This paper aimed to investigate the therapeutic effect and mechanism of action of the Yiqi Fumai Formula(YQFM), a kind of traditional Chinese medicine(TCM), on mice with experimental heart failure based on the "heart-gut axis" theory. Based on the network pharmacology integrated with the group collaboration algorithm, the active ingredients were screened, a "component-target-disease" network was constructed, and the potential pathways regulated by the formula were predicted and analyzed. Next, the model of experimental heart failure was established by intraperitoneal injection of adriamycin at a single high dose(15 mg·kg~(-1)) in BALB/c mice. After intraperitoneal injection of YQFM(lyophilized) at 7.90, 15.80, and 31.55 mg·d~(-1) for 7 d, the protective effects of the formula on cardiac function were evaluated using indicators such as ultrasonic electrocardiography and myocardial injury markers. Combined with inflammatory factors in the cardiac and colorectal tissue, as well as targeted assays, the relevant indicators of potential pathways were verified. Meanwhile, 16S rDNA sequencing was performed on mouse fecal samples using the Illumina platform to detect changes in gut flora and analyze differential metabolic pathways. The results show that the administration of injectable YQFM(lyophilized) for 7 d significantly increased the left ventricular end-systolic internal diameter, fractional shortening, and ejection fraction of cardiac tissue of mice with experimental heart failure(P<0.05). Moreover, markers of myocardial injury were significantly decreased(P<0.05), indicating improved cardiac function, along with significantly suppressed inflammatory responses in cardiac and intestinal tissue(P<0.05). Additionally, the species of causative organisms was decreased, and the homeostasis of gut flora was improved, involving a modulatory effect on PI3K-Akt signaling pathway-related inflammation in cardiac and colorectal tissue. In conclusion, YQFM can affect the "heart-gut axis" immunity through the homeostasis of the gut flora, thereby exerting a therapeutic effect on heart failure. This finding provides a reference for the combination of TCM and western medicine to prevent and treat heart failure based on the "heart-gut axis" theory.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Heart Failure/microbiology* ; Mice ; Mice, Inbred BALB C ; Male ; Disease Models, Animal ; Gastrointestinal Microbiome/drug effects* ; Heart/physiopathology* ; Humans ; Signal Transduction/drug effects*

Aim To investigate the potential role and related mechanisms of protein phosphatase 2Cm(PP2Cm)overexpression in atorvastatin-induced insu-lin resistance.Methods Male C57BL/6J mice,fibro-blast growth factor 21 knockout(FGF21-KO)mice,and wildtype(WT)mice were raised for 12 weeks to construct models.Groups included atorvastatin,con-trol,atorvastatin+PP2Cm overexpression(OE),FGF21-KO+vehicle,FGF21-KO+PP2Cm OE,WT+vehicle,WT+PP2Cm OE.Body weight,fasting blood glucose levels,fasting insulin levels,and intraperitoneal glucose tolerance tests(IPGTT)were measured in 4,8 and 12 weeks.The concentrations of branched-chain a-mino acids(BCAA)in cells,tissues and serum,as well as the mRNA and protein expression of BCAA cat-abolic enzymes,were determined by qRT-PCR,Western blot and ELISA after atorvastatin treatment.Further-more,the effects of PP2Cm overexpression on these in-dicators were explored,and the FGF21 was verified in vivo and in vitro.Results Atorvastatin induced insu-lin resistance in mice,altered insulin,glucose tolerance and increased BCAA levels.PP2Cm overexpression mitigated these changes.In the Atorvastatin+PP2Cm OE group,FGF21 mRNA,protein and concentration were all significantly upregulated.Regardless of PP2Cm overexpression,the knockout of FGF21 signifi-cantly increased BCAA expression levels,both fasting insulin and blood glucose levels were significantly high-er than those in WT group.Conclusions FGF21 may be an important regulator of PP2Cm involved in atorv-astatin-induced insulin resistance.PP2Cm overexpres-sion alleviates the effects of atorvastatin-induced insulin resistance by regulating FGF21.

19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

AIM: To analyze the clinical outcomes of cyclosporine combined with lacrimal plug in the treatment of dry eye in patients with primary Sjögren's syndrome.METHODS: The clinical data of 60 patients(120 eyes)who were admitted to the ophthalmology department and rheumatology and immunology department of Baoding No.1 Central Hospital and were diagonosed with siogren's syndrome dry eye after multidisciplinary consultation from June 2022 to September 2023 were retrospectively analyzed. All the patients received regular treatment of primary Sjögren's syndrome, and they were divided into three groups according to treatment methods: A, B and C, with 20 cases(40 eyes)in each group. The group A received 0.3% sodium hyaluronate eyedrops, the group B received 0.3% sodium hyaluronate eyedrops plus 0.05% cyclosporine eyedrops, and the group C received 0.3% sodium hyaluronate eyedrops plus 0.05% cyclosporine eyedrops combined with binocular lacrimal plugs. The ocular surface disease index(OSDI)score, conjunctival hyperemia score, tear film breakup time(BUT), tear meniscus height(TMH), corneal fluorescein staining(FL)score and tear secretion of the three groups of patients were compared before and at 4, 8 and 12 wk after treatment. The contents of inflammatory factors such as interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in tears were detected before and at 12 wk after treatment.RESULTS: At 4, 8 and 12 wk after treatment, the scores of OSDI, conjunctival hyperemia score and FL in the three groups of patients were lower than those before treatment, and the BUT, TMH and tear secretion were higher than those before treatment(all P<0.001). The OSDI score of the group C was lower than that of the group A and B, and the group B was lower than the group A(all P<0.001). The BUT, TMH and tear secretion of the group C were higher than those of the group A and B, with the group B higher than the group A(all P<0.001). At 12 wk after treatment, the levels of IL-6, TNF-α and IL-1β in the tears of the three groups of patients were lower than those before treatment, with the group C lower than the group A and B, and the group B lower than the group A(all P<0.001). There was no statistical significant difference in the incidence of adverse reactions among the three groups of patients(P>0.05).CONCLUSION: The combined use of cyclosporine and lacrimal plug is safe and effective in improving the clinical symptoms of patients with moderate and severe dry eye, promoting the function of tear film and cornea, increasing tears secretion, and reducing the level of tear inflammatory factors.

