Based on the theory of evidence-based medicine （EBM）， this paper systematically constructed a multi-dimensional evaluation framework for traditional Chinese medicine （TCM） appropriate technologies， encompassing three core dimensions including evidence， practitioner， and patient. For the current practical challenges in the promotion of TCM technologies such as lack of high-quality evidence， inconsistent operational standards， and varying patient acceptance， the paper proposed the integration of published literature evidence and real-world research data to construct a scientific and applicable evaluation pathway. Regarding the evidence dimension， it emphasizes syste-matic assessment of effectiveness， safety， and economic efficiency， introducing methods like the target trial emulation framework to enhance evidence quality； for the practitioner dimension， it suggests developing multi-aspects competency evaluation tools based on educational background， training assessment， and clinical outcomes； for the patient dimension， it recommends designing patient acceptance assessment tools by considering factors such as technical characte-ristics， expected efficacy， patient-practitioner interaction， and the availability of alternative treatments. The purpose of the above measures is to provide methodological support for the standardized popularization and precision application of TCM appropriate technologies.

This study investigated the effects and underlying mechanisms of the luteolin-naringenin combination(LN)on liver injury induced by acetaminophen(APAP).Forty-eight Kunming mice were randomly allocated into six groups:a normal control group,an APAP-induced liver injury model group,a positive drug treatment group,and three LN treatment groups with low,medium,and high doses.After the final drug administration,the mice were fasted for 12 hours prior to eu-thanasia for sample collection.Serum transaminase activity,oxidative stress indices,and hematoxy-lin-eosin(HE)staining were assessed to evaluate the effects of LN on APAP-induced hepatic inju-ry.Additionally,Western blot analysis was conducted to examine the expression levels of sphingo-sine kinase 1(SPHK1)and endoplasmic reticulum stress(ERS)-related proteins,thereby elucida-ting the potential mechanisms by which LN mitigates APAP-induced liver injury.The results dem-onstrated that varying concentrations of LN effectively ameliorated serum aminotransferase activi-ty and oxidative stress levels induced by APAP in a dose-dependent manner.Histopathological ex-amination via HE staining revealed significant improvement in APAP-induced liver tissue injury following treatment with different concentrations of LN.Furthermore,Western blot analysis indi-cated that the protein expressions of SPHK1,CHOP,p-IRE1α,ATF6,p-PERK,p-eIF2α,and ATF4 were markedly reduced after administration of various concentrations of LN.The results demonstrate that LN exhibits a significant protective effect against APAP-induced liver injury by inhibiting the SPHK1-mediated aberrant expression of ERS-related molecules.This study high-lights the importance of targeting SPHK1 in the treatment of APAP liver injury and provides a no-vel therapeutic approach through the multi-target and multi-pathway combination of monomers.

Multimorbidity has become a widely recognized public health problem worldwide. Identifying multimorbidity patterns can improve not only the efficiency of healthcare resource utilization but also patients' prognosis. This article summarizes three common approaches for the identification of multimorbidity patterns: association analysis methods (including association rule mining and network analysis), classification methods (including cluster analysis, latent class analysis, and latent transition analysis), and dimensionality reduction and feature extraction methods (including principal component analysis, factor analysis, and multiple correspondence analysis), introduces the application of these methods using data from the UK Biobank to identify multimorbidity patterns and discusses and compares the results of case analysis to provide reference for the selection of appropriate methods for multimorbidity pattern research.

