊， HQC） on self-perception of patients （SPP） and immune inflammation in patients with rheumatoid arthritis （RA）， and to explore its potential mechanisms. MethodsClinical data of 452 RA patients were retrospectively collected. Patients were divided into a control group （274 cases）， treated with conventional western medicine， and an observation group （178 cases）， treated with HQC for at least 2 weeks in addition to conventional western medicine. The treatment duration was 2 weeks for both groups. Propensity score matching （PSM） was performed at a ratio of 1∶1 to match patients between groups. SPP including the Chinese version of the short form-36 health survey （SF-36）， self-rating anxiety scale （SAS）， self-rating depression scale （SDS）， visual analog scale （VAS）， and Chinese patient-reported index for rheumatoid arthritis （CPRI-RA）， as well as immune inflammatory indicators， including erythrocyte sedimentation rate （ESR）， high-sensitivity C-reactive protein （hs-CRP）， rheumatoid factor （RF）， anti-cyclic citrullinated peptide antibody （anti-CCP）， interleukin-6 （IL-6）， immunoglobulin A （IgA）， immunoglobulin G （IgG）， immunoglobulin M （IgM）， complement C3， and complement C4， were collected before and after treatment. Spearman correlation analysis was used to assess the relationships between SPP and immune inflammatory indicators. Logistic regression， association rule analysis， and mediation analysis were performed to evaluate the effects and potential pathways of HQC on SPP and immune inflammatory indicators. Network pharmacology was applied to identify the active components and core targets of HQC in the treatment of RA， followed by molecular docking verification. In cell experiments， cells were divided into normal group， model group， 20% medicated serum group， and 80 nmol/L control group. Human synovial fibroblasts （FLS） were cultured with complete medium in the normal group， while human rheumatoid arthritis fibroblast-like synoviocytes （RA-FLS） were cultured in the model group. In the 20% medicated serum group， RA-FLS were cultured with medium containing 20% HQC-medicated serum， and in the 80 nmol/L control group， RA-FLS were cultured with complete medium containing 80 nmol/L methotrexate suspension. After 48 h of culture， cell viability was detected by cell counting kit-8 （CCK-8） assay. Levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and interleukin-10 （IL-10） in the cell supernatant were measured by enzyme-linked immunosorbent assay （ELISA）. Protein levels of matrix metalloproteinase 9 （MMP9）， transcription factor AP-1 subunit （JUN）， vascular endothelial growth factor A （VEGFA）， and C-X-C motif chemokine ligand 8 （CXCL8） were detected by Western Blot， and cell migration ability was evaluated using Transwell assay. ResultsAfter PSM， 178 cases were included in each group. After treatment， SF-36 scores increased， while scores of SAS， SDS， VAS and CPRI-RA， levels of ESR， hs-CRP， IL-6， complement C3， and complement C4 levels decreased in both groups； IgG and IgM levels were also reduced in the observation group （P＜0.05）. Physical functioning （correlation coefficient -0.19， P＜0.05） and social functioning （correlation coefficient -0.18， P＜0.05） of SF-36 were negatively correlated with hs-CRP， while VAS score was positively correlated with hs-CRP （correlation coefficient 0.19， P＜0.05）. HQC showed high associations with improvements in multiple indicators of SPP and immune inflammatory， and acted as a protective factor for the improvement of several SPP； hs-CRP and ESR played partial mediating roles in the improvement of SPP induced by HQC （P＜0.05）. Network pharmacology analysis identified baicalein， quercetin， α1-sitosterol， β-sitosterol， stigmasterol， baicalin， and crocetin as the core active components， and JUN， IL-6， VEGFA， MMP9， IL-1β， and CXCL8 as the core targets. Molecular docking results showed strong binding affinities of quercetin with VEGFA， JUN， MMP9， IL-6， and IL-1β， of baicalin with VEGFA and MMP9， and of wogonin with CXCL8. Cell experiments demonstrated that HQC and methotrexate inhibited RA-FLS viability and migration， reduced levels of IL-1β， IL-6， and IL-8， decreased protein levels of MMP9， JUN， VEGFA， and CXCL8， and increased IL-10 levels （P＜0.05）. ConclusionHQC can improve SPP in RA by regulating immune inflammatory responses. Its mechanism may be related to multi-pathway and multi-target inhibition of synovial cell inflammation and migration.

