BACKGROUND:Repetitive trans-spinal magnetic stimulation(rTSMS)can inhibit inflammatory responses following spinal cord injury.rTSMS applies magnetic field stimulation to the spinal cord region to modulate neuronal excitability and synaptic transmission,thereby promoting plasticity and repair of the nervous system. OBJECTIVE:To observe the effects of rTSMS on the Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB/NLRP3 signaling pathway after spinal cord injury and explore its mechanism in promoting motor function recovery. METHODS:Male C57BL/6J mice,SPF grade,were randomly divided into sham surgery group,spinal cord injury group,and rTSMS group.The latter two groups of mice were anesthetized and the T9 vertebral plate was removed using rongeur forceps to expose the spinal cord,and the spinal cord was clamped using a small aneurysm clip for 20 seconds to establish the spinal cord injury model.Mice in the rTSMS group underwent a 21-day rTSMS intervention starting on day 1 after spinal cord injury.The stimulation lasted 10 minutes per day,5 days per week with an interval of 2 days.Basso Mouse Scale scores were used to assess motor function recovery in mice after spinal cord injury at 1,3,7,14,and 21 days after spinal cord injury.Western blot was employed to detect the expression of AQP4,apoptotic factors Bax,Bcl-2,CL-Caspase-3,inflammatory factors tumor necrosis factor-α,interferon-γ,interleukin-6,interleukin-4,and the TLR4/NF-κB/NLRP3 signaling pathway related proteins in the injured spinal cord.Oxidative stress assay kit was used to measure the activity of superoxide dismutase,glutathione peroxidase,and malondialdehyde content at the site of spinal cord injury.Immunofluorescence staining was performed to detect the expression of neuronal nuclei(NeuN). RESULTS AND CONCLUSION:The Basso Mouse Scale score in the rTSMS group was significantly higher than that in the spinal cord injury group(P<0.05).Compared with the spinal cord injury group,the rTSMS group showed a reduction in spinal cord water content.The expression of AQP4 protein,malondialdehyde content,and expression of Bax,Bcl-2,CL-Caspase-3,tumor necrosis factor-α,interferon-γ,interleukin-6,and TLR4/NF-κB/NLRP3 signaling pathway related proteins were all decreased in the rTSMS group,while the activities of superoxide dismutase and glutathione peroxidase,as well as the expression of Bcl-2,interleukin-4,and NeuN,were all increased(P<0.05).These results suggest that rTSMS downregulates the expression of proteins related to the TLR4/NF-κB/NLRP3 signaling pathway,alleviating symptoms after spinal cord injury such as spinal cord edema,oxidative stress,apoptosis,and inflammation,exerting neuroprotective effects,and thereby promoting the recovery of hindlimb motor function after spinal cord injury.

Objective:To investigate the predictive value of systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), and CT perfusion imaging (CTP) parameters for early neurological deterioration (END) in patients with mild stroke duo to anterior circulation large vessel occlusion.Methods:Patients with minor stroke duo to anterior circulation large vessel occlusion admitted to the First People's Hospital of Suqian from November 2021 to December 2023 were included. Minor stroke was defined as a baseline National Institutes of Health Stroke Scale (NIHSS) score ≤ 5, and END was defined as an increase of ≥ 4 in NIHSS score within 24 hours of admission compared to the baseline. SIRI and SII were calculated based on the findings of blood routine examination. According to CTP at admission, the cerebral blood volume (CBV) index, infarct core volume, and early infarct growth rate (EIGR) were obtained. Multivariate logistic regression analysis was used to determine the independent risk factors for END. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of each predictor on END. Results:A total of 132 patients were included, with 85 males (64.4%) and a median age of 68 years (interquartile range, 58-77 years). Thirty-nine patients (29.5%) experienced END. The baseline NIHSS score, fasting blood glucose, neutrophil count, lymphocyte count, SIRI, SII, infarct core volume, and EIGR in the END group were significantly higher than those in the non-END group, while the CBV index was significantly lower than that in the non-END group (all P<0.05). Multivariate logistic regression analysis showed that SIRI (odds ratio [ OR] 3.672, 95% confidence interval[ CI] 1.838-6.326; P<0.001), SII ( OR 4.824, 95% CI 2.057-7.135; P<0.001), CBV index ( OR 0.968, 95% CI 0.947-0.986; P<0.001), and EIGR ( OR 2.527, 95% CI 1.918-3.589; P<0.001) were the independent predictive factors of END. ROC curve analysis showed that the area under the curves of SIRI, SII, CBV index, and EIGR for predicting END were 0.780 (95% CI 0.692-0.863), 0.798 (95% CI 0.709-0.888), 0.775 (95% CI 0.697-0.853), and 0.772 (95% CI 0.732-0.829), respectively. Conclusion:SIRI, SII, CBV index, and EIGR are the independent predictive factors of END in patients with minor stroke duo to anterior circulation large vessel occlusion, and have certain predictive value for END.