This study investigated the effects and underlying mechanisms of the luteolin-naringenin combination(LN)on liver injury induced by acetaminophen(APAP).Forty-eight Kunming mice were randomly allocated into six groups:a normal control group,an APAP-induced liver injury model group,a positive drug treatment group,and three LN treatment groups with low,medium,and high doses.After the final drug administration,the mice were fasted for 12 hours prior to eu-thanasia for sample collection.Serum transaminase activity,oxidative stress indices,and hematoxy-lin-eosin(HE)staining were assessed to evaluate the effects of LN on APAP-induced hepatic inju-ry.Additionally,Western blot analysis was conducted to examine the expression levels of sphingo-sine kinase 1(SPHK1)and endoplasmic reticulum stress(ERS)-related proteins,thereby elucida-ting the potential mechanisms by which LN mitigates APAP-induced liver injury.The results dem-onstrated that varying concentrations of LN effectively ameliorated serum aminotransferase activi-ty and oxidative stress levels induced by APAP in a dose-dependent manner.Histopathological ex-amination via HE staining revealed significant improvement in APAP-induced liver tissue injury following treatment with different concentrations of LN.Furthermore,Western blot analysis indi-cated that the protein expressions of SPHK1,CHOP,p-IRE1α,ATF6,p-PERK,p-eIF2α,and ATF4 were markedly reduced after administration of various concentrations of LN.The results demonstrate that LN exhibits a significant protective effect against APAP-induced liver injury by inhibiting the SPHK1-mediated aberrant expression of ERS-related molecules.This study high-lights the importance of targeting SPHK1 in the treatment of APAP liver injury and provides a no-vel therapeutic approach through the multi-target and multi-pathway combination of monomers.

A 36-year-old male presented to the Department of Neurosurgery of the Second People′s Hospital of Hunan Province on February 12, 2024, due to "10 days of aggravated paroxysmal headache and 1 day of mental abnormality". Ten days ago, after catching a cold, the patient developed persistent low fever and paroxysmal headache. On February 12, 2024, acuted mental and behavioral abnormalities developed, including slow response, self-talk, defecation and urination, no sense of shame and other mental and behavioral abnormalities. On February 22nd, metagenomic next-generation sequencing (mNGS) in cerebrospinal fluid confirmed feline rickettsia infection. One week after doxycycline anti-rickettsia treatment, cerebrospinal fluid mNGS results indicated that the etiology turned negative, and the clinical symptoms improved. Mental disorders caused by rickettsial encephalitis in cats are rare but clinically significant. This case highlights the diagnostic value of mNGS in critical and difficult cases, and supports its integration with traditional diagnostic techniques to achieve precision medicine.

Objective To construct a logistic regression prediction model for stress ulcer(SU)after cerebral hemorrhage.Methods A total of 230 patients with cerebral hemorrhage admitted to our hospital from January 2020 to January 2023 were prospectively selected as the study subjects.They were randomly di-vided into a training group and a validation group using a random number table method,with 115 patients in each group.The incidence of postoperative SU was statistically compared between the two groups.The least absolute shrinkage and selection operator(Lasso)and logistic regression were used to analyze the influencing factors of SU after cerebral hemorrhage,and a logistic regression prediction model was established and valida-ted.Results The incidence of SU was 19.13%in the training group and 20.00%in the validation group.In-crement of age,blood loss≥30 mL,higher levels of neutrophil-to-lymphocyte ratio(NLR),heat shock protein 70(HSP70)and HSP90 were identified as independent risk factors for SU after cerebral hemorrhage(P<0.05),while lower levels of Glasgow Coma Scale(GCS)score and albumin(Alb)were protective factors(P<0.05).The prediction model was logit(P)=0.409×age+1.288×blood loss-1.335×GCS score-1.126×Alb+0.452×NLR+1.483×HSP70+1.593×HSP90-10.325.The areas under the receiver operat-ing characteristic(ROC)curve(AUC)for the training group and the validation group were 0.845(95%CI:0.765-0.906)and 0.855(95%CI:0.777-0.913),respectively.The sensitivities were 81.82%and 90.91%,and the specificities were 76.34%and 70.97%,respectively.Conclusion A logistic regression prediction model was successfully constructed,which has certain predictive value for SU after cerebral hemorrhage.

