Shegan Mahuangtang was a famous classical formula for treating asthma and is included in the the Catalogue of Ancient Famous Classical Formulas（The Second Batch）. By means of bibliometrics， this study conducts a textual research and analysis on the key information of its formula origin， composition， drug origins， processing， dosage， decocting methods， efficacy， and clinical application. According to research， Shegan Mahuangtang was first recorded in Synopsis of the Golden Chamber and is the ancestral formula for treating cold asthma， which has been used to this day. Suggestions for the drug origins in Shegan Mahuangtang is as follows：Shegan is selected from the dried rhizomes of Belamcanda chinensis（Iridaceae）， Mahuang is selected from the dried herbaceous stems of Ephedra sinica（Ephedraceae）， Shengjiang is selected from the fresh rhizomes of Zingiber officinale（Zingiberaceae）， Xixin is selected from the dried roots and rhizomes of Asarum heterotropoides var. mandshuricum， A. sieboldii var. seoulense or A. sieboldii（Aristolochiaceae）， Ziwan is selected from the dried roots and rhizomes of Aster tataricus（Compositae）， Kuandonghua is selected from the dried flower buds of Tussilago farfara（Compositae）， Nanwuweizi is selected from the dried mature fruits of Schisandra sphenanthera（Magnoliaceae）， Dazao is selected from the dried mature fruit of Ziziphus jujuba（Rhamnaceae）， and Banxia， a plant of the Araceae family， is selected as the processed products of dried tubers from Pinellia ternata. The recommended dosage is 41.4 g of Shegan， Xixin， Ziwan and Kuandonghua， 55.2 g of Mahuang and Shengjiang， 37.5 g of Nanwuweizi， 21 g of Dazao， 34.5 g of Banxia. The decoction method is to boil Mahuang first in 2.4 L of water， remove the froth on the top， and add the rest of the herbs and decoct them together， and then boil them to 600 mL， and then take it at warm temperature， 200 mL each time， 3 times a day. In terms of clinical application， Shegan Mahuangtang is most commonly used for respiratory system diseases， especially in the treatment of adult or pediatric bronchial asthma and cough variant asthma. Phlegm sound in the throat is the core symptom of Shegan Mahuangtang in clinical practice， and the core pathogenesis is "cold fluid stagnated in the lungs". By excavating and sorting out the ancient and modern literature of Shegan Mahuangtang， key information is confirmed， which can provide literature reference for the modern clinical application and new drug development of this famous classical formula.

Severe pneumonia is one of the most common and critical respiratory diseases in clinical practice. It is characterized by rapid progression， difficult treatment， high mortality， and many complications， posing a significant threat to the life and health of patients. The pathogenesis of severe pneumonia is highly complex， and studies have shown that its occurrence and development are closely related to multiple signaling pathways. Currently， the treatment of severe pneumonia mainly focuses on anti-infection， mechanical ventilation， and glucocorticoids， but clinical outcomes are often not ideal. Therefore， finding safe and effective alternative therapies is particularly important. In recent years， with the deepening of research into traditional Chinese medicine （TCM）， it has gained widespread attention in the treatment of severe pneumonia. This paper reviewed the relationship between severe pneumonia and relevant signaling pathways in recent years and how TCM regulated these pathways in the treatment of severe pneumonia. It was found that TCM could regulate the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB）， Janus kinase （JAK）/signal transducer and activator of transcription （STAT）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， NOD-like receptor protein 3 （NLRP3）， and nuclear factor E₂-related factor 2 （Nrf2） signaling pathways， playing a role in reducing the inflammatory response， inhibiting cell apoptosis and pyroptosis， improving oxidative stress， and other effects in the treatment of severe pneumonia. Among these pathways， it was found that all of them regulated inflammation to treat severe pneumonia. Therefore， reducing inflammation is the core mechanism by which Chinese medicine treats severe pneumonia. This review provides direction for the clinical treatment of severe pneumonia and offers a scientific basis for the research and development of new drugs.

Xanthine oxidase (XO) is an important therapeutic target for the treatment of hyperuricemia and gout. Based on the previously identified potent XO inhibitor 1, seventeen oxadiazoles and their ring-opening analogues were designed and synthesized via the bioisostere replacement strategy. Among them, compounds 2l, 2n, and 3b showed obvious XO inhibitory activity at the concentration of 10 μmol·L^-1, and compound 3b exhibited an IC₅₀ value of 1.45 μmol·L^-1.

