The present study aimed to establish an LC-MS/MS method for the quantification of tiamulin in minipig plasma and to further conduct a pharmacokinetic comparison of different formulations. The plasma samples were extracted with acetonitrile (meloxicam as internal standard), separated on a C18 column, and quantified by multiple reaction monitoring mode (ESI+). Sanyuan minipigs were used as experimental animals. Plasma samples were collected after intravenous injection (10 mg/kg) and intragastric administration (20 mg/kg). The method showed good linearity, with intra- and inter-batch RSD of 1.00%–8.13% and RE within ±15%. The extraction recovery, matrix effect and stability of the analytical methods met the relevant requirements. Tiamulin fumarate active pharmaceutical ingredient was intravenously administered, with c0 of about (4383.73±2676.78) ng/mL, AUC0-t of about (4803.50±965.68) h·ng/mL, t1/2 of about (4.66±1.68) h, and CL of about (2.14±0.46) L/(kg·h). Three tiamulin formulations were intragastrically administered, with cmax of (552.00±328.55), (545.00±136.97) and (590.60±237.02) ng/mL, tmax of (1.47±0.68), (0.69±0.75) and (0.72±0.72) h, and F of 24.85%, 15.28% and 16.97%, respectively. The validated method meets the requirements for biological sample analysis and is applicable for the pharmacokinetic evaluation of tiamulin formulations in minipigs.

Objective To analyze Chinese and English publications pertaining to Oncomelania hupensis control from 2005 to 2024, so as to decipher the research status and hotspots of O. hupensis control. Methods Chinese and English publications pertaining to O. hupensis control from 2005 to 2024 were retrieved in the Web of Science Core Collection Database and China National Knowledge Infrastructure. The annual number of publications was analyzed from 2005 to 2024, and the author and institution cooperation networks were mapped using the software CiteSpace 6.3.1. Keywords were extracted from publications to map the co-occurrence, burst and timeline of keywords to identify the research hotspots of O. hupensis control. Results A total of 158 English publications and 771 Chinese publications were included for bibliometric analyses. The overall output of English publications was relatively small from 2005 to 2024, the annual average publication was 7.90 publications. Parasites & Vectors was the most productive journal by the number of publications (21 publications). The three most productive authors included Li Shizhu (24 publications), Zhou Xiaonong (13 publications), and Yang Kun (12 publications), and the three most productive institutions included Chinese Center for Disease Control and Prevention (49 publications), the WHO (27 publications), and Fudan University (25 publications). The annual average number of Chinese publications was high from 2005 to 2015 (57.73 publications), and reduced to 15.11 publications during the period from 2016 to 2024, with Chinese Journal of Schistosomiasis Control as the most productive journal (241 publications). The three most productive authors included Wang Wanxian (18 publications), Sun Qixiang (16 publications), and Dai Jianrong (16 publications), and the three most productive institutions included Jiangsu Institute of Parasitic Diseases (55 publications), Chinese Center for Disease Control and Prevention (47 publications), and Hubei Uni-versity (38 publications). Among the 158 English publications, molluscicidal effect, climate change, geographic information, biological control, machine learning were current research hotspots, and the Yangtze River and elimination were emerging research hotspots. Among the 771 Chinese publications, molluscicidal effect, niclosamide, comprehensive management, molluscicide, effectiveness evaluation, marshland, and endophyte were current research hotspots, and the future research hotspots shifted to molluscicidal effect and pyriclobenzuron. Conclusions Limited attention is paid to the research on O. hupensis control across the world. The Yangtze River, elimination, molluscicidal effect, and pyriclobenzuron may be future research hotspots. High attention is recommended to be paid to the research on O. hupensis control, and development of diverse approaches for O. hupensis control is of urgent needs. We should continue to attach importance to the control research of O. hupensis and strengthen the exploration of diverse snail extermination and control methods.

This paper summarizes professor TU Jinwen's clinical experience in treating cancer-related insomnia （CRI） based on different qi and fire. It is believed that the pathogenesis of CRI can be divided into three stages. At the initial stage， qi movement is constrained， while the strong fire begins to stir， and the sovereign fire is unsettled， when qi is abundant， but the fire is not excessive. For this， Sanhua Jieyu Anshen Decoction （三花解郁安神汤） is suggested， which can move qi and vent constraint， clear and diffuse strong fire， calm the heart and spirit. At the progressive stage， strong fire becomes intense and burning， and qi transformation weakens， with toxin fire harassing the spirit. This is the stage where both qi and fire are excessive， for which Huanglian Jiedu Anshen Decoction （黄连解毒安神汤） can be used to clear and dissipate strong fire， drain fire and resolve toxin， clear heart and calm spirit. At the terminal stage， strong fire subsides， and consumption of qi damages healthy qi， with failure of nourishment of heart spirit， when both qi and fire deplete. Correspondingly， Erren Yangxin Anshen Decoction （二仁养心安神汤） is used to boost qi and nourish yin， restore interaction between the heart and the kidney， nourish the heart and calm spirit.

Objective To explore the predictive value of artificial intelligence (AI)-based lung nodule CT quantitative analysis for the invasion degree of lung adenocarcinoma spectrum lesions. Methods According to the invasion degree of lung adenocarcinoma spectrum lesions, patients with surgically and pathologically confirmed lung adenocarcinoma spectrum lesions from January to June 2023 in Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University were retrospectively collected and divided into a non-invasive group and an invasive group, including atypical adenomatous hyperplasia, adenocarcinoma in situ, and minimally invasive adenocarcinoma patients in the non-invasive group, and invasive adenocarcinoma patients in the invasive group. All enrolled patients underwent chest CT before surgery, and then the lung nodules were quantitatively analyzed using an AI-based computer-aided diagnosis system to compare the related quantitative parameters of lung nodules that have been surgically removed and pathologically confirmed as lung adenocarcinoma spectrum lesions between the two groups. The relationship between various CT quantitative features and the invasion degree of lung adenocarcinoma spectrum lesions was analyzed. Results A total of 149 patients (149 lesions) were included, including 42 males and 107 females, aged 29-81 (56.35±10.75) years. There were 72 patients in the non-invasive group and 77 patients in the invasive group. Statistical differences were observed between the two groups in long diameter, short diameter, volume, surface area, mass, maximum cross-sectional area, 3D long diameter, maximum CT value, minimum CT value, average CT value, entropy, kurtosis, skewness, malignancy probability and other indicators (P<0.05). Multivariate binary logistic regression analysis showed that long diameter [OR=1.687, 95%CI (1.364, 2.085), P<0.001], average CT value [OR=1.006, 95%CI (1.002, 1.009), P=0.002], and malignancy probability [OR=1.034, 95%CI (1.005, 1.063), P=0.020] were independent risk factors for the invasion degree of lung adenocarcinoma. The predictive model combining the above parameters demonstrated optimal performance, with an area under the receiver operating characteristic curve of 0.951, sensitivity of 0.818, and specificity of 0.972. Using a Nomogram to quantify the three independent risk factors, the cross-validation was performed to evaluate the stability of the model, and the average C-index of cross-validation was 0.950, with each fold C-index >0.75, indicating that the prediction performance of the model was stable, and the calibration curve and decision curve indicated good predictive performance. Conclusion The visualization prediction model constructed by AI-based quantitative analysis of lung nodules in CT demonstrates significant discriminative effectiveness in the assessment of invasiveness in lung adenocarcinoma spectrum lesions. This visualization prediction model can provide a quantitative decision-making basis for the preoperative identification of the degree of invasiveness in lung adenocarcinoma spectrum lesions.

ObjectiveTo investigate the efficacy and safety of simplified diagnosis and treatment strategies and regimens in the treatment of patients with human immunodeficiency virus （HIV）/hepatitis C virus （HCV） co-infection. MethodsThis multicenter prospective real-world study was conducted among 198 patients with HIV/HCV co-infection who received hepatitis C treatment in 10 designated primary hospitals for hepatitis C in Yuxi， China from July 2023 to June 2024， and according to whether genotype detection was performed， they were divided into genotype detection group with 122 patients and non-genotype detection group with 76 patients. The patients were observed in terms of sustained virologic response at 12 weeks （SVR12）， safety， and liver biochemical parameters. Propensity score matching was used to match the two cohorts， using caliper matching （caliper value = 0.02） at a ratio of 1∶1. The independent-samples t test or the Wilcoxon signed-rank test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between groups. ResultsAmong the 122 patients in the genotype detection group， 63.11% （77/122） had genotype 3， while the non-genotype detection group had 76 patients； both groups achieved an SVR12 rate of 100%. From baseline to 12 weeks after treatment， both groups had a significant increase in the serum level of albumin， significant reductions in the serum levels of total bilirubin， alanine aminotransferase， aspartate aminotransferase， and alpha-fetoprotein， and a significant reduction in FibroScan value （all P<0.05）. A total of 54 patients （27.27%） experienced at least one adverse reaction， and anemia was the most common adverse reaction （38 patients， 19.19%）， with an incidence rate of 50.00% （33/66） in patients with liver cirrhosis. HIV viral load remained <50 IU/mL before and after treatment， and there was no significant change in CD4⁺ T lymphocyte count after treatment （Z=-0.969， P=0.202）. Compared with the genotype detection group， the non-genotype detection group had a significantly shorter time from positive HCV RNA testing to treatment initiation （4±2 days vs 19±4 days， t=5.321， P<0.05） and significantly lower testing costs （618±97 yuan vs 789±129 yuan， t=3.661， P<0.05）. ConclusionFor patients with HIV/HCV co-infection， the simplified diagnosis and treatment strategies can achieve a relatively high SVR12 rate， improve biochemical indicators， and effectively reduce time cost and economic burden， with a favorable safety profile.

Objective:To investigate the therapeutic effect of platelet-rich plasma(PRP)combined with Xianling Gubao Capsule on rats with osteoarthritis(OA)and the changes in the levels of related factors.Methods:Anterior cruciate ligament transection was performed to establish a rat model of OA,and after modeling,the rats were randomly divided into control group,model group,Xianling Gubao Capsule group,PRP group,and Xianling Gubao Capsule+PRP group,with 10 rats in each group.After intervention,ELISA was used to measure the serum levels of IL-1β and TNF-α;knee articular cartilage was collected,and qPCR and Western blot were used to measure the mRNA and protein expression levels of MMP3,MMP13,Col2,Aggrecan,and p-p38;Micro-CT was used to assess the changes in bones around the knee joint;HE staining and SF staining were used to observe the changes in knee articular cartilage.Results:ELISA showed that PRP combined with Xianling Gubao Capsule significantly reduced the serum levels of the inflammatory factors such as IL-1β and TNF-α(P<0.05).The results of qPCR and Western blot showed that PRP combined with Xianling Gubao Capsule significantly reduced the expression levels of MMP3,MMP13,and p-p38 and increased the expression levels of Col2 and Ag-grecan in knee articular cartilage(P<0.05).Micro-CT,HE staining,and SF staining showed a certain degree of improvement in knee articular cartilage degeneration in the Xianling Gubao Capsule+PRP group(P<0.05).Conclusion:PRP combined with Xianling Gubao Capsule exerts a therapeutic effect on rats with OA,possibly by regulating the p38MAPK signaling pathway.

Hepatic ischemia-reperfusion injury(IRI)is a pathological phenomenon that commonly occurs during liver surgery and transplantation.It leads to serious tissue damage and affects liver function.The mechanisms behind IRI are complex,involving oxida-tive stress,inflammatory responses,and calcium homeostasis disorder.Recently,scientists have paid more attention to the role of endo-plasmic reticulum stress(ERS)in IRI.ERS activates three classical signaling pathways,PERK,IRE1,and ATF6,through the unfolded protein response(UPR),aiming to preliminarily restore endoplasmic reticulum homeostasis and protect cells.However,if the stress re-sponse is excessive or persistent,ERS can activate apoptosis signaling pathways,such as CHOP and Bax/Bak,worsening cell injury.Additionally,ERS is closely related to other cellular stress responses,such as autophagy and oxidative stress,which jointly affect the survival and death of hepatocytes.Regulation of ERS,especially interventions targeting the three UPR pathways,is considered as a po-tential therapeutic pathway for alleviating hepatic IRI.Pharmacological interventions,such as 4-phenylbutyric acid and taurocholic acid,and gene therapies,such as knocking out PERK or IRE1,have shown positive effects in protecting liver function while inhibiting ERS.This paper reviews the mechanism of action of ERS in hepatic IRI,focuses on the specific roles of the three UPR pathways and their potential as therapeutic targets,and explores the future of re-lated therapeutic strategies.

Objective:To explore the therapeutic effect of compound Kuijie Ankang Decoction on ulcerative colitis (UC) model mice by non targeted metabonomics; To explore its mechanism.Compound Kuijie Ankang.Methods:The mice were randomly divided into blank control group, model group, Kuijie Ankang Decoction group and sulfasalazine group, with 12 mice in each group. Except the blank control group, the other groups were given 1.5% DSS solution for free drinking to prepare UC model. After successful modeling, Kuijie Ankang Decoction group was intragastrically administered with compound Kuijie Ankang Decoction of 9.68 g/kg, sulfasalazine group was intragastrically administered with sulfasalazine capsule suspension of 320 mg/kg, model group and blank control group were intragastrically administered with equal volume of purified water, once a day, for 7 consecutive days. The body mass and disease activity index (DAI) score of mice were measured. ELISA was used to measure the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) in the colon tissue of mice; the protein expressions of Claudin-1 and Zo-1 in colon tissue were detected by immunofluorescence method. HE staining was used to observe the pathological changes in the colon, and UHPLC-OE-MS technology was used to analyze the endogenous metabolite structure of mouse colon tissue, differential metabolites and related metabolic pathways were screened.Results:Compared with the model group, the colon length in Kuijie Ankang Decoction group and sulfasalazine group increased ( P<0.01), the DAI score decreased ( P<0.01), the levels of TNF-α, IL-1β and IL-6 in colon tissue decreased ( P<0.01), the level of IL-10 increased ( P<0.01), and the average optical density of Claudin-1 and Zo-1 protein increased ( P<0.01 or P<0.05). Metabolomics analysis identified 26 potential differential metabolites, including nicotinamide adenine dinucleotide, guanine, gamma aminobutyric acid, and thiamine, affecting 26 key metabolic pathways, including lysine biosynthesis, thiamine metabolism, cysteine and methionine metabolism. Conclusion:Kuaijie Ankang Decoction may improve metabolites such as Gamma aminobutyric acid and thiamine through metabolic pathways such as lysine biosynthesis to alleviate inflammatory reactions, thereby exerting therapeutic effects on ulcerative colitis in mice.

Drug-induced liver injury(DILI)is a common adverse drug reaction in clinical practice,which can lead to acute liver failure and even death in severe cases.In recent years,with the continuous introduction of new drugs and the expansion of their usage,the incidence and mortality rates of DILI have shown an upward trend,posing significant challenges to public health and clinical treatment.Macrophages,as a crucial component of the innate immune system,exhibit high plasticity and heterogeneity.They can polarize into pro-inflammatory M1 type or anti-inflammatory M2 type in response to microenvironmental signals.Research has demonstrated that macrophage polarization plays a central regulatory role in the occurrence and progression of DILI by influencing various processes such as inflammatory responses,cell apoptosis,and tissue repair.This review focuses on elucidating the regulatory mechanisms and roles of macrophage polarization in DILI,providing a theoretical framework for developing precise immunotherapeutic strategies.