Objective To observe the changes of myelin sheath in corpus callosum on non-ischemic side after ischemic stroke in rats with cerebral ischemia/reperfusion(I/R)model,and to investigate the effect of vagus nerve stimulation(VNS)on secondary demyelination in I/R model.Methods Forty-two rats were randomly assigned to sham,I/R,or I/R+VNS groups,with 14 rats in each group.Except for the sham group,the rats in other groups were used to construct I/R model by a middle cerebral artery occlusion thread method.In addition,the rats in the I/R+VNS group were given repetitive electrical stimulation of the left vagus nerve for 60 min at 30 min after ischemia occlusion.The cerebral infarction volume was observed by 2,3,5-triphenyltetrazolium chloride staining.The expression levels of myelin basic protein(MBP)and myelin-associated glycoprotein(MAG)in the corpus callosum on the non-ischemic side were detected by Western blotting.The integrity and thickness of myelin sheaths in the corpus callosum on the non-ischemic side were observed by Luxol fast blue staining and transmission electron microscopy,respectively.Results Compared with the sham group,the volume of cerebral infarction in the I/R group was increased(P＜0.01).On the 3rd day after I/R,compared with the sham group,the expression levels of MBP and MAG were significantly decreased(both P＜0.01),the intensity of Luxol fast blue staining was significantly decreased(P＜0.01),and the thickness of the myelin sheath was significantly thinner(g-ratio was increased,P＜0.01)in the corpus callosum on the non-ischemic side.Compared with the I/R group,the expression levels of MBP and MAG in the I/R+VNS group were significantly increased(both P＜0.05),the intensity of Luxol fast blue staining was significantly increased(P＜0.01),and the thickness of myelin sheath was significantly increased(g-ratio was decreased,P＜0.01)in the corpus callosum on the non-ischemic side.Conclusion Secondary demyelination occurs on the non-ischemic side of the rat corpus callosum after ischemic stroke,and VNS can ameliorate the demyelination.

Objective:To investigate the clinicopathological characteristics of lung transplantation and post-transplantation changes in patients with pneumoconiosis.Methods:A retrospective study was conducted to analyze the clinical and pathological data of 28 patients with pulmonary silicosis who underwent lung transplantation and were managed at the Department of Internal Medicine, Henan Provincial People′s Hospital, Zhengzhou, China from January 2015 to December 2024. Among them, 8 patients underwent lung biopsy 6-20 months after transplantation to evaluate the histopathological changes of the recipient and the donor lungs post-transplantation. The expression of relevant indicators was examined using immunohistochemical EnVision staining, while presence of microorganisms was assessed using histochemical special staining. The patients were all followed up.Results:Among the 28 patients with pneumoconiosis who underwent lung transplantation, 26 were male and 2 were female, with a male-to-female ratio of 13∶1. Their ages ranged from 23 to 68 years, median 50.0 (46.0, 53.5) years. They were diagnosed with pneumoconiosis at local occupational disease prevention and control centers for 3 to 15 years (mean, 9.65 years), including 13 left single lung transplants and 15 right single lung transplants. Gross examination showed fleshy nodules with irregular cystic cavities at the periphery. The cut surfaces exhibited gray-brown color and firm texture. Microscopically, most alveolar structures of the lung were obliterated, with nodular or diffuse proliferation of collagen fibers accompanied by hyaline degeneration. Focal massive carbon dust deposition and massive silicotic fibrosis were observed, surrounded by lung parenchyma with emphysematous changes and localized bullae formation. Seven patients underwent re-biopsy after transplantation that showed extensive infiltration of inflammatory cells. In 4 cases, microscopy revealed complete coagulative necrosis, with negative acid-fast staining and TB-DNA results. Of the 4 cases, 3 cases exhibited Aspergillus infection confirmed by Grocott′s methenamine silver and PAS stains, while 2 cases showed chronic bronchitis with squamous metaplasia. Follow-up revealed that 8 patients died of acute respiratory failure due to severe infection, while the remaining 20 demonstrated significant postoperative improvement in lung function.Conclusions:For patients with advanced pulmonary dust deposition disease who undergo lung transplantation, it is necessary to conduct standardized sampling and pathological assessment of the recipient lungs. In the early post-transplant period, the complications of re-biopsy tissues are mainly fungal infections. The combination of morphological manifestations and immunohistochemical detection is helpful to distinguish infection from rejection reactions. At the same time, it is essential to integrate clinical information and laboratory results to provide post-transplantation pathological assessment for individualized treatment.