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

Objective To investigate the effect and mechanism of hypoxia inducible factor-1 α/aquaporin-4(HIF-1α/AQP4)pathway in high altitude cerebral edema(HACE)after blood-brain barrier injury in rats.Methods Adult male SD rats(n=40)were randomly divided into two groups:control group(Ctrl,n=20)and high altitude cerebral edema group(HACE,n=20).The rats in the control group were reared in Xining(altitude 2261 m)for 4 days,and the rats in HACE group were reared in low-pressure simulation chamber(altitude 5000 m)for 4 days.Brain water content was measured by the method of dry and wet weight.The intracranial structure,morphology and signal changes of small animals were observed through T2 weighted image of 7.0 T MRI.The morphological changes of neurons and the apoptosis of nerve cells in the CA1 region of hippocampal tissue were observed by the staining of Nissl and TUNEL.Immunohistochemical staining was performed to observe the extravasation of immunoglobulin G(IgG).The expressions of HIF-1α,AQP4,matrix metalloproteinase-9(MMP-9),claudin-5,occludin and zonula occludens-1(ZO-1)in the tissue of hippocampal were detected by the method of Western blotting and immunofluorescent staining.Results The brain water content increased significantly in the HACE group(P＜0.05).The neurons in CA1 region of hippocampal tissue were atrophic and deformed,the arrangement of neurons was disordered in the HACE group.The number of neurons decreased significantly,the apoptosis of nerve cells increased significantly,and the IgG exudates obviously in the CA1 region of hippocampal tissue in the HACE group.The expressions of HIF-1α,AQP4 and MMP-9 proteins increased significantly,while claudin-5,occludin and ZO-1 proteins decreased significantly in the CA1 region of hippocampal tissue,which detected by the method of Western blotting and immunofluorescent staining(P＜0.05).Conclusion Acute high-altitude hypoxia can induce to blood-brain barrier disruption through the HIF-1α/AQP4 pathway,resulting in high-altitude cerebral edema.

Objective:To investigate the efficacy and safety of the combination therapy of venetoclax (VEN) and azacitidine (AZA) in treatment of newly diagnosed elderly patients with acute myeloid leukemia (AML).Methods:A retrospective cohort study was conducted. The clinical data of 17 newly diagnosed elderly AML patients who received VEN+AZA regimen at the First Hospital of Putian City from April 2021 to June 2023 were collected. Treatment outcomes and adverse events were analyzed. Survival curves were plotted by using the Kaplan-Meier method, and intergroup comparisons were performed by using the log-rank test.Results:Among the 17 patients, the median age [ M ( Q1, Q3)] was 70 (68, 74) years, with 11 males (64.7%) and 6 females (35.3%). The median number of treatment courses was 4.0 (2.5, 8.5). After the first course, the composite complete remission (cCR) rate was 41.2% (7/17), minimal residual disease (MRD) negativity rate was 5.9% (1/17), and overall response rate (ORR) was 82.4% (14/17). By the end of follow-up in September 2023, the cCR rate reached 64.7% (11/17), MRD negativity rate was 52.9% (9/17), and ORR was 88.2% (15/17). The median number of courses to achieve cCR was 1.0 (1.0, 2.0), and to achieve MRD negativity was 3.0 (2.0, 3.5). The follow-up rate was 88.2% (15/17), and the median follow-up time was 17.3 months (95% CI: 7.0-27.6 months). The median progression-free survival (PFS) time was 6.5 months (95% CI: 1.7-11.3 months), and median overall survival (OS) time was 12.0 months (95% CI: 0.3-23.7 months). The median OS time after progression was 1.5 months (95% CI: 1.0-2.0 months). All patients experienced hematological adverse events, with 94.1% (16/17) experiencing grade ≥ 3 hematological adverse events. The most common non-hematological adverse event was infection (88.2%, 15/17), with the lung being the most frequent site of infection (82.4%, 14/17), while 41.2% (7/17) of patients had pre-existing infections before treatment. Conclusions:The VEN+AZA regimen demonstrates high remission rates and significant efficacies in treating newly diagnosed elderly AML patients. Although adverse events occur in nearly all patients, most are able to tolerate the treatment.

Plastic pharmaceutical packaging materials are widely used in drug packaging,and the effective quality control of these materials is of great significance for ensuring the quality of drugs.The Guidelines for Plastic Materials and Containers for Pharmaceutical Packaging in the 2025 Edition of the Pharmacopoeia of the People's Republic of China(hereinafter referred to as the guideline)is based on the characteristics of plastic pharmaceutical packaging materials and combined with the different uses of various products,clarifying the quality control requirements for different categories of products.The guideline not only improves the pharmacopoeia standard system,but also meets the needs of industrial development and drug regulation under the new situation,which is conducive to enterprises to better improve product quality.This article explains the main contents of the guideline in combination with the background,process,and ideas of its drafting,so as to provide guidance for the correct understanding and use of this standard by all parties in the industry.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.