ObjectiveTo investigate the differences in the regulatory effects of formulas containing Ephedrae Herba and Armeniacae Semen Amarum （Mahuangtang， Sanaotang， and Maxing Shigantang） on thermosensitive transient receptor potential ion channels （thermo TRPs） in the mouse model of asthmatic airway inflammation. MethodsSixty female C57BL/6 mice were allocated into blank， model， dexamethasone （0.75 mg·kg^-1）， Mahuangtang （3.8 g·kg^-1）， Sanaotang （2.8 g·kg^-1）， and Maxing Shigantang （6.6 g·kg^-1） groups （n=10）. The mouse model of asthma was established with ovalbumin （OVA） and treated with normal saline （blank group） or corresponding drugs （10 mL·kg^-1）， once a day， 19-28 days after modeling. The levels of eosinophils （EOS） in peripheral blood and white blood cell （WBC） in bronchoalveolar lavage fluid （BALF）， changes in enhanced pause （Penh）， and pathological damage of lung tissue were observed in each group. Western blot and real-time PCR were employed to quantify the protein and mRNA levels， respectively， of high-temperature thermosensitive channels （TRPV1 and TRPV3） and low-temperature thermosensitive channels （TRPA1 and TRPM8） in the lung tissue. ResultsCompared with the blank group， the model group showed a typical asthma phenotype， including elevations in the level of EOS in peripheral blood， level of WBC in BALF， and value of Penh （P<0.05，P<0.01）， and severe lung tissue damage. Compared with the model group， the three formulas alleviated the asthma phenotype to varying degrees （P<0.05，P<0.01）. Compared with the blank group， the model group showed up-regulated protein levels of TRPV1 and TRPA1 in the lung tissue （P<0.01）. Compared with the model group， Maxing Shigantang and Sanaotang groups showed down-regulated protein levels of TRPV1 and TRPA1 （P<0.05， P<0.01）. Moreover， Maxing Shigantang and Sanaotang groups showed more significant down-regulation in protein levels of TRPV1 and TRPA1， respectively （P<0.01）， while no obvious regulatory effect was observed in the Mahuangtang group. Compared with those in the blank group， the protein levels of TRPV3 and TRPM8 were up-regulated in the model group （P<0.01）. Compared with the model group， Maxing Shigantang and Sanaotang down-regulated the protein levels of TRPV3 and TRPM8 （P<0.01）. Moreover， Maxing Shigantang and Sanaotang exerted stronger down-regulating effects on TRPV3 （P<0.05） and TRPM8 （P<0.01）， respectively. Compared with the blank group， the model group presented up-regulated mRNA levels of TRPV1， TRPV3， TRPA1， and TRPM8 in the lung tissue （P<0.01）， and such up-regulations were significantly decreased by Maxing Shigantang and Sanaotang （P<0.01）. Moreover， Maxing Shigantang outperformed Sanaotang in regulating high-temperature thermosensitive channels TRPV1 and TRPV3 （P<0.05， P<0.01）. The regulation effect of the， Maxing Shigantang on high-temperature thermosensory channel proteins of TRPV1 and TRPV3 was better than that of the Sanaotang P<0.05P<0.01while the Sanaotang outperformedhad a significant regulatory effect on Maxing Shigantang in regulating the low-temperature thermosensory thermosensitive channel proteins of TRPA1 and TRPM8which was better than that of the Maxing Shigantang （P<0.05，P<0.01）. ConclusionThe experimental results showed that Mahuangtang， Sanaotang， and Maxing Shigantang all had protective effects on asthma airway inflammation.while Mahuangtang did not show the regulatory effect on TRPV1 and or TRPA1. Maxing Shigantang preferred to regulate high-temperature thermosensory thermosensitive channels of TRPV1 and TRPV3 channels， and Sanaotang preferred to regulate low-temperature thermosensory thermosensitive channels of TRPA1 and TRPM8.