Porcine epidemic diarrhea virus (PEDV) is an intestinal coronavirus that can cause porcine epidemic diarrhea, leading to diarrhea, vomiting, weight loss, and even death in piglets. Due to the diversity of PEDV strains, traditional vaccines are difficult to sustainably and effectively prevent and control PEDV. This article reviews the strategies and mechanisms of active substances in regulating intracellular signaling pathways, viral proteins, and microbial metabolites to enhance the host immune function against PEDV. It emphasizes the prevention of PEDV resistance and the potential harm of PEDV breaking through interspecies barriers to the human society, aiming to provide reliable theoretical support for the development of new antiviral drugs or vaccines.
Porcine epidemic diarrhea virus/immunology* ; Animals ; Swine ; Swine Diseases/prevention & control* ; Antiviral Agents/pharmacology* ; Coronavirus Infections/virology* ; Viral Vaccines/immunology* ; Humans ; Signal Transduction

ObjectiveTo investigate the effect and molecular mechanism of exosomes derived from bone marrow mesenchymal stem cells（BMSC-exos） modified with Bushen Yisui capsule（BSYS）-containing serum on promoting the differentiation and maturation of OLN-93 oligodendrocytes by regulating miR-15b/Wnt signaling pathway. MethodsOLN-93 cells were divided into 5 groups， including the normal（NC） group， BMSC-exos group， BSYS-BMSC-exos group， BSYS-BMSC+LV-miR-15b-5p inhibitor-exos group， and BSYS-BMSC+LV-miR-15b-5p NC-exos group. DiR staining was used to observe the uptake of Exos by OLN-93 cells. The effective dosage of BSYS-BMSC-exos on OLN-93 cells was assessed by cell proliferation and activity assay（CCK-8）. Stable BMSCs lentiviral transfection strains were established to inhibit miR-15b-5p expression in both BMSCs and their exos， and transfection efficiency was verified by real-time fluorescent quantitative polymerase chain reaction（Real-time PCR） detection of miR-15b-5p. The expressions of 2′，3′-cyclic nucleotide 3′-phosphodiesterase（CNPase） and myelin proteolipid protein（PLP） in OLN-93 cells were detected by immunocytochemistry（ICC） and Western blot. The mRNA expressions of miR-15b-5p and Wnt3a in OLN-93 cells were detected by Real-time PCR， and the protein expression of Wnt3a was measured by Western blot. The expression levels of key molecules in the Wnt/β-catenin signaling pathway of OLN-93 cells， including glycogen synthase kinase（GSK）-3β， β-catenin， and T-cell specific transcription factor 4/transcription factor 7-like 2（TCF4/TCF7L2）， were measured by Real-time PCR and Western blot. ResultsDiR-labeled Exos were efficiently taken up by OLN-93 cells. The CCK-8 assay results indicated that 20 mg·L^-1 of BSYS-BMSC-exos exhibited the most significant effect in enhancing OLN-93 cell viability（P<0.01） and this dosage was selected for subsequent experiments. Following lentiviral transfection of BMSCs， Real-time PCR results revealed that miR-15b-5p was significantly suppressed in BMSCs（P<0.01）， and miR-15b-5p was also notably inhibited in BSYS-BMSC-exos（P<0.01）. ICC analysis further revealed an increase in the number of differentiated， mature CNPase and PLP-positive cells following BSYS-BMSC-exos treatment（P<0.01）. Western blot results demonstrated that the protein expression of CNPase and PLP was significantly enhanced with BSYS-BMSC-exos treatment（P<0.01）. Additionally， BSYS-BMSC-exos also increased the expression levels of miR-15b-5p and p-β-catenin proteins in OLN-93 cells， while decreased the mRNA and protein expressions of Wnt3a， as well as the mRNA expressions of β-catenin and TCF4/TCF7L2， and the protein expression level of p-GSK-3β（Ser9） was significantly reduced（P<0.05， P<0.01）. After the transfection of miR-15b-5p inhibitor into BSYS-BMSC-exos， the above effects were significantly diminished（P<0.05， P<0.01）. ConclusionBSYS-BMSC-exos facilitate the differentiation and maturation of OLN-93 cells， and its mechanism is related to the upregulation of miR-15b-5p in OLN-93 cells， which inhibits the expression of Wnt3a and thereby suppresses the Wnt signaling pathway.