Background: This study was performed to characterize the incidence, costs, and risk factors associated with renal and cardiovascular adverse outcomes following primary percutaneous coronary intervention (pPCI) in patients with ST-elevation myocardial infarction (STEMI). Methods: Patients with STEMI who underwent pPCI using iso-osmolar contrast were enrolled at 39 centers. The incidence of acute kidney injury (AKI) and major adverse renal and cardiovascular events (MARCE) was analyzed, as well as inpatient costs. Logistic regression analysis was performed to identify risk factors. Results: Among 2,293 patients, the incidence of AKI and MARCE within 72 hours post-pPCI was 4.14% (n = 95) and 4.40% (n = 101), respectively. AKI and/or MARCE were associated with systolic blood pressure (AKI: odds ratio [OR], 1.009; 95% confidence interval [CI], 1.000–1.018), hypertension (AKI: OR, 1.815; 95% CI, 1.133–2.906; MARCE: OR, 1.760;95% CI, 1.118–2.769), anterior wall infarction (AKI: OR, 1.895; 95% CI, 1.196–3.004; MARCE:OR, 1.939; 95% CI, 1.240–3.032), Killip class (AKI: OR, 1.465; 95% CI, 1.117–1.922; MARCE:OR, 1.467; 95% CI, 1.131–1.903), and serum creatinine (SCr; MARCE: OR, 1.006; 95% CI, 1.000–1.012). Hospitalization costs for patients with STEMI who developed AKI or MARCE were significantly higher than for those without AKI (9,595 ± 5,795 vs. 8,279 ± 3,872 USD, P = 0.003) or without MARCE (9,890 ± 5,616 vs. 8,255 ± 3,859 USD, P < 0.001). Conclusions In patients with STEMI undergoing pPCI with iso-osmolar contrast, the incidence of AKI and MARCE was associated with higher hospitalization costs. Systolic blood pressure, hypertension, anterior wall infarction, Killip class, and SCr were identified as risk factors for these outcomes.

Intra-abdominal Hernia with Bowel Obstruction Triggering Multi-organ Failure: The Role of Preoperative Enteritis This report details the clinical course of a 41-year-old male who developed fulminant multiple organ dysfunction syndrome following emergency surgery for a strangulated intra-abdominal hernia. Preoperative manifestations, including diarrhea and marked leukocytosis, pointed towards an underlying infectious enteritis. We posited that surgical release of the obstructed, ischemic bowel segment precipitated a massive systemic influx of endotoxins and inflammatory mediators, triggering septic shock and rapid sequential organ failure. This case underscored the critical need to suspect concomitant gastrointestinal infection in patients presenting with mechanical bowel obstruction accompanied by infectious signs. Aggressive perioperative sepsis management encompassing early empiric antimicrobial therapy, vigilant hemodynamic monitoring, and preparedness for advanced organ support is essential to mitigate this severe complication.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Objective To establish and internally validate a predictive model for poorly differentiated adenocarcinoma based on CT imaging and tumor marker results. Methods Patients with solid and partially solid lung nodules who underwent lung nodule surgery at the Department of Thoracic Surgery, the Affiliated Brain Hospital of Nanjing Medical University in 2023 were selected and randomly divided into a training set and a validation set at a ratio of 7:3. Patients' CT features, including average density value, maximum diameter, pleural indentation sign, and bronchial inflation sign, as well as patient tumor marker results, were collected. Based on postoperative pathological results, patients were divided into a poorly differentiated adenocarcinoma group and a non-poorly differentiated adenocarcinoma group. Univariate analysis and logistic regression analysis were performed on the training set to establish the predictive model. The receiver operating characteristic (ROC) curve was used to evaluate the model's discriminability, the calibration curve to assess the model's consistency, and the decision curve to evaluate the clinical value of the model, which was then validated in the validation set. Results A total of 299 patients were included, with 103 males and 196 females, with a median age of 57.00 (51.00, 67.25) years. There were 211 patients in the training set and 88 patients in the validation set. Multivariate analysis showed that carcinoembryonic antigen (CEA) value [OR=1.476, 95%CI (1.184, 1.983), P=0.002], cytokeratin 19 fragment antigen (CYFRA21-1) value [OR=1.388, 95%CI (1.084, 1.993), P=0.035], maximum tumor diameter [OR=6.233, 95%CI (1.069, 15.415), P=0.017], and average density [OR=1.083, 95%CI (1.020, 1.194), P=0.040] were independent risk factors for solid and partially solid lung nodules as poorly differentiated adenocarcinoma. Based on this, a predictive model was constructed with an area under the ROC curve of 0.896 [95%CI (0.810, 0.982)], a maximum Youden index corresponding cut-off value of 0.103, sensitivity of 0.750, and specificity of 0.936. Using the Bootstrap method for 1000 samplings, the calibration curve predicted probability was consistent with actual risk. Decision curve analysis indicated positive benefits across all prediction probabilities, demonstrating good clinical value. Conclusion For patients with solid and partially solid lung nodules, preoperative use of CT to measure tumor average density value and maximum diameter, combined with tumor markers CEA and CYFRA21-1 values, can effectively predict whether it is poorly differentiated adenocarcinoma, allowing for early intervention.