Objective: To investigate the association between brain and muscle Arnt like protein 1( BMAL 1) gene and ambulatory blood pressure (ABP) parameters in college students, and to explore the influence of the interaction between the gene and weight status on the ABP levels, so as to provide reference for early prevention of chronic cardiovascular diseases related to hypertension. Methods: During September 2022 to June 2024, a total of 510 college students were recruited from a university in Changsha, China for on site questionnaire investigation, physical examination, ABP monitoring and genotyping testing. Multiple linear regression method was used to explore the association between the BMAL 1 gene and ABP indicators. An interaction term was included in the general linear model of multiple linear regression to analyze the interactive effects of BMAL 1 gene polymorphisms and weight status on ABP levels. Results: The prevalence of abnormal 24 hour blood pressure, abnormal daytime blood pressure, and abnormal nighttime blood pressure were 3.3%, 3.1%, and 3.9%, respectively. Multiple linear regression analysis showed that the BMAL 1/rs7950226 polymorphism was positively correlated with the 24 hour diastolic blood pressure(DBP) and the daytime DBP level after adjusting for gender, age, and body mass index( β =0.87,0.99, both P <0.05). Also, interaction between BMAL 1/ rs 11022775 and weight status on the nighttime DBP level ( P interaction =0.03) was found. The CC genotype carriers had significantly higher nighttime DBP level ( β =3.52, P <0.05) among overweight/obesity college students, but no differences in nocturnal DBP levels were observed between CC genotype carriers and TT+CT genotype carriers among college students with normal body weight( P > 0.05). Conclusions The rs 7950226 polymorphism is associated with 24 hours DBP and daytime DBP levels. Significant interaction between rs 11022775 with weight status on the nighttime DBP level is found among college students.

The American College of Radiology recently published the appropriateness criteria for initial imaging assessment of chronic pancreatitis （CP） and acute inflammation superimposed on CP （ACP）. These criteria systematically elaborate on the role of various imaging modalities in diagnosing CP and ACP， assessing disease severity， identifying underlying causes， and evaluating complications， in order to provide guidance for effective management of CP patients through early and accurate imaging techniques and with reference to clinical and laboratory assessments. This article gives an excerpt of the key statements from the criteria.

Based on ancient and modern literature， this paper systematically elucidates the concept， physiological characteristics， and reproductive significance of tiangui （天癸）， and further reviews its theoretical connotation throughout the entire process of male reproductive function， covering its onset， maturation， maintenance， disorder， and decline. In terms of its physiological foundation， tiangui is rooted in kidney essence and regulates male reproductive function through the coordination of zang-fu （脏腑） organs. It possesses characteristics of being time-limited， rhythmic， relatively independent， targeted， and functionally diverse. The occurrence of male reproductive diseases is closely related to the abnormality of tiangui， which primarily manifests as tiangui deficiency and dysregulation of tiangui timing. In clinical practice， treatment should follow the principle of "supplementing its deficiency and regulating its timing"， so as to restore the operating rhythm of tiangui.

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Objective To analyze the clinical efficacy of real-world bulleyaconitine A tablets combined with salt and pepper seven-seed hot package in the treatment of knee osteoarthritis(KOA).Methods 110 outpatient patients from the Department of Orthopedics,Shenzhen Traditional Chinese Medicine Hospital from December 2023 to August 2024 were selected,they were randomly divided into control group of 53 cases and treatment group of 57 cases.The patients in control group were treated with flurbiprofen gel paste,the patients in treatment group received oral administration of bulleyaconitine A tablets and external application of Jiaoyan Qizi hot package,the treatment course were all 4 weeks.All patients were followed up for 2 weeks after the end of treatment.Western Ontario and McMaster University osteoarthritis index(WOMAC)score,Lequesne score,12-item short form health survey(SF-12)score and clinical efficacy were compared between two groups,and adverse events were recorded.Results The total effective rate of treatment group was 87.7％,which was significantly higher than 71.7％of control group(P＜0.05);After treatment,WOMAC score,Lequesne score and SF-12 score in two groups were better than before treatment(P＜0.05).The improvement of WOMAC score,Lequesne score and SF-12 score in treatment group were more obvious(P＜0.05).Conclusion For KOA patients with cold and damp obstruction syndrome,the use of bulleyaconitine A tablets combined with Jiaoyan Qizi hot package can alleviate knee joint pain,improve knee joint mobility,and enhance patients'quality of life.

Objective To investigate the mechanism by which Huangqi Guizhi Wuwu decoction(HQGZWWD)regulates nerve injury(NI)through vascular endothelial growth factor(VEGF)pathway based on a combination of network pharmacology and molecular docking techniques.Methods Active ingredients and targets of HQGZWWD were identified through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.A drug-ingredient-target network was constructed by integrated with data from OMIM,GeneCards,and CTD databases to identify VEGF/NI-related targets.Protein-protein interaction analyses were conducted by using STRING network platform,which were further analyzed by using the DAVID database for Gene Ontology/Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment.A"compound-target-pathway"network was constructed by using Cytoscape.Molecular docking was performed to validate the binding ability of core components with the targets.Results The primary constituents(quercetin,kaempferol)and principal targets[signal transducer and activator of transcription 3(STAT3),caspase 3,epidermal growth factor receptor(EGFR),etc.]of HQGZWWD were identified.KEGG analysis revealed that the targets were enriched cancer,EGFR inhibitor resistance,and advanced glycation end-products-receptor for advanced glycation end-products etc.signaling pathways.Molecular docking demonstrated binding energy between core components and STAT3,caspace 3,EGFR,etc.,specifically,the core components exhibited strong binding energy such as STAT3(≤-7.37kcal/mol).Conclusion HQGZWWD shows potency in suppressing inflammation,oxidative stress,and apoptosis,while promoting neural repair through VEGF regulation.The integration of network pharmacology and molecular docking offers a foundational framework for mechanistic investigations.

