BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

[Objective]To summarize Professor CHEN Jian's clinical experience in treating pediatric upper airway cough syndrome,which is based on the"Xuanfu"theory,and to learn how to use wind-dispelling herbs.[Methods]Through clinical observation,medical case organization,literature search and integration of clinical practice experience,this paper elaborates Professor CHEN's understanding of the etiology and pathogenesis of upper airway cough syndrome and summarizes the clinical experience of treating this disease from the perspective of"opening Xuanfu with wind-dispelling herbs",in addition with relevant cases for verification.[Results]Professor CHEN considers the lurking wind in the"Xuanfu"and the upward reversal of lung Qi as the basic pathogenesis when diagnosing and treating pediatric upper airway cough syndrome.The deficiency of Zhengqi and the lack of nourishment in the"Xuanfu"are seen as the root causes of the disease.The obstruction of"Xuanfu"with phlegm,dampness and blood stasis are the pathogenic factors.The prescription is based on"Jiuke"Recipe,with wind-dispelling herbs being a continuous thread throughout.The fundamental treatment approach is using wind-dispelling herbs to treat wind disease,and to open and consolidate the"Xuanfu".The application of wind-dispelling herbs aims to expel wind,open"Xuanfu",overcome dampness and facilitate the flow of"Xuanfu",as well as support and nourish"Xuanfu".The treatment makes differentiation between the nasal and pharyngeal areas,with simultaneous treatment of the lung orifices,ensuring the smooth flow of"Xuanfu"and harmony of the viscera.A case was presented at the end of the paper to illustrate the treatment principle of dispelling wind and opening"Xuanfu",combining both attack and supplementation,leading to the unblocking of"Xuanfu",the expulsion of lurking wind,the transformation of phlegm and dampness and the self-elimination of cough,with a definite therapeutic effect.[Conclusion]Professor CHEN's approach to treating pediatric upper airway cough syndrome with"wind-dispelling herbs to open the Xuanfu"is effective,which provides insights and experience for clinical diagnosis and treatment of the disease,which has significant enlightening significance.

Objective:To observe effect of immunosuppressant cyclophosphamide on"extrapulmonary transmission"of mouse model of influenza virus pneumonia.Methods:BALB/c mice were randomly divided into normal group,virus group,cyclophospha-mide group,virus+cyclophosphamide group.Cyclophosphamide group and virus+cyclophosphamide group were intraperitoneally injected with cyclophosphamide once,24 h afterwards,virus group and virus+cyclophosphamide group were administered nasal influ-enza virus to establish influenza virus infection model,and 3,5,7 days after nasal instillation,lung index,heart index,liver index,spleen index and kidney index were measured by conventional methods;pathological changes of lung tissue,heart tissue,liver tissue,spleen tissue and kidney tissue were observed by HE staining;ELISA was used to detect levels of serum inflammatory cytokines IL-1β,IL-6,TNF-α;RT-qPCR was used to detect influenza virus load and expressions of inflammatory factors IL-1β,IL-6,TNF-α in each tissue.Results:Compared with normal group and virus group,lung index and heart index of mice in virus+cyclophosphamide group were significantly increased(P<0.05 or P<0.01);spleen index was significantly decreased(P<0.05 or P<0.01);lung tissue,heart tissue,liver tissue and spleen tissue showed different degrees of pathological damage;serum inflammatory factor IL-6 level was increased significantly(P<0.05 or P<0.01);lung tissue,heart tissue,liver tissue,spleen tissue and mRNA levels of IAV NP in kidney tissue were significantly increased(P<0.05 or P<0.01);mRNA levels of IL-1β,IL-6 and TNF-α in lung and heart tissues were significantly increased(P<0.05 or P<0.01).Conclusion:Immunosuppressant cyclophosphamide can cause damage to extrapul-monary tissues and organs in a mouse model of influenza virus pneumonia,among which heart damage is the most serious.Cyclophos-phamide is beneficial to establish model of"extrapulmonary transmission"of influenza virus pneumonia.

Cultural confidence is an important part of nurturing"confidence in the path,theory,system,and culture of social-ism with Chinese characteristics"students,as well as the important direction of ideological and political courses,and play an impor-tant role for establishing the core values of Chinese socialism.This paper summarized the reform exploration and practical experience of the Basic Immunology and Pathogen Biology through deeply excavating the core ideas of Chinese medicine culture based on the course content for improving the cultural confidence.The object of this paper is to improving the effectiveness of education.

Objective To study the characteristics of animal models of pulmonary fibrosis so as to provide a reference for the standardization of such models,and to guide research on the pathogenesis,diagnosis,and treatment of pulmonary fibrosis.Methods Studies using experimental pulmonary fibrosis in animals published in the past 10 years were retrieved from the CNKI,Wanfang,VIP,SinoMed,and PubMed databases.Factors including animal species,sex,modeling method,and detection index were summarized,and the data were analyzed using Excel.Results A total of 292 eligible studies were included.The animals mainly included SD rats,Wistar rats,and C57BL/6 mice,and most were male.The most common modeling drugs were bleomycin,paraquat,and silica suspension,mainly administered by intratracheal injection,with a typical modeling cycle of 28 d.The detection indexes mainly comprised lung tissue pathology and measurements of protein expression,cytokine levels,and biochemical indexes.Conclusions SD rats and C57BL/6 mice were the most commonly used animals for experimental pulmonary fibrosis,and intratracheal injection of bleomycin(5 mg/kg)was the most frequently used modeling method.This approach allows for the straightforward and effective replication of pathological features resembling human pulmonary fibrosis,and may serve as a reference for future experimental studies using animal models of pulmonary fibrosis.