The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

OBJECTIVE To establish management index system for rational drug use of key monitoring drugs， and provide reference for the management of key monitoring drugs in the hospitals. METHODS First， the management index system for rational drug use of key monitoring drugs was drafted by collecting the evidence from related medical literature. Next， using a modified Delphi method， twenty experienced experts from the fields of pharmacy， medical practice， healthcare insurance， and finance were selected to participate in two rounds of questionnaire consultations. Based on the expert enthusiasm coefficient， authority coefficient， degree of opinion concentration， and degree of coordination， the final indicators were determined to establish a management index system for rational drug use of key monitored drugs in medical institutions. RESULTS The expert enthusiasm coefficients reached 100% in both rounds of consultation. In first-level， second-level and third-level indicators， the authority coefficients of experts were 0.89， 0.86 and 0.87， and coordination coefficients of the experts in importance score were 0.300 （P＜ 0.05）， 0.125 （P＜0.05） and 0.139 （P＜0.05）， respectively. The average score for the importance of all indicators reached over 3.5， in which the full score ratio ranged from 35% to 100%. Except that the variation coefficient of a third-level indicator “number of specifications purchased for key monitored drugs” was 0.26， the variation coefficients of rest indicators were less than or equal to 0.25. Based on the results of expert consultation， final version of the management index system established in this study， including two first-level indicators （drug procurement and use， and rational drug use）， five second-level indicators （such as the accessibility， cost-effectiveness） and twenty third-level indicators （such as the number of specifications purchased for key monitored drugs， the increase in the cost of key monitored drugs）. CONCLUSIONS The management index system established in this study possesses high reliability and strong operability， and may provide a reference for the management of key monitoring drugs in the hospitals.

Objective To investigate the global burden of visceral leishmaniasis (VL) from 1990 to 2021 and predict the trends in the burden of VL from 2022 to 2035, so as to provide insights into global VL prevention and control. Methods The global age-standardized incidence, prevalence, mortality and disability-adjusted life years (DALYs) rates of VL and their 95% uncertainty intervals (UI) were captured from the Global Burden of Disease Study 2021 (GBD 2021) data resources. The trends in the global burden of VL were evaluated with average annual percent change (AAPC) and 95% confidence interval (CI) from 1990 to 2021, and gender-, age-, country-, geographical area- and socio-demographic index (SDI)-stratified burdens of VL were analyzed. The trends in the global burden of VL were projected with a Bayesian age-period-cohort (BAPC) model from 2022 to 2035, and the associations of age-standardized incidence, prevalence, mortality, and DALYs rates of VL with SDI levels were examined with a smoothing spline model. Results The global age-standardized incidence [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)], prevalence [AAPC = -0.06%, 95% CI: (-0.06%, -0.06%)], mortality [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)] and DALYs rates of VL [AAPC = -2.38%, 95% CI: (-2.44%, -2.33%)] all appeared a tendency towards a decline from 1990 to 2021, and the highest age-standardized incidence [2.55/10⁵, 95% UI: (1.49/10⁵, 4.07/10⁵)], prevalence [0.64/10⁵, 95% UI: (0.37/10⁵, 1.02/10⁵)], mortality [0.51/10⁵, 95% UI: (0, 1.80/10⁵)] and DALYs rates of VL [33.81/10⁵, 95% UI: (0.06/10⁵, 124.09/10⁵)] were seen in tropical Latin America in 2021. The global age-standardized incidence and prevalence of VL were both higher among men [0.57/10⁵, 95% UI: (0.45/10⁵, 0.72/10⁵); 0.14/10⁵, 95% UI: (0.11/10⁵, 0.18/10⁵)] than among women [0.27/10⁵, 95% UI: (0.21/10⁵, 0.33/10⁵); 0.06/10⁵, 95% UI: (0.05/10⁵, 0.08/10⁵)], and the highest mortality of VL was found among children under 5 years of age [0.24/10⁵, 95% UI: (0.08/10⁵, 0.66/10⁵)]. The age-standardized incidence (r = -0.483, P < 0.001), prevalence (r = -0.483, P < 0.001), mortality (r = -0.511, P < 0.001) and DALYs rates of VL (r = -0.514, P < 0.001) correlated negatively with SDI levels from 1990 to 2021. In addition, the global burden of VL was projected with the BAPC model to appear a tendency towards a decline from 2022 to 2035, and the age-standardized incidence, prevalence, mortality and DALYs rates were projected to be reduced to 0.11/10⁵, 0.03/10⁵, 0.02/10⁵ and 1.44/10⁵ in 2035, respectively. Conclusions Although the global burden of VL appeared an overall tendency towards a decline from 1990 to 2021, the burden of VL showed a tendency towards a rise in Central Asia and western sub-Saharan African areas. The age-standardized incidence and prevalence rates of VL were relatively higher among men, and the age-standardized mortality of VL was relatively higher among children under 5 years of age. The global burden of VL was projected to continue to decline from 2022 to 2035.