OBJECTIVE To summarize the current situation of pharmaceutical clinic service in our hospital over the past five years， and explore sustainable development strategies for service models of pharmaceutical clinics. METHODS A retrospective analysis was conducted on the consultation records of patients who registered and established files at the pharmaceutical clinic in our hospital from January 2019 to December 2023. Statistical analysis was performed on patients’ general information， medication- related problems， and types of pharmaceutical services provided by pharmacists. RESULTS A total of 963 consultation records were included， among which females aged 20-39 years accounted for the highest proportion （66.04%）； obstetrics and gynecology- related consultations accounted for the largest number of cases. Additionally， 80 patients attended follow-up visits at our hospital’s pharmaceutical clinic. A total of 1 029 medication-related issues were resolved， including 538 cases of drug consultations （52.28%）， 453 medication recommendations （44.02%）， 22 medication restructuring（2.14%）， and 16 medication education （1.55%）； the most common types of medication-related problems identified were adverse drug events（70.07%）. CONCLUSIONS Although the pharmaceutical clinic has achieved recognition from clinicians and patients， challenges such as low awareness among healthcare providers and the public persist. Future efforts should focus on strengthening information technology construction， enhancing pharmacist training， and establishing various forms of outpatient pharmaceutical service models.

Cells and exosomes derived from them are extensively used as biological carrier systems. Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins, while exosomes, due to their small size, cross barriers and penetrate tumors efficiently. However, challenges remain, cells' large size restricts tissue penetration, and exosomes have limited targeting accuracy and short circulation times. To address these challenges, we developed a novel concept termed exosomal spheres. This approach involved incorporating platelet-derived exosomes shielded with phosphatidylserine (PS) and linked via pH-sensitive bonds for drug delivery applications. The study demonstrated that, compared with exosomes, the exosomal spheres improved blood circulation through the upregulation of CD47 expression and shielding of phosphatidylserine, thereby minimizing immune clearance. Moreover, the increased expression of P-selectin promoted adhesion to circulating tumor cells, thereby enhancing targeting efficiency. Upon reaching the tumor site, the hydrazone bonds of exosome spheres were protonated in the acidic tumor microenvironment, leading to disintegration into uniform-sized exosomes capable of deeper tumor penetration compared to platelets. These findings suggested that exosome spheres addressed the challenges and offered significant potential for efficient and precise drug delivery.

Approximately 20% to 30% of the global workforce is engaged in shift work. As a significant cause of circadian disruption, shift work is closely associated with an increased risk for periodontitis. Nevertheless, how shift work-related circadian disruption functions in periodontitis remains unknown. Herein, we employed a simulated shift work model constructed by controlling the environmental light-dark cycles and revealed that shift work-related circadian disruption exacerbated the progression of experimental periodontitis. RNA sequencing and in vitro experiments indicated that downregulation of the core circadian protein brain and muscle ARNT-like protein 1 (BMAL1) and activation of the Gasdermin D (GSDMD)-mediated pyroptosis were involved in the pathogenesis of that. Mechanically, BMAL1 regulated GSDMD-mediated pyroptosis by suppressing NOD-like receptor protein 3 (NLRP3) inflammasome signaling through modulating nuclear receptor subfamily 1 group D member 1 (NR1D1), and inhibiting Gsdmd transcription via directly binding to the E-box elements in its promoter. GSDMD-mediated pyroptosis accelerated periodontitis progression, whereas downregulated BMAL1 under circadian disruption further aggravated periodontal destruction by increasing GSDMD activity. And restoring the level of BMAL1 by circadian recovery and SR8278 injection alleviated simulated shift work-exacerbated periodontitis via lessening GSDMD-mediated pyroptosis. These findings provide new evidence and potential interventional targets for circadian disruption-accelerated periodontitis.
Pyroptosis/physiology* ; ARNTL Transcription Factors/metabolism* ; Animals ; Periodontitis/etiology* ; Mice ; Phosphate-Binding Proteins/metabolism* ; Shift Work Schedule/adverse effects* ; Intracellular Signaling Peptides and Proteins/metabolism* ; Mice, Inbred C57BL ; Male ; Disease Models, Animal ; Gasdermins

OBJECTIVE: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently develop central nervous system damage, yet the mechanisms driving this pathology remain unclear. This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant (lineage B.1.351). METHODS: K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant. Viral replication, pathological phenotypes, and brain transcriptomes were analyzed. Gene Ontology (GO) analysis was performed to identify altered pathways. Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot. RESULTS: Pathological alterations were observed in the lungs of both mouse strains. However, only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection, accompanied by neuropathological injury and weight loss. GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses, including type I interferons, pro-inflammatory cytokines, Toll-like receptor signaling components, and interferon-stimulated genes. Neuroinflammation was evident, alongside activation of apoptotic and pyroptotic pathways. Furthermore, altered neural cell marker expression suggested viral-induced neuroglial activation, resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks. CONCLUSION These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
Animals ; COVID-19/genetics* ; Mice ; Brain/metabolism* ; Apoptosis ; Mice, Inbred C57BL ; SARS-CoV-2/physiology* ; Pyroptosis ; Gene Expression Profiling ; Transcriptome ; Male ; Female