Aim This study aims to investigate the therapeutic effect and underlying mechanism of Todda-lia asiatica in the treatment of ischemic stroke(IS),utilizing network pharmacology,molecular docking technology,and animal experiments.Methods To screen the chemical components of Toddalia asiatica and its targets related to IS,a database was utilized.A protein-protein interaction(PPI)network was con-structed,followed by KEGG pathway enrichment anal-ysis.Molecular docking was performed to investigate the interaction between the components and target pro-teins.Finally,the effects of the drug on the PI3K/AKT/mTOR pathway and autophagy were validated through animal experiments.We established a middle cerebral artery occlusion(MCAO)rat model and di-vided the rats into the model group,Donepezil hydro-chloride group,Toddalia asiatica group,and sham op-eration group randomly.Observed the pathological changes in neurons of the rat hippocampal and cortical regions induced by the drug,performed immunohisto-chemical analysis to detect and localize mTOR expres-sion,and used Western blot to assess the expression levels of PI3K,p-PI3K,AKT,p-AKT,mTOR,as well as autophagy markers(LC3-Ⅱ and p62).Re-sults A total of 22 active ingredients from Toddalia asiatica,including AKT1 and MAPK3,were identified through screening.Additionally,194 signaling path-ways,such as PI3K/AKT and MAPK,were analyzed.The active compounds in Toddalia asiatica demonstra-ted stable binding affinity with targets associated with ischemic stroke.The results of the animal experiment indicated that,compared to the sham-operated group,the neuronal distribution in the hippocampal and corti-cal regions of the model group rats became sparser and more disorganized.There was a decrease in the number of Nissl bodies and cytoplasmic vacuolization.The ex-pression of mTOR-positive cells in the hippocampal and cortical regions was reduced.Additionally,the ex-pression levels of p-PI3K,p-AKT,mTOR,and p62 in the rat hippocampal tissue decreased(P＜0.05,P＜0.01),while the expression of LC3-Ⅱ increased(P＜0.01).Compared with the model group,the rats in the Toddalia asiatica and the Donepezil hydrochloride groups effectively improved the aforementioned indica-tors in rats.Conclusions Network pharmacology a-nalysis has revealed the promising potential of Toddalia asiatica in treating ischemic stroke,attributed to its di-verse components,targets,and pathways.The animal experiment showed that Toddalia asiatica can protect the neuronal structure in the hippocampal and cortical regions,which may be related to the inhibition of ex-cessive autophagy mediated by the PI3 K/AKT/mTOR pathway.

Aim To investigate the effect of Celastrol on the expression of Ezrin in tissues and HaCaT cells of DNCB sensitisation-induced atopic dermatitis(AD)mice.Methods BALB/c mice were taken and ran-domly divided into the control,DNCB group,Celastrol 25 μg,50 μg,75 μg treatment group,and Dex group,with 8 mice in each group;HaCaT cells were induced with TNF-α and treated with 1 μmol·L-1 Celastrol and Ezrin siRNA.The thickness of the skin on the ear and back of mice was measured by a thickness gauge,and the spleen and lymph nodes of mice were taken to observe the changes.HE and toluidine blue staining were used to observe the inflammatory cells and mast cell infiltration in mice.Flow cytometry was used to detect the levels of IL-4 and TNF-α in the lymph nodes of mice,and enzyme-linked immunosorbent was used to determine the levels of IL-4,TNF-α and IgE in serum of mice,and the expression of IL-4,IL-5 and IL-13 in the supernatant of HaCaT cells.Western blot was used to detect the expression of P-Ezrin and Ezrin in skin tissues.Results Celastrol significantly inhibited the swelling of ear and back skin tissues,reduced the de-granulation of inflammatory cells and mast cells,low-ered serum IgE and serum and lymph node levels of IL-4 and TNF-α,and reduced the activation of Ezrin in mice,and the expression of IL-4,IL-5 and IL-13 in the supernatant of HaCaT cells was restored by the treat-ment with Ezrin siRNA.Conclusion Celastrol amel-iorates AD,which may be achieved by modulating Ezrin activation.

The standard system refers to the scientific organic whole formed by the internal connections of stand-ards within a certain range.The completeness of the drug standard system plays a crucial role in ensuring drug safety.Pharmacopoeia is the core of the drug standard system.This article compared the architecture of the Chi-nese Pharmacopoeia,the United States Pharmacopoeia,the European Pharmacopoeia,and the Japanese Pharma-copoeia on the aspects of overall architecture,monographs architecture,general notice architecture,general tech-nical requirements architecture,and other standard architecture,as well as the implementation of various types of standards,aiming to provide reference for the optimization and improvement of the standard system of the Chinese Pharmacopoeia.