Heart failure(HF)is a clinical syndrome that poses a significant threat to patient lives.Renin-angiotensin-aldosterone system inhibitors(RAASi)represent a cornerstone therapy for heart failure with reduced ejection fraction, enhancing patient prognosis.Hyperkalemia is a prevalent complication of HF and a common adverse effect associated with the use of RAASi, often resulting in the withdrawal or dose reduction of these medications in certain heart failure patients during clinical practice.A debate exists regarding whether hyperkalemia itself, or the insufficient dosing of RAASi due to hyperkalemia, contributes to poor outcomes in HF patients.This article reviews recent domestic and international research on HF associated with hyperkalemia and discusses the effects of hyperkalemia and RAASi treatment patterns on the clinical outcomes of HF patients, while exploring strategies for managing hyperkalemia in this population.

Objective:To investigate the use of non-vitamin K antagonist oral anticoagulants(NOACs)and their associated comorbidities in patients aged 80 years and older with non-valvular atrial fibrillation(NVAF), as well as to understand the challenges faced by elderly patients receiving NOAC therapy.Methods:We retrospectively enrolled elderly patients(≥80 years old)with NVAF who were treated with NOACs at a hospital in Beijing from January 2018 to August 2023.Patients were categorized into two age groups: 80-89 years and ≥90 years.We collected baseline data, including demographic characteristics, details of atrial fibrillation, comorbidities, laboratory test results, and medication combinations, for descriptive statistical analysis and intergroup comparisons.Results:A total of 695 elderly patients with NVAF receiving NOACs were included in the study, with a median age of 84 years.Among these patients, there were 328 males(47.19%, 328/695)and 422 cases of paroxysmal atrial fibrillation(60.72%, 422/695).The age group of 80-89 years comprised 640 cases(92.09%, 640/695), while the group aged 90 years and above included 55 cases(7.91%, 55/695).The use of NOACs in patients aged 90 and older exhibited an increasing trend over the years.Inter-group comparisons indicated that the ≥90 years group had lower body mass index, longer hospital stays, increased bedridden time, poorer renal function, lower levels of albumin and hemoglobin, and higher D-dimer levels.Inappropriate dosing of DOACs occurred in 49.64%(345/695)of cases, with 90.72%(313/345)receiving doses lower than recommended.Lower-than-recommended doses were more prevalent in the ≥90 years group, while higher-than-recommended doses were more common in the 80-89 years group.Polypharmacy was noted in 61.29%(426/695)of patients.The concurrent use of antiplatelet drugs, rhythm control medications, and ventricular rate control drugs was observed in 12.52%(87/695), 19.57%(136/695), and 54.53%(379/695)of patients, respectively, with no significant differences between groups.Conclusions:Inappropriate dosing and polypharmacy are prevalent issues among elderly NVAF patients.Therefore, it is essential to enhance multidisciplinary collaboration to optimize anticoagulation treatment strategies.

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which plays a significant role in contributing to vascular cognitive impairment. While 13-docosenamide is a type of fatty acid amide, it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion. In this study, we conducted bilateral common carotid artery stenosis (BCAS) surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment. Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice. Mechanistically, 13-docosenamide specifically binds to cannabinoid receptor 1 (CNR1) in oligodendrocyte precursor cells (OPCs). This interaction results in an upregulation of ubiquitin-specific peptidase 33 (USP33)-mediated CNR1 deubiquitination, subsequently increasing CNR1 protein expression, activating the phosphorylation of the AKT/mTOR pathway, and promoting the differentiation of OPCs. In conclusion, our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.
Animals ; Oligodendrocyte Precursor Cells/metabolism* ; Mice ; Cell Differentiation/drug effects* ; Male ; Receptor, Cannabinoid, CB1/metabolism* ; Mice, Inbred C57BL ; Ubiquitin Thiolesterase/metabolism* ; Ubiquitination/drug effects* ; Carotid Stenosis/complications* ; Cognitive Dysfunction/drug therapy*