Maxing Shigan Decoction is first mentioned in Shang Han Za Bing Lun. The original formula consists of Ephedrae Herba, Armeniacae Semen Amarum, Glycyrrhizae Radix et Rhizoma, and Gypsum Fibrosum, and is a clinical prescription for treating cough and asthma. This article analyzed and verified the prescription source, composition, indications, dosage, processing method, decoction and administration method of Maxing Shigan Decoction. This study collected a total of 171 ancient books related to Maxing Shigan Decoction, among which 41 books recorded its key information in detail, covering 57 valid entries. In terms of medicinal ingredients, it is recommended to use Ephedra sinica Stapf, a plant in the Ephedrae Herba family, to dry the herbaceous stem of Ephedra sinica without the need for node removal; Glycyrrhiza uralensis Fisch. et Rhizoma is processed using dried roots and rhizomes of the legume plant Glycyrrhiza uralensis, and processed by honey roasting; Armeniacae Semen Amarum is made from dried and mature seeds of Prunus armeniaca L., a plant in the Rosaceae family, which are crushed when used; Gypsum Fibrosum is selected from sulfate mineral gypsum group gypsum. Suggested dosage: 55.2 g Ephedrae Herba, 111 g Gypsum Fibrosum, 27.6 g Glycyrrhizae Radix et Rhizoma, and 20 g Armeniacae Semen Amarum. The decoction method is to use 1 400 ml of water; first, fry the ephedra to 1 000 ml, remove the foam, add the remaining medicine, decoct 400 ml, remove the sediment, and warm orally taken 200 ml twice a day. Maxing Shigan Decoction has the functions of resolving superficies syndrome with pungent and cool natured drugs, clearing lung-heat and relieving asthma. Its main indications are diverse, involving multiple disciplines such as typhoid fever, warm diseases, pediatrics, and ophthalmology. However, its pathogenesis is generally attributed to the presence of "external wind pathogen and pathogenic heat congesting lung". By analyzing the ancient and modern literature on Maxing Shigan Decoction, the key information of its composition and dosage, drug origin and processing, decoction and administration methods, and functional indications is confirmed, in order to provide a basis for the clinical application and new drug development of Maxing Shigan Decoction.

Objective To investigate the expression and clinical significance of serum C-C motif chemokine ligand 11(CCL11)and phosphorylated neurofilament heavy chain(pNF-H)in diabetic peripheral neuropathy(DPN).Methods A total of 174 patients with type 2 diabetes mellitus(T2DM)were enrolled as T2DM group,and 87 healthy volunteers who underwent physical examina-tions during the same period were selected as control group.The T2DM patients were divided into DPN group and non-DPN group based on the occurrence of DPN.According to the disease severity[assessed by the Toronto Clinical Scoring System(TCSS)],DPN patients were further classified into mild DPN group,moderate DPN group and severe DPN group.Enzyme-linked immunosorbent assay was used to measure the levels of CCL11 and pNF-H.Pearson correlation analysis was employed to examine the correlations of serum CCL11 and pNF-H levels with TCSS scores in DPN patients.Multivariate uncon-ditional logistic regression analysis was conducted to screen for influencing factors of DPN in T2DM pa-tients.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive value of serum CCL11 and pNF-H levels for the development of DPN in T2DM patients.Results The serum levels of CCL11 and pNF-H in the T2DM group were significantly higher than those in the control group(P＜0.05).The incidence of DPN in the T2DM group was 47.13％(82/174).The age of the DPN group was significantly older,the disease course was significantly longer,and the levels of fasting blood glucose,HbA1c,CCL11 and pNF-H were significantly higher than those of the non-DPN group(P＜0.05).The serum levels of CCL11 and pNF-H increased sequentially from the mild DPN group to the moderate DPN group and then to the severe DPN group,with statistically sig-nificant differences(P＜0.05).Serum CCL11 and pNF-H levels in DPN patients were positively correlated with TCSS scores(r=0.661 and 0.619;P＜0.001).A prolonged disease duration,high glycated hemoglobin levels,high CCL11 levels and high pNF-H levels were independent risk factors for DPN in T2DM patients(P＜0.05).Thearea under the ROC curve for the combined pre-diction of DPN in T2DM patients by serum CCL11 and pNF-H levels was 0.861,which was greater than those for the individual indicators by serum CCL11(0.751)and pNF-H(0.765)levels(P＜0.05).After 1,000-time bootstrap internal validation through self-sampling,the C-index for the combined prediction was 0.861.Conclusion Elevated serum levels of CCL11 and pNF-H are in-dependently associated with the development of DPN in T2DM patients and increase with the worse-ning of DPN.The combination of these two markers has a high predictive value for DPN in T2DM patients.