Fulminant myocarditis occurs suddenly and progresses rapidly, often leading to severe heart failure, hypotension, or cardiogenic shock. Widespread myocardial calcification secondary to fulminant myocarditis is clinically rare, with sporadic reports both domestically and internationally. This article reports a case of a young female patient who presented with acute onset and rapidly deteriorating condition, with imaging indicating myocardial calcification by the second day of hospitalization, highlighting the unusual speed of progression.

We designed and synthesized eighteen lycorine derivatives with five different structural types, and evaluated their antiviral activities on a HCoV-OC43-infected H460 cell model. Structure-activity relationships suggested that the introduction of appropriate substituents on the 6N atom of lycorine was beneficial to activity. Compound 6a gave a good activity with the half effective concentration (EC₅₀) and selectivity index (SI) values of 2.36 μmol·L^-1 and 16.52, respectively. Surface plasmon resonance (SPR) result indicated that 6a might target the non-structural protein 12 (NSP12) subunit in RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 with the dissociation constant (K_D) value of 1.36 μmol·L^-1. Molecular docking indicated that 6a might act on nidovirus RdRp-associated nucleotidyltransferase (NiRAN) catalytic center of NSP12, distinct from the mechanism of nucleoside-like drugs such as remdesivir. This study provides scientific data for the development of lycorine derivatives into a new class of anti-SARS-CoV-2 small molecule inhibitors.

In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC₅₀ values of 3.77 μmol·L^-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.

Objective To investigate the expression level and clinical significance of microRNA(miR)-181c and microRNA(miR)-578 in the serum of patients with sepsis complicated by acute kidney injury(AKI).Methods Eighty patients with sepsis complicated by AKI(AKI group)and 80 patients with simple sepsis(non AKI group)who were hospitalized in Sinopharm Gezhouba Central Hospital from January 2022 to December 2022 were collected as research subjects.The serum levels of miR-181c and miR-578 in two groups were detected and compared.Logistic regression was applied to analyze the influencing factors of sepsis patients complicated by AKI.Receiver operating characteristic(ROC)curve was applied to analyze the predictive value of serum miR-181c and miR-578 levels for patients with sepsis complicated by AKI.Results The proportion of pulmonary infection,the level of arterial blood lactic acid,creatinine,urea nitrogen and APACHEⅡ score in AKI group were higher than those in non-AKI group,and the oxygenation index was lower,the differences were statistically significant(χ2=7.364,t=14.298,26.691,17.925,7.104,12.676,all P＜0.05).The serum miR-181c level in the AKI group(1.47±0.36)was higher than that in the non AKI group(1.03±0.28),the serum miR-578 level(0.76±0.19)was lower than that in the non AKI group(1.05±0.31),and the differences were statistically significant(t=8.629,7.134,all P=0.000).Logistic regression analysis showed that miR-181c[OR(95%CI):2.984(1.628～5.468)],pulmonary infection[OR(95%CI):1.946(1.250～3.031)],arterial blood lactic acid[OR(95%CI):1.457(1.073～1.978)],and APACHE Ⅱ score[OR(95%CI):2.283(1.393～3.741)]were risk factors for AKI in sepsis patients(all P＜0.05);miR-578[OR(95%CI):0.742(0.631～0.873)]and oxygenation index[OR(95%CI):0.342(0.130～0.904)]were protective factors(all P＜0.05).The combined prediction of serum miR-181c and miR-578 for AKI in sepsis patients had an AUC of 0.915,a sensitivity and a specificity of 83.65%,88.75%,respectively,which was superior to their individual predictions(Z=3.118,3.460,P=0.002,0.001).Conclusion The serum miR-181c expression is obviously up-regulated and miR-578 expression is obviously down-regulated in patients with sepsis complicated by AKI.The combination of the two has good reference value for predicting sepsis complicated by AKI.

Objective To provide reference for the optimization and improvement of interoperability between the standard system of the Chinese Pharmacopoeia and other standards.Methods The interoperability of various pharmacopoeia standard systems was compared by searching for citations from the Chinese Pharmacopoeia,the United States Pharmacopoeia-National Formulary,the European Pharmacopoeia,the Japanese Pharmacopoeia,and other standards,including references to domestic regulations and guidelines,standards of the International Organization for Standardization,guidelines from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use,documents of the World Health Organization,and standards from other countries and international organizations.Results In recent years,pharmacopoeias in the world had continuously increased the citation of non pharmacopoeial standards.The types,quantities,and fields of the United States Pharmacopoeia-National Formulary referencing other standards far exceed those of other pharmacopoeias.The Chinese Pharmacopoeia cites the least number of other standards.Conclusion It is suggested that the Chinese Pharmacopoeia should enhance the interoperability with other standard systems in the standards of various professional fields,enhance the openness,harmonization and advantages,and form a more complete standard system.