OBJECTIVE To evaluate the clinical efficacy of dapagliflozin in patients with pulmonary hypertension associated with left heart disease （PH-LHD） and its effect on prognosis， and to provide evidence for its clinical application. METHODS A total of 135 hospitalized patients with PH-LHD admitted to Wuxi No. 2 People’s Hospital from January 1， 2023 to June 30， 2025 were retrospectively included. According to the treatment regimen， the patients were divided into a control group （74 cases， receiving conventional treatment） and a dapagliflozin group （61 cases， receiving dapagliflozin in addition to conventional treatment）. Blood pressure [systolic blood pressure， diastolic blood pressure， and pulmonary artery systolic pressure （PASP）]， echocardiographic cardiac function parameters [cardiac output， cardiac index， left ventricular ejection fraction （LVEF）， right ventricular ejection fraction （RVEF）， left atrial diameter， and left ventricular wall thickness]， inflammatory factors [interleukin-6 （IL-6） and high-sensitivity C-reactive protein （hs-CRP）]， brain natriuretic peptide （BNP）， and 6-minute walking distance （6MWD） were compared between the two groups before treatment and after 12 weeks of treatment. All-cause mortality and the frequency of rehospitalization due to worsening heart failure during follow-up were also compared. RESULTS After 12 weeks of treatment， systolic blood pressure， diastolic blood pressure， PASP， left atrial diameter， IL-6， hs-CRP， and BNP levels were significantly decreased or shortened in both groups， while cardiac index and 6MWD were significantly increased or prolonged compared with those before treatment （ P ＜0.05）. Cardiac output in the dapagliflozin group was significantly increased compared with that before treatment （ P ＜0.05）. Systolic blood pressure， PASP， left atrial diameter， IL-6， hs-CRP， and BNP levels in the dapagliflozin group were significantly lower or shorter than those in the control group， while cardiac output， cardiac index， and 6MWD were significantly higher or longer than those in the control group （ P ＜0.05）. There were no statistically significant differences in LVEF， RVEF， or left ventricular wall thickness between the two groups （ P ＞0.05）. The median follow-up times in the control group and dapagliflozin group were 17.9 months and 17.3 months， respectively. During follow-up， all-cause mortality in the dapagliflozin group was lower than that i n the control group， but the difference was not statistically significant （ P ＞0.05）； the frequency of rehospitalization due to worsening heart failure was significantly lower than that in the control group （ P ＜0.05）. CONCLUSIONS On the basis of conventional treatment， the addition of dapagliflozin can further reduce pulmonary artery pressure， inflammatory factor levels， and BNP levels in patients with PH-LHD， improve some cardiac function-related parameters and exercise tolerance， and reduce the frequency of rehospitalization due to worsening heart failure.

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

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Transformer models have emerged as pivotal tools within the realm of drug discovery, distinguished by their unique architectural features and exceptional performance in managing intricate data landscapes. Leveraging the innate capabilities of transformer architectures to comprehend intricate hierarchical dependencies inherent in sequential data, these models showcase remarkable efficacy across various tasks, including new drug design and drug target identification. The adaptability of pre-trained transformer-based models renders them indispensable assets for driving data-centric advancements in drug discovery, chemistry, and biology, furnishing a robust framework that expedites innovation and discovery within these domains. Beyond their technical prowess, the success of transformer-based models in drug discovery, chemistry, and biology extends to their interdisciplinary potential, seamlessly combining biological, physical, chemical, and pharmacological insights to bridge gaps across diverse disciplines. This integrative approach not only enhances the depth and breadth of research endeavors but also fosters synergistic collaborations and exchange of ideas among disparate fields. In our review, we elucidate the myriad applications of transformers in drug discovery, as well as chemistry and biology, spanning from protein design and protein engineering, to molecular dynamics (MD), drug target identification, transformer-enabled drug virtual screening (VS), drug lead optimization, drug addiction, small data set challenges, chemical and biological image analysis, chemical language understanding, and single cell data. Finally, we conclude the survey by deliberating on promising trends in transformer models within the context of drug discovery and other sciences.

Transformer models have emerged as pivotal tools within the realm of drug discovery,distinguished by their unique architectural features and exceptional performance in managing intricate data landscapes.Leveraging the innate capabilities of transformer architectures to comprehend intricate hierarchical dependencies inherent in sequential data,these models showcase remarkable efficacy across various tasks,including new drug design and drug target identification.The adaptability of pre-trained trans-former-based models renders them indispensable assets for driving data-centric advancements in drug discovery,chemistry,and biology,furnishing a robust framework that expedites innovation and dis-covery within these domains.Beyond their technical prowess,the success of transformer-based models in drug discovery,chemistry,and biology extends to their interdisciplinary potential,seamlessly combining biological,physical,chemical,and pharmacological insights to bridge gaps across diverse disciplines.This integrative approach not only enhances the depth and breadth of research endeavors but also fosters synergistic collaborations and exchange of ideas among disparate fields.In our review,we elucidate the myriad applications of transformers in drug discovery,as well as chemistry and biology,spanning from protein design and protein engineering,to molecular dynamics(MD),drug target iden-tification,transformer-enabled drug virtual screening(VS),drug lead optimization,drug addiction,small data set challenges,chemical and biological image analysis,chemical language understanding,and single cell data.Finally,we conclude the survey by deliberating on promising trends in transformer models within the context of drug discovery and other sciences.

Drug quality problems seriously threaten the life and health of patients,drug quality problems handling is an important part of pharmaceutical management in medical institutions,and strengthening the management of drug quality problems in medical institutions can provide a strong guarantee for drug safety of patients.This standard was compiled by the Pharmaceutical Affairs Commission of the Chinese Hospital Association,and the process included problems identification,framework development,manuscript writing,opinions gathering,expert argumentation and deliberation,and standards development.The standard regulates the basic requirements,coping strategies,quality control and continuous improvement of drug quality problems handling in medical institutions.This article elaborates on the methods and contents of formulating standards for drug quality problems handling,to pro-vide reference and inspiration for medical institutions to carry out drug quality problems handling.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

Objective To explore the effect of hypoxic exercise on Irisin secretion of obese rats with a palmitic acid-induced lipid accumulation in L6 myotubes and a high-fat diet-induced model.Methods L6 myotubes were treated with 750 μmol/L palmitic acid to induce lipid accumulation and subsequently divided into four groups of normoxia(N),exercise(E),hypoxia(H),and hypoxic exer-cise(HE).Hypoxic conditions(1%O2)were used to simulate a low-oxygen environment,while AICAR stimulation was applied to the E and HE groups to mimic exercise.Eighty 3-week-old Sprague-Dawley rats were fed a high-fat diet for 16 weeks to establish an obesity model.Fifty obese rats that met the criteria were then selected and randomly assigned according to their body weight into five groups of normoxia-sedentary(NC),normoxia-exercise(NE),hypoxia-sedentary(HC),high-liv-ing high-training(HH),and low-living high-training(LH),each of 10.The hypoxic environment was set at 13.6%O2(simulating 3,500 m altitude).Then the NE,HH and LH groups performed daily one-hour treadmill training(NE:20 m/min;HH and LH:16 m/min),5 days/week for 4 weeks.After the intervention,the body composition was measured using dual-energy X-ray absorptiometry(DEXA),while Irisin concentrations in cell culture media and rat serum were determined by using the enzyme-linked immunosorbent assay.Moreover,fibronectin type Ⅲ domain-containing 5(FNDC5)mRNA expression in L6 cells and rat skeletal muscle was measured by quantitative polymerase chain reaction(qPCR),while FNDC5 and silent information regulator 1-peroxisome proliferators-activated re-ceptor γ coactivator lalpha(SIRT1-PGC-1α)pathway proteins were analyzed using Western blotting.Results(1)Cell experiments:①Compared with the N group,there were significantly higher Irisin lev-els in the culture medium of the E,H,and HE groups(P<0.01,P<0.05),as well as elevated FNDC5 mRNA and protein expression in the E and HE groups(P<0.05,P<0.01).Moreover,the Iri-sin concentration and FNDC5 protein levels of group HE were significantly higher than group E(P<0.05).②Compared with group N,significantly increased SIRT1 and PGC-1α protein expression was observed in groups E and HE(P<0.05,P<0.01).(2)Animal experiments:①Compared with the NC group,body weight and fat mass were significantly lower in the NE,LH,and HH groups(P<0.01),with further reductions observed in the HH group compared with the NE group(P<0.05).② Com-pared with group NC,groups NE,LH,and HH exhibited higher serum Irisin levels and increased FNDC5 mRNA and protein expression in skeletal muscle(P<0.05,P<0.01).Furthermore,FNDC5 pro-tein expression of the HH group was significantly higher than the NE group(P<0.05).③ Compared with the NC group,SIRT1 and PGC-1α protein levels were significantly upregulated in the NE,LH,and HH groups(P<0.05,P<0.01).Conclusion Hypoxic exercise effectively alleviates obesity,reduces body weight and fat accumulation in high-fat diet-induced obese rats,and enhances FNDC5 expres-sion and Irisin secretion,which may be mediated through activation of the SIRT1-PGC-1α signaling pathway.Moreover,among the different hypoxic exercise modalities,the"high-living high-training"protocol appears to have greater benefits in promoting FNDC5/Irisin expression and facilitating weight and fat reduction in obese rats.

Preeclampsia (PE) is a severe gestational disorder characterized by hypertension and proteinuria, with a subset of cases exhibiting an immune-driven phenotype marked by placental overexpression of proinflammatory cytokines and chronic inflammatory damage, profoundly impacting fetal development. To elucidate the pathophysiology of this PE subtype, we established an inflammation-driven PE mouse model via lipopolysaccharide (LPS) intraperitoneal injection, systematically evaluating histopathological changes in maternal heart, liver, lung, kidney, and placenta, and integrating transcriptomic profiling to uncover molecular mechanisms. LPS administration robustly induced maternal hypertension and proteinuria, hallmarks of PE, without significantly altering organ or fetal weights. Histological analyses revealed pronounced inflammatory damage in the maternal lung, kidney, and placenta, with the lung exhibiting the most severe pathology, characterized by inflammatory cell infiltration, alveolar wall thickening, and interstitial edema-challenging the conventional focus on placental and renal primacy in PE. Placental labyrinth and junctional zones displayed extensive structural disruption and necrosis, indicating functional impairment. Transcriptomic analysis identified 27 inflammation-related genes consistently upregulated across tissues, with protein-protein interaction networks pinpointing Il1β, Il6, Ccl5, Ccl2, Cxcl10, Tlr2, and Icam1 as hub genes. Quantitative PCR validation confirmed Tlr2 as a central regulator, evidenced by significant upregulation of Tlr2 in lung, kidney, and placenta of LPS-induced PE mice, while Cxcl10 exhibited placenta-specific upregulation, suggesting a synergistic inflammatory axis in placental pathology. These findings highlight the lung as a critical, yet underappreciated, target in inflammation-driven PE, reframe the multi-organ inflammatory landscape of the disease, and nominate Tlr2 and Cxcl10 as potential diagnostic biomarkers and therapeutic targets, offering new avenues for precision intervention in PE.
Animals ; Female ; Pregnancy ; Mice ; Pre-Eclampsia/genetics* ; Inflammation ; Lipopolysaccharides/adverse effects* ; Disease Models, Animal ; Transcriptome ; Placenta/pathology* ; Phenotype

The antidepressant activity and molecular mechanisms of Yueju Wan volatile oil were investigated. The Yueju Wan volatile oil was extracted by using supercritical CO_2. Gas chromatography-mass spectrometry(GC-MS) combined with network pharmacology identified 28 chemical constituents in Yueju Wan volatile oil, primarily terpenes and lactones. A total of 123 overlapping targets were associated with depression, including core targets of interleukin-1β(IL-1β), signal transducer and activator of transcription 3(STAT3), and caspase-3(CASP3). These targets were mainly involved in the prolactin, advanced glycation end products/receptor(AGE/RAGE), and phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) signaling pathways. A reserpine-induced depression mouse model was established to evaluate the therapeutic effects and mechanisms of Yueju Wan volatile oil. The effects of Yueju Wan volatile oil on depression-like behavior in mice were evaluated by analyzing body mass, body temperature index, tail suspension immobility time, forced swimming immobility time, and sucrose preference. Hematoxylin-eosin(HE) staining revealed neuronal protection of Yueju Wan volatile oil in the brain of mice. Enzyme-linked immunosorbent assay(ELISA) and Western blot were employed to detect the protein expression of AGEs, IL-1β, phosphorylated PI3K(p-PI3K), Akt, phosphorylated Akt(p-Akt), nuclear factor κB(NF-κB), and brain-derived neurotrophic factor(BDNF). Behavioral evaluation showed that Yueju Wan volatile oil could effectively control the decline of body mass and body temperature of depressed mice, reduce tail suspension and swimming immobility time, and enhance their preference for sucrose. Histopathological examination showed that Yueju Wan volatile oil could alleviate the neuronal damage in CA1 and dentate gyrus(DG) of the hippocampus of mice. ELISA and Western blot results showed that Yueju Wan volatile oil could significantly increase the protein expression levels of PI3K, Akt, and BDNF and significantly decrease the protein expression levels of AGEs, IL-1β, p-PI3K, p-Akt, and NF-κB in the hippocampus of mice. Furthermore, the p-PI3K/PI3K and p-Akt/Akt ratios were significantly decreased at medium and high doses. These findings suggest that the aromatherapy of Yueju Wan volatile oil can significantly improve reserpine-induced depression-like behavior in mice, which may be related to reducing the expression of neuronal membrane protein AGEs, reducing the phosphorylation levels of PI3K and Akt, inhibiting NF-κB entry into the nucleus, and alleviating the release of pro-inflammatory factors and nerve injury.
Animals ; Antidepressive Agents/chemistry* ; Mice ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/immunology* ; Oils, Volatile/chemistry* ; Male ; Drugs, Chinese Herbal/chemistry* ; Signal Transduction/drug effects* ; Depression/metabolism* ; Glycation End Products, Advanced/immunology* ; Humans