OBJECTIVE To provide a reference for the pharmaceutical care of a patient with type 2 diabetes mellitus （T2DM） and limb-girdle muscular dystrophy （LGMD） who developed euglycemic diabetic ketoacidosis （euDKA） after taking empagliflozin. METHODS Clinical pharmacists provided pharmaceutical care for a patient with T2DM and LGMD who developed euDKA after taking empagliflozin. According to the patient’s recent use of medications and his conditions， clinical pharmacists assessed the correlation between euDKA and empagliflozin as “very likely”. As to euDKA， clinical pharmacists suggested discontinuing empagliflozin and metformin， and giving intravenous infusion of 10% Glucose injection instead of 5% Glucose injection for fluid resuscitation. Clinical pharmacists monitored the patient’s laboratory indicators such as arterial blood gas analysis， blood/urine ketones and electrolytes. They assisted physicians to decide when to stop intravenous supplements of liquid and insulin. Clinical pharmacists also assisted physicians to adjust the antidiabetic drugs and educated the patient to avoid empagliflozin or other sodium- glucose linked transporter 2 inhibitors （SGLT2i）. RESULTS Physicians adopted the suggestions of clinical pharmacists. After treatment， the patient’s condition improved， and he was allowed to be discharged with medication. CONCLUSIONS euDKA is a relatively rare and serious adverse reaction associated with SGLT2i， and the patients with LGMD are susceptible to euDKA. Clinical pharmacists assist physicians in developing personalized medication plans by evaluating the association between euDKA and empagliflozin， adjusting medication regimens，conducting pharmaceutical monitoring，and other pharmaceutical services. Meanwhile， they provide medication education to patients to ensure their medication safety.

OBJECTIVE To provide a reference for the pharmaceutical care of a patient with type 2 diabetes mellitus （T2DM） and limb-girdle muscular dystrophy （LGMD） who developed euglycemic diabetic ketoacidosis （euDKA） after taking empagliflozin. METHODS Clinical pharmacists provided pharmaceutical care for a patient with T2DM and LGMD who developed euDKA after taking empagliflozin. According to the patient’s recent use of medications and his conditions， clinical pharmacists assessed the correlation between euDKA and empagliflozin as “very likely”. As to euDKA， clinical pharmacists suggested discontinuing empagliflozin and metformin， and giving intravenous infusion of 10% Glucose injection instead of 5% Glucose injection for fluid resuscitation. Clinical pharmacists monitored the patient’s laboratory indicators such as arterial blood gas analysis， blood/urine ketones and electrolytes. They assisted physicians to decide when to stop intravenous supplements of liquid and insulin. Clinical pharmacists also assisted physicians to adjust the antidiabetic drugs and educated the patient to avoid empagliflozin or other sodium- glucose linked transporter 2 inhibitors （SGLT2i）. RESULTS Physicians adopted the suggestions of clinical pharmacists. After treatment， the patient’s condition improved， and he was allowed to be discharged with medication. CONCLUSIONS euDKA is a relatively rare and serious adverse reaction associated with SGLT2i， and the patients with LGMD are susceptible to euDKA. Clinical pharmacists assist physicians in developing personalized medication plans by evaluating the association between euDKA and empagliflozin， adjusting medication regimens，conducting pharmaceutical monitoring，and other pharmaceutical services. Meanwhile， they provide medication education to patients to ensure their medication safety.

Lung cancer is the most common malignant tumor worldwide, ranking first in both incidence and mortality rates. According to the latest statistics from the International Agency for Research on Cancer (IARC), approximately 2.5 million new cases and around 1.8 million deaths from lung cancer occurred in 2022, placing a tremendous burden on global healthcare systems. The high mortality rate of lung cancer is closely linked to its subtle early symptoms, which often lead to diagnosis at advanced stages. This not only complicates treatment but also results in substantial economic losses. Current treatment options for lung cancer include surgery, radiotherapy, chemotherapy, targeted drug therapy, and immunotherapy. Among these, immunotherapy has emerged as the most groundbreaking advancement in recent years, owing to its unique antitumor mechanisms and impressive clinical benefits. Unlike traditional therapies such as radiotherapy and chemotherapy, immunotherapy activates or enhances the patient’s immune system to recognize and eliminate tumor cells. It offers advantages such as more durable therapeutic effects and relatively fewer toxic side effects. The main approaches to lung cancer immunotherapy include immune checkpoint inhibitors, tumor-specific antigen-targeted therapies, adoptive cell therapies, cancer vaccines, and oncolytic virus therapies. Among these, immune checkpoint inhibitors and tumor-specific antigen-targeted therapies have received approval from the U.S. Food and Drug Administration (FDA) for clinical use in lung cancer, significantly improving outcomes for patients with advanced non-small cell lung cancer. Although other immunotherapy strategies are still in clinical trials, they show great potential in improving treatment precision and efficacy. This article systematically reviews the latest research progress in lung cancer immunotherapy, including the development of novel immune checkpoint molecules, optimization of treatment strategies, identification of predictive biomarkers, and findings from recent clinical trials. It also discusses the current challenges in the field and outlines future directions, such as the development of next-generation immunotherapeutic agents, exploration of more effective combination regimens, and the establishment of precise efficacy prediction systems. The aim is to provide a valuable reference for the continued advancement of lung cancer immunotherapy.