Building morality and cultivating people is the fundamental task of national education,and the reform of curricu-lum ideological and political teaching is an important way to realize the task.In the practice of curriculum ideological and political edu-cation,curriculum is the carrier,ideological and political is the direction.In order to explore the ideological and political education mode of professional courses and achieve the educational goal of"casting the soul and educating people",the pathogenic biology teach-ing team of Hunan University of Chinese Medicine takes the basic medical course"Basic Immunology and Pathogenic Biology"as breakthrough point,the team excavated ideological and political elements,built a teaching system,reformed teaching methods,ex-plored and innovated in actual teaching according to course characteristics.Therefore,they achieve certain educational results.This paper summarizes and analyzes the practice and thinking in teaching reform,in order to provide some references for the reform and construction of ideological and political education in colleges and universities.

OBJECTIVE To investigate the use of common disposable and reusable supplies for prevention and con-trol of infections in Shanghai.METHODS A survey was conducted for the use and reuse of disposable high-value consumables,disposable bronchoscopes and environmental cleaning and disinfection tools in Shanghai by using structured questionnaire.RESULTS Totally 81 medical institutions were involved in the survey,44(54.32％)of which were tertiary hospitals,and the median number of beds was 500.The orthopedic implants(70.37％),ul-trasound knife(69.14％)and endoscopic puncture instrument(66.67％)were the high-value consumables rank-ing the top 3 utilization rates.There was reuse of 18 types of high-value consumables in total among the 12 medi-cal institutions.The major causes of reuse of high-value consumables included fee less tan cost of consumables(58.33％)or being unable to included in charge items(33.33％).27.78％of the recycle high-value consumables were not treated with a dedicated disinfection and sterilization system and procedures for the disposable high-value consumables,and 33.33％did not have the report systems for related adverse reactions.49.09％of the medi-cal institutions reported to use the disposable bronchoscopes,4 of which reused them.The majority of the medi-cal institutions could carry out centralized cleaning and disinfection for the recycled floor cloths(60.81％)and cloth towels(56.76％),and 32.43％of the medical institutions reused the cloth towels by manual cleaning.The utilization rate of antiseptic wipes was 75.41％in adult intensive care unit,62.50％in neonatal intensive care unit.CONCLUSION The study reveals that there are some problems in the use of disposal and reusable supplies for prevention and control of infections,which may provide baseline data for management of the related supplies and the surveillance of disinfection of the recycled supplies so as to enhance the quality of management of hospital-asso-ciated infections.

AIM:This study aims to explore the mechanisms of influenza A virus(IAV)-induced macrophage inflammatory injury based on the interleukin-6(IL-6)/signal transducer and activator of transcription 3(STAT3)signaling loop and investigate the intervention effects of Ma-Xing-Shi-Gan decoction(MXSGD)-medicated serum.METHODS:RAW264.7 and BV2 cells were divided into control,Janus kinase(JAK)/STAT signaling pathway activator,inhibitor,model,oseltamivir,antiviral particle,and MXSGD groups.After IAV modeling and serum interventions,the cells were cultured for 24 and 48 h,and the indicators were detected and analyzed.ELISA,RT-qPCR,Western blot,and immuno-fluorescence assay were used to detect the secretion levels of IL-6 in the cell culture supernatant,IL-6 and STAT3 mRNA expressions,protein expression of STAT3,and expression levels of phosphorylated STAT3(p-STAT3),respectively.Pearson correlation analysis was used to evaluate the correlation between p-STAT3 and IL-6 in the two cell types.A co-cul-ture model of the two cells was constructed,and the secretion levels of IL-6 in the cell culture supernatant was measured.Molecular docking analyses were performed for STAT3 and MXSGD.RESULTS:After IAV simulation,the secretion lev-els of IL-6 in the cell culture supernatant,mRNA expression levels of IL-6 and STAT3,and protein expression levels of STAT3 and p-STAT3 in both cell lines were elevated(P<0.05 or P<0.01).Pearson correlation analysis revealed that p-STAT3 expression was positively correlated with IL-6 expression.The secretion levels of IL-6 in the co-culture model in-creased(P<0.01).MXSGD down-regulated the secretion levels of IL-6 in the cell culture supernatant mRNA,expression levels of IL-6 and STAT3,and protein expression levels of STAT3 and p-STAT3 in two kinds of cells(P<0.05 or P<0.01),and inhibited the secretion levels of IL-6 in co-culture models.STAT3 demonstrated good binding energies for liquiritin,amygdalin,and ephedrine.CONCLUSION:IAV can induce inflammatory injury in macrophages,and its mechanism may be related to activation of the IL-6/STAT3 signaling loop.MXSGD may alleviate the pathogenic effects of IAV by modulating the signaling loop.

Objective:Investigate the impact of calcification on the long-term outcomes of patients with coronary chronic total occlusion (CTO) after percutaneous coronary intervention (PCI).Methods:A retrospective cohort study was conducted. Patients who underwent PCI and had at least one CTO lesion at Fuwai Hospital between January 2010 and December 2013 were consecutively enrolled. Calcification was evaluated by coronary angiography, and patients were divided into two groups: moderate/severe calcification group and non/mild calcification group. Clinical follow-up was completed up to 5 years. Incidence of PCI-related complications and immediate procedural outcomes were compared between two groups, and the primary endpoint was the target lesