ObjectiveBased on whole-animal mass spectrometry imaging technology， spatial metabolomics was used to characterize in situ the metabolic alteration patterns in the lungs and brain of a rat model of lung heat-induced cough and asthma， as well as after treatment with Xiebai San. MethodsNine Sprague-Dawley （SD） rats were randomly divided into a blank group （physiological saline）， a model group （physiological saline）， and a Xiebai San group （9 g·kg^-1）， with three rats in each group. The model group and the Xiebai San group were both induced using lipopolysaccharide-ovalbumin （LPS-OVA） to establish an asthma rat model. After treatment with Xiebai San， the animals were euthanized on day 21 and rapidly frozen in liquid nitrogen to preserve morphology. Whole-animal tissue sections were prepared using a cryomicrotome， and imaging was performed using the Air-flow-assisted Desorption Electrospray Ionization Mass Spectrometry Imaging （AFADESI-MSI） platform. Based on the corresponding optical images， ion data of metabolites from the lung and brain tissues of each group were extracted. Differential metabolites were analyzed using SIMCA and GraphPad Prism 9.0 software. Metabolites were identified using the HMDB （https：//hmdb.ca/） and LipidMAPS^® （https：//www.lipidmaps.org/） databases， and metabolic changes in the lungs and brain were analyzed. ResultsMass spectrometry imaging showed that， after Xiebai San intervention， components such as neoglycyrrhizin and glycyrrhizin from Glycyrrhizae Radix et Rhizoma， as well as palmitamide from Lycii Cortex， were significantly distributed in the lung and brain tissues of rats. Lung analysis indicated that substances with anti-inflammatory effects， such as citric acid， were significantly decreased （P0.01）， while lipid metabolites such as lysophosphatidylethanolamine （LPE 17：1）， LPE （22：4）， and LPE （19：0） （P0.01） were significantly increased， showing a marked inflammatory response in the model group. After Xiebai San intervention， these conditions were notably improved. Analysis of metabolic changes in brain tissue showed that， compared with the blank group， amino acid and fatty acid metabolic pathways in the model group exhibited restricted alterations. Among them， levels of aspartic acid， glutamic acid， fatty acid （FA 18：5）， hydroxy fatty acids （FAHFA 36：0；O）， FA （6：1；O6）， and LPE （18：1） increased， whereas FA （16：0） and FA （20：4） significantly decreased. Administration of Xiebai San improved these metabolic abnormalities in the brain. Systematic analysis of lung and brain metabolic changes in rats with lung heat-induced cough and asthma showed that antioxidant unsaturated phospholipid substances were significantly decreased in the model group， suggesting oxidative stress and inflammation-related lung-brain axis responses after the onset of lung heat-induced cough and asthma. ConclusionUsing whole-animal mass spectrometry imaging combined with spatial metabolomics revealed the in vivo distribution of Xiebai San constituents， characterized the metabolic alterations in the lungs and brain caused by lung heat-induced cough and asthma， and systematically demonstrated the lung-brain axis inflammatory responses and the regulatory effects of Xiebai San. These findings provide valuable information for the study of Chinese medicine in lung heat-induced cough and asthma.

OBJECTIVE To explore the influencing factors for successful detoxification in patients undergoing methadone maintenance therapy. METHODS A retrospective selection of 161 methadone maintenance therapy patients from the South Branch of Zhongshan Second People’s Hospital （including methadone maintenance treatment sites in Shiqi District， Xiqu District， Development Zone of Zhongshan City） from January 1， 2012， to January 1， 2025， was conducted as the study object. Data collected included patients’ sociodemographic information， drug abuse history， laboratory test results， medication records， etc. Patients were divided into the unsuccessful detoxification group and the successful detoxification group based on whether methadone detoxification was achieved. Univariate， univariate Cox regression， and multivariate Cox proportional hazards regression were used for influencing factor analysis， and the Kaplan-Meier method was employed for survival analysis. RESULTS Among the 161 methadone maintenance therapy patients， 96 were in the successful detoxification group and 65 in the unsuccessful detoxification group， yielding a successful detoxification rate of 59.63%. Multivariate Cox proportional hazards regression analysis revealed that age， registered residence status， age at first drug use， and duration of drug abuse were key influencing factors for successful detoxification in methadone maintenance therapy patients （P＜0.05）. Specifically， the successful detoxification rate for patients with Zhongshan local registered residence was 8.364 times higher than that for patients with non-local registered residence； for every 1-year increase in patient age， the successful detoxification rate decreased by 22.7%； for every 1-year increase in age at first drug use， the successful detoxification rate rose by 33.4%； and for every 1-year increase in duration of drug abuse， the successful detoxification rate increased by 33.5%. Survival analysis showed that the successful detoxification rate in the methadone low-dose group （≤30.8 mg） was significantly higher than that in the methadone high-dose group （＞30.8 mg） （P＝0.015）， and the successful detoxification rate in the population with Zhongshan local registered residence was significantly higher than that in those with non-local registered residence （P＜0.001）. CONCLUSIONS Age， registered residence status， age at first drug use， and duration of drug abuse are key influencing factors for successful detoxification in patients undergoing methadone maintenance therapy， and the last methadone dose may be associated with successful detoxification.

ObjectiveBased on whole-animal mass spectrometry imaging technology， spatial metabolomics was used to characterize in situ the metabolic alteration patterns in the lungs and brain of a rat model of lung heat-induced cough and asthma， as well as after treatment with Xiebai San. MethodsNine Sprague-Dawley （SD） rats were randomly divided into a blank group （physiological saline）， a model group （physiological saline）， and a Xiebai San group （9 g·kg^-1）， with three rats in each group. The model group and the Xiebai San group were both induced using lipopolysaccharide-ovalbumin （LPS-OVA） to establish an asthma rat model. After treatment with Xiebai San， the animals were euthanized on day 21 and rapidly frozen in liquid nitrogen to preserve morphology. Whole-animal tissue sections were prepared using a cryomicrotome， and imaging was performed using the Air-flow-assisted Desorption Electrospray Ionization Mass Spectrometry Imaging （AFADESI-MSI） platform. Based on the corresponding optical images， ion data of metabolites from the lung and brain tissues of each group were extracted. Differential metabolites were analyzed using SIMCA and GraphPad Prism 9.0 software. Metabolites were identified using the HMDB （https：//hmdb.ca/） and LipidMAPS^® （https：//www.lipidmaps.org/） databases， and metabolic changes in the lungs and brain were analyzed. ResultsMass spectrometry imaging showed that， after Xiebai San intervention， components such as neoglycyrrhizin and glycyrrhizin from Glycyrrhizae Radix et Rhizoma， as well as palmitamide from Lycii Cortex， were significantly distributed in the lung and brain tissues of rats. Lung analysis indicated that substances with anti-inflammatory effects， such as citric acid， were significantly decreased （P0.01）， while lipid metabolites such as lysophosphatidylethanolamine （LPE 17：1）， LPE （22：4）， and LPE （19：0） （P0.01） were significantly increased， showing a marked inflammatory response in the model group. After Xiebai San intervention， these conditions were notably improved. Analysis of metabolic changes in brain tissue showed that， compared with the blank group， amino acid and fatty acid metabolic pathways in the model group exhibited restricted alterations. Among them， levels of aspartic acid， glutamic acid， fatty acid （FA 18：5）， hydroxy fatty acids （FAHFA 36：0；O）， FA （6：1；O6）， and LPE （18：1） increased， whereas FA （16：0） and FA （20：4） significantly decreased. Administration of Xiebai San improved these metabolic abnormalities in the brain. Systematic analysis of lung and brain metabolic changes in rats with lung heat-induced cough and asthma showed that antioxidant unsaturated phospholipid substances were significantly decreased in the model group， suggesting oxidative stress and inflammation-related lung-brain axis responses after the onset of lung heat-induced cough and asthma. ConclusionUsing whole-animal mass spectrometry imaging combined with spatial metabolomics revealed the in vivo distribution of Xiebai San constituents， characterized the metabolic alterations in the lungs and brain caused by lung heat-induced cough and asthma， and systematically demonstrated the lung-brain axis inflammatory responses and the regulatory effects of Xiebai San. These findings provide valuable information for the study of Chinese medicine in lung heat-induced cough and asthma.

Objective To explore the causal relationship between immune cells and heart failure (HF), and the mediating role of serum metabolites, in order to identify potential biomarkers and therapeutic targets. Methods We employed a two-sample Mendelian randomization (MR) analysis method based on genome-wide association study (GWAS) data, analyzing the direct and indirect effects of 731 types of immune cells and 1 400 metabolites on HF. We selected valid instrumental variables and conducted statistical analyses using R software. The primary analysis was performed using the inverse variance weighted method, supplemented by MR-Egger analysis and weighted median method. The stability of the results was assessed through tests such as Cochran’s Q test. Results Our research found a negative causal relationship between PD-L1 on CD14−CD16+ and HF. Sensitivity analysis supported this result. The reverse MR analysis did not find an effect of HF on PD-L1 on CD14−CD16+, indicating that PD-L1 on CD14−CD16+ might play a unidirectional role in reducing the risk of HF. Further mediation MR analysis showed that PD-L1 on CD14−CD16+ might influence the risk of HF onset by regulating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), with a mediation effect ratio of 6.7%. Conclusion PD-L1 on CD14−CD16+ may reduce the risk of HF by elevating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), which provides a new perspective for understanding the pathogenesis of HF.

OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

To analyze the disease burden of acute lymphoid leukemia(ALL) and its changing trends in China and globally from 1990 to 2021, aiming to provide a theoretical basis for disease prevention, treatment, and policy formulation.

ObjectiveThe Golgi apparatus serves as a central hub in the eukaryotic secretory pathway, responsible for the processing, sorting, and trafficking of proteins and lipids. In mammalian cells, the Golgi typically forms a perinuclear ribbon-like structure composed of laterally connected cisternae stacks.The maintenance of Golgi ribbon structure depends on the balance of membrane flux across multiple intracellular trafficking pathways, yet the specific contributions of distinct trafficking branches to Golgi macroscopic morphology remain elusive. In mammalian cells, the Golgi ribbon is typically organized as a perinuclear, laterally connected structure composed of stacked cisternae, and its integrity is highly dynamic and sensitive to perturbations in membrane trafficking. This study aims to elucidate the role of coat protein complex I (COPI)-mediated retrograde transport in maintaining the Golgi ribbon and to dissect the functional relationship between the transmembrane cargo receptors LEPROT/LEPROTL1 (LEPROTs) and the COPI adaptor GOLPH3. MethodsUsing siRNA interference and gene-deficient cell lines, we selectively perturbed COPI- or adaptor protein complex 1 (AP-1)-mediated trafficking pathways in HeLa cells. To quantitatively evaluate Golgi morphology, we employed a “Golgi Angle”-based measurement to assess its circumferential distribution around the nucleus. The spatial distribution of the Golgi ribbon was quantitatively analyzed using confocal microscopy, while Golgi ultrastructure and vesicle density were examined via transmission electron microscopy. Additionally, the subcellular distribution of COPI components was assessed by immunofluorescence co-localization. ResultsSelective inhibition of COPI retrograde transport significantly induced the circumferential extension of the Golgi ribbon around the nucleus, whereas blocking AP-1-mediated anterograde transport resulted in Golgi compaction, indicating opposing roles. These results suggest that different trafficking branches downstream of ARF1 exert distinct and even antagonistic effects on Golgi morphology. LEPROTs-deficient cells exhibited a Golgi extension phenotype highly consistent with COPI impairment. Furthermore, knockdown of GOLPH3 in a LEPROTs double-knockout background produced a significant additive effect on Golgi extension, suggesting that LEPROTs and GOLPH3 play non-redundant roles in regulating COPI-related trafficking processes. Mechanistically, loss of either LEPROTs or GOLPH3 led to the aberrant accumulation of COPI components at endoplasmic reticulum exit sites, accompanied by a reduction in COPI-like vesicles around the Golgi. This redistribution indicates a defect in COPI recycling between the ER-Golgi interface and the Golgi apparatus. Ultrastructural analysis revealed that Golgi cisternae in defective cells became shorter and thicker while maintaining a stable number of stacks. In parallel, the density of Golgi-associated vesicles was markedly decreased, further supporting an impairment in COPI vesicle formation or budding processes. ConclusionThis study demonstrates that active COPI retrograde transport is a critical factor in restricting the over-connection of the Golgi ribbon and maintaining its compactness. Rather than causing fragmentation, partial disruption of COPI function leads to a distinct morphological outcome characterized by Golgi ribbon extension at the light microscopy level and cisternal remodeling at the ultrastructural level. LEPROTs and GOLPH3 cooperatively promote the recycling and vesiculation of COPI components, thereby imposing a structural constraint on the Golgi periphery. Our findings support a model in which multiple adaptor proteins act in parallel to sustain efficient COPI cycling, thereby maintaining Golgi structural homeostasis. These findings provide new cell biological evidence for the membrane trafficking basis of Golgi morphological homeostasis.

ObjectiveTo explore the mechanisms of Qingchang Wenzhong Decoction （清肠温中方， QWD） in treating ulcerative colitis （UC）. MethodsA total of 100 male C57BL/6J mice were assigned to a pseudo-germ-free group （n=45） and a conventional group （n=55） using a random number table. Pseudo-germ-free model was established by giving antibiotic treatment and subsequently subjected to acute UC induction. After the model was successfully established， the 45 pseudo-germ-free acute UC mice were randomly allocated to a pseudo-germ-free model group， a pseudo-germ-free QWD group， and a pseudo-germ-free mesalazine group， with 15 mice in each group. The 55 conventional mice were randomly divided into a normal control group （n=10）， as well as a conventional model group， a conventional QWD group， and a conventional mesalazine group， with 15 mice in each group. Except for the normal control group， acute UC models were established in all other groups. Mice in the control group received no intervention. From day 32 of the experiment， mice in the pseudo-germ-free QWD group and the conventional QWD group were administered with QWD granules at a dose of 9.71 g/（kg·d） by gavage with deionized water， while those in the pseudo-germ-free mesalazine group and the conventional mesalazine group were given mesalazine enteric-coated tablets at a dose of 151.67 mg/（kg·d） by gavage. Mice in the remaining groups received an equal volume of deionized water once daily for 7 consecutive days. On day 25 of the experiment， six mice were randomly selected from both the pseudo-germ-free group and the conventional group to measure body weight， and fecal samples were collected for 16S rDNA sequencing to compare differences in gut microbiota， including operational taxonomic units （OTUs）， Shannon index， Observed_species index， and phylogenetic diversity （PD whole tree）. On day 39， body weight was measured in all groups， and the disease activity index （DAI） was evaluated. Colon length and colon wet weight were recorded. Histopathological changes in colonic tissues were assessed by hematoxylin and eosin （HE） staining， and histological injury scores were determined. In addition， the expression levels of mucopolysaccharides and mucin 2 （MUC2） in colonic tissues were measured. ResultsOn day 25， there was no significant difference in body weight between the pseudo-germ-free group and the conventional microbiota group （P＞0.05）. Compared to the conventional microbiota group， the pseudo-germ-free group showed significantly reduced OTUs， Shannon index， Observed_species index， and PD whole tree （P＜0.01）. On day 39， compared to the normal control group， mice in the conventional model group showed a significant decrease in the body weight and an increase in DAI， along with increased colon wet weight， shortened colon length， markedly elevated histopathological scores， and reduced expression of mucopolysaccharides and MUC2 （P＜0.01）. In contrast， no significant differences were observed in these parameters in the pseudo-germ-free model group （P＞0.05）. Compared to the conventional model group， the conventional QWD group showed significant improvement in all measured parameters， whereas the conventional mesalazine group showed reductions only in DAI scores and colon wet weight （P＜0.01）. No statistically significant differences were observed among the pseudo-germ-free model group， the pseudo-germ-free QWD group， and the pseudo-germ-free mesalazine group （P＞0.05）. ConclusionQWD may promote the reconstruction of the intestinal mucus barrier by regulating the intestinal flora， thereby exerting a therapeutic effect on acute UC.

Objective To explore the independent risk factors for complicated coronary heart disease (CHD) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) and to construct a risk prediction model. Methods A retrospective study was performed to analyze the clinical data of 308 OSAHS patients who visited Jiangsu Provincial People's Hospital from January 2021 to June 2025. The patients were divided into the CHD group (n=80) and non-CHD group (n=228) according to the presence or absence of complicated CHD. Independent risk factors were identified using univariate analysis and multivariate logistic regression, and a nomogram prediction model was constructed. The model was evaluated using the calibration curve, Hosmer-Lemeshow test, Decision Curve Analysis (DCA) curve, and Receiver Operating Characteristic (ROC) curve. Results The incidence of CHD in OSAHS patients was 25.97%. Age, history of hypertension, oxygen desaturation index (ODI), severe polysomnography (PSG) grade, decreased high-density lipoprotein cholesterol, elevated homocysteine, and elevated troponin I were independent risk factors for OSAHS complicated with CHD (P<0.05). The nomogram model demonstrated good calibration (Hosmer-Lemeshow test, P=0.995), and the DCA curve showed high clinical net benefit. The area under the ROC curve was 0.940 (95% CI: 0.908~0.972), with a sensitivity of 0.842 and a specificity of 0.900. Conclusion Age, history of hypertension, ODI, PSG grade, high-density lipoprotein cholesterol, homocysteine, and troponin I are independent risk factors for CHD in OSAHS patients. The prediction model constructed based on these factors can provide a reliable tool for clinical nurses to early identify high-risk individuals and formulate targeted intervention strategies.

ObjectiveTo explore the mechanisms of Qingchang Wenzhong Decoction （清肠温中方， QWD） in treating ulcerative colitis （UC）. MethodsA total of 100 male C57BL/6J mice were assigned to a pseudo-germ-free group （n=45） and a conventional group （n=55） using a random number table. Pseudo-germ-free model was established by giving antibiotic treatment and subsequently subjected to acute UC induction. After the model was successfully established， the 45 pseudo-germ-free acute UC mice were randomly allocated to a pseudo-germ-free model group， a pseudo-germ-free QWD group， and a pseudo-germ-free mesalazine group， with 15 mice in each group. The 55 conventional mice were randomly divided into a normal control group （n=10）， as well as a conventional model group， a conventional QWD group， and a conventional mesalazine group， with 15 mice in each group. Except for the normal control group， acute UC models were established in all other groups. Mice in the control group received no intervention. From day 32 of the experiment， mice in the pseudo-germ-free QWD group and the conventional QWD group were administered with QWD granules at a dose of 9.71 g/（kg·d） by gavage with deionized water， while those in the pseudo-germ-free mesalazine group and the conventional mesalazine group were given mesalazine enteric-coated tablets at a dose of 151.67 mg/（kg·d） by gavage. Mice in the remaining groups received an equal volume of deionized water once daily for 7 consecutive days. On day 25 of the experiment， six mice were randomly selected from both the pseudo-germ-free group and the conventional group to measure body weight， and fecal samples were collected for 16S rDNA sequencing to compare differences in gut microbiota， including operational taxonomic units （OTUs）， Shannon index， Observed_species index， and phylogenetic diversity （PD whole tree）. On day 39， body weight was measured in all groups， and the disease activity index （DAI） was evaluated. Colon length and colon wet weight were recorded. Histopathological changes in colonic tissues were assessed by hematoxylin and eosin （HE） staining， and histological injury scores were determined. In addition， the expression levels of mucopolysaccharides and mucin 2 （MUC2） in colonic tissues were measured. ResultsOn day 25， there was no significant difference in body weight between the pseudo-germ-free group and the conventional microbiota group （P＞0.05）. Compared to the conventional microbiota group， the pseudo-germ-free group showed significantly reduced OTUs， Shannon index， Observed_species index， and PD whole tree （P＜0.01）. On day 39， compared to the normal control group， mice in the conventional model group showed a significant decrease in the body weight and an increase in DAI， along with increased colon wet weight， shortened colon length， markedly elevated histopathological scores， and reduced expression of mucopolysaccharides and MUC2 （P＜0.01）. In contrast， no significant differences were observed in these parameters in the pseudo-germ-free model group （P＞0.05）. Compared to the conventional model group， the conventional QWD group showed significant improvement in all measured parameters， whereas the conventional mesalazine group showed reductions only in DAI scores and colon wet weight （P＜0.01）. No statistically significant differences were observed among the pseudo-germ-free model group， the pseudo-germ-free QWD group， and the pseudo-germ-free mesalazine group （P＞0.05）. ConclusionQWD may promote the reconstruction of the intestinal mucus barrier by regulating the intestinal flora， thereby exerting a therapeutic effect on acute UC.