ObjectiveTo study the effect and mechanism of Yixintai on mitochondrial fission proteins in the rat model of chronic heart failure. MethodTen of 60 SD rats were randomly selected as the sham operation group， and the remaining 50 rats were subjected to ligation of the left anterior descending coronary artery for the modeling of heart failure post myocardial infarction. The successfully modeled rats were randomized into model， low-， medium-， and high-dose （1.4， 2.8， and 5.6 g·kg^-1， respectively） Yixintai， and trimetazidine （10 mg·kg^-1） groups. The rats were administrated with corresponding doses of drugs by gavage， and the rats in the model group and sham operation group were given an equal volume of normal saline by gavage for 28 consecutive days. Enzyme-linked immunosorbent assay （ELISA） was then employed to measure the levels of amino-terminal pro-B-type natriuretic peptide （NT-pro BNP）， B-type natriuretic peptide （BNP）， and adenosine triphosphate （ATP） in the serum. Color Doppler ultrasound imaging was conducted to examine the cardiac function indicators. Hematoxylin-eosin staining and Masson staining were conducted to observe the pathological changes in the heart， and Image J was used to calculate collagen volume fraction （CVF）. Transmission electron microscopy was employed to observe the ultrastructural changes of myocardial cells. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling （TUNEL） was employed to measure the apoptosis rate of myocardial cells. Western blot was employed to determine the protein levels of mitochondrial fission protein 1 （Fis1） and mitochondrial fission factor （Mff） in the outer mitochondrial membrane of the myocardial tissue. ResultCompared with the sham operation group， the model group showed elevated levels of NT-pro BNP and BNP in the serum， decreased ATP content， left ventricular ejection fraction （LVEF）， and left ventricular fraction shortening （LVFS）， increased left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs）， disarrangement of myocardial cells， inflammatory cell infiltration， increased collagen fibers and CVF， damaged myocardium and mitochondria， and increased apoptosis rate of myocardial cells， and up-regulated expression of Fis1 and Mff in the cardiac tissue （P<0.01）. Compared with the model group， different doses of Yixintai and trimetazidine lowered the serum levels of NT-pro BNP and BNP （P<0.05）， increased the ATP content （P<0.05）， increased LVEF and LVFS （P<0.01）， decreased LVIDd and LVIDs （P<0.01）. Moreover， the drugs alleviated the myocardial inflammatory damage and fibrosis， reduced CVF （P<0.01）， repaired the myocardial mitochondrial structure， and decreased the apoptosis rate of myocardial cells （P<0.01）. Medium- and high-dose Yixintai and trimetazidine down-regulated the expression of Fis1 and Mff in the myocardial tissue （P<0.05）. ConclusionYixintai can improve mitochondrial structure， reduce myocardial cell apoptosis， and improve cardiac function by inhibiting the expression of Fis1 and Mff in the myocardial tissue.

Background Exposures to environmental pollution and specific occupational hazards exacerbate pulmonary fibrosis which has a complex pathogenesis and lacks effective therapeutic drugs. The extract from Dracocephalum moldavica L. can alleviate pulmonary fibrosis through anti-inflammatory and anti-pyroptosis pathways, but its mechanism of prevention and treatment for pulmonary fibrosis remains unclear. Objective To elucidate the targets and potential mechanism underlying the anti-pulmonary fibrosis efficacy of Dracocephalum moldavica L. extract by employing an amalgamation of network pharmacology and empirical verification. Methods The chemical composition of the extract of Dracocephalum moldavica L. was retrieved with the help of China National Knowledge Infrastructure (CNKI) and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The disease targets related to pulmonary fibrosis were inquired using Gene Cards and DisGeNET. A protein-protein interaction (PPI) was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and Cytoscape software. The predicted potential targets were analyzed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses through the Database for Annotation, Visualization and Integrated Discovery (DAVID) and validated by molecular docking. Thirty-two rats were randomly divided into a control group, a model group, a low-dose group of Dracocephalum moldavica L. extract (100 mg·kg⁻¹), and a high-dose group of Dracocephalum moldavica L. extract (400 mg·kg⁻¹), with eight rats in each group. A rat model of pulmonary fibrosis was constructed using bleomycin (5 mg·kg⁻¹) intratracheal instillation, and an equal volume of saline was instilled into the control group. After modelling, 400 and 100 mg·kg⁻¹ of Dracocephalum moldavica L. extract were given the high-dose and low-dose groups by gavage, and an equal volume of saline was given by gavage to the control group and the model group, once per day, for consecutive 28 d. The animals were then neutralized, and lung tissues were collected. Structural changes in rat lung tissue were evaluated by observing stained pathological sections. Western blot (WB) was used to detect fibrosis-related proteins type I collagen (Col-I), α-smooth muscle actin (α-SMA), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) in lung tissues. Real-time fluorescence quantitative PCR (RT-qPCR) was used to detect α-SMA and Col-I mRNA levels in lung tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in rats. Results A total of 378 key chemical components of the Dracocephalum moldavica L. extract and 1611 lung fibrosis-related targets were identified. Among them, 574 potential targets of Dracocephalum moldavica L. extract acting on lung fibrosis were obtained. The key targets determined by Degree value were albumin (ALB), tumour necrosis factor (TNF), AKT1, etc. The results of KEGG analysis suggested that the potential targets of Dracocephalum moldavica L. extract against pulmonary fibrosis mainly involved the PI3K-AKT, HIF-1 signaling pathway, TNF signaling pathway, and MAPK signaling pathway. The molecular docking results showed that the binding energy between the active components (quercetin, apigenin, aesculetin, quercitrin) of Dracocephalum moldavica L. extract and the core targets of pulmonary fibrosis (TNF, IL-6, ALB, AKT1) were all <-29.288 kJ·mol⁻¹, indicating good binding ability. The animal validation results showed that compared with the control group, the rats in the model group had disrupted alveolar structure, obvious inflammatory cell infiltration, positive blue-striped collagen fibre deposition, and increased Col-I and α-SMA protein expression and transcription levels (P<0.001), p-PI3K and p-AKT expression levels (P<0.001), and levels of inflammatory factors TNF-α, IL-6, and IL-1β (P<0.001). Compared with the model group, the high- and low-dose groups of Dracocephalum moldavica L. extract alleviated the progression of pulmonary fibrosis, reduced inflammatory cell infiltration, and attenuated collagen fibre deposition in rats, with a decrease in the protein expression and transcription levels of Col-I and α-SMA (P<0.01), the expression levels of p-PI3K and p-AKT (P<0.001), and the levels of inflammatory factors IL-6 and TNF-α (P<0.05, P<0.001). Conclusion Dracocephalum moldavica L. extract manifests anti-pulmonary fibrotic properties through the modulation of the PI3K-AKT signaling cascade and the suppression of inflammatory reactions.

Microorganisms can form biofilms, complex, heterogeneous, multicellular communities that adhere to surfaces. Biofilm formation on the surface of structures in water will accelerate structures’ corrosion, seriously affect their service efficiency and life, and significantly impact the growth of animals, plants, and human life. Hence, clarifying the mechanism of biofilm formation contributes to developing new strategies to control biofilm formation on surface and then reduce infections, biofouling, and contaminations. Biofilm-targeting strategies include the regulation of established biofilms or the modulation of single-cell attachment. In most studies, physicochemical mechanism is frequently applied to explain the initial bacterial adhesion phenomena but rarely to explain other stages of biofilm formation. This review presents a five-step comprehensive description of the physicochemical process from film formation to biofilm maturation: (1) period of film formation; (2) period of bacterial adhesion; (3) period of extracellular-polymeric-substances (EPSs) membrane formation; (4) period of regulating biofilm by quorum sensing (QS); (5) period of biofilm maturation. We first clarify how the film formed by compound molecules affects the surface’s physicochemical properties and initial adhesion, summarizing many factors that affect bacterial adhesion. We then review the types of EPSs and signal molecules secreted by bacteria after irreversible adhesion, as well as their role and QS mechanism in biofilm maturation. Finally, we discuss how bacteria or microcolonies separate from the mature biofilm by physicochemical action and summarize the morphology and adhesion characterization methods after the biofilm matures. This review redefines the role of physicochemical in the whole process of biofilm formation and provides a theoretical basis for the prevention, removal, and utilization of biofilm and other related research fields.

Objective:To investigate the expression of KCTD8 gene in breast ductal carcinoma and its correlation with clinical factors and prognosis.Methods:Immunohistochemistry technology(IHC)were employed to detect protein expression levels of KCTD8 in 27 pairs of breast ductal carci-noma and its paired adjacent tissues.Analyzing the correlation between changes in KCTD8 expres-sion of protein and clinical factors using statistical techniques.RNA expression and methylation data of breast cancer(including intraductal cancer)were analysed from TCGA database.Result:The pro-tein expression of KCTD8 gene in 27 pairs of breast ductal carcinoma tissues showed a decreasing trend compared to adjacent tissues(P＜0.05),and the decreased expression level of protein was cor-related with the tumor size of patients(P＜0.05).The analysis results of the TCGA database indicate that the expression and hypemethylation of KCTD 8 gene in breast cancer(including intraductal can-cer)tissues affected the prognosis of patients.Conclusion:The reduced protein expression level of KCTD8 gene in breast ductal carcinoma may be involved in the development and affect the prog-nosis of patients.

G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

This paper summarized professor WANG Shouchuan's experience in differentiating and treating children epistaxis from the perspective of "four excess and three deficiency". It is believed that the pathogenesis of children epistaxis is concluded as "four excess and three deficiency"， of which the four excess syndromes are exuberant heat in the lung channel， intense stomach fire， heart fire hyperactivity， and liver fire flaming upward， while the three deficiency syndromes include qi， yin and yang deficiency. Seven methods for treating children epistaxis are summarized. For exuberant heat in the lung channel syndrome， it is recommended to clear lung and direct qi downward， using self-made Xiebai Zhiniu Decoction （泻白止衄汤）. For intense stomach fire syndrome， the method of clearing stomach and draining fire can be used with self-made Qingwei Zhiniu Decoction （清胃止衄汤）. In terms of heart fire hyperactivity syndrome， it is better to clear heart and drain fire， using self-made Daochi Zhiniu Decoction （导赤止衄汤）. For liver fire flaming upward syndrome， it is advised to clear liver and drain fire， using self-made Yimu Zhiniu Decoction （抑木止衄汤）. In terms of qi deficiency syndrome， the method of fortifying spleen and boosting qi and containing blood should be used with self-made Futu Zhiniu Decoction （扶土止衄汤）. If there is yin deficiency syndrome， it is advised to supplement kidney， enrich yin and clear heat， using self-made Zishui Zhiniu Decoction （滋水止衄汤）. If there is yang deficiency syndrome， the method of boosting qi， warming yang and nourishing blood can be used， using self-made Wenpi Zhiniu Decoction （温脾止衄汤）.

GNPS-based mass spectrum-molecular networks is an effective strategy for rapidly identifying known natural products and discovering novel structures. The chemical diversity of azaphilones from the fermentation extracts of Talaromyces sp. HK1-18 was studied by molecular network technique. Three linear tricyclic azaphilones, sequoiamonacins A-C (2a, 2b, 1), were isolated by silica gel column chromatography and high performance liquid chromatography from the extracts of the fungal strain of HK1-18, and their structures were identified by nuclear magnetic resonance and high-resolution mass spectrometry. Guided by the mass spectra of sequoiamonacins A-C (2a, 2b, 1), the cluster of sequoiamonacinoid analogues was discovered from the full molecular networking of HK1-18. By analyzing the MS/MS fragments of each parent ion in this cluster, 7 azaphilones (3-9) included 6 new ones (4-9) were predicted successfully. Then the MS/MS cracking regularity of this type of azaphilones was revealed. Compound 1 showed anti-inflammatory activity, which can inhibit the production of interleukin-1α (IL-1α) in lipopolysaccharide (LPS)-induced mouse macrophage RAW264.7, with an inhibitory rate of 29% at the concentration of 12.5 μg·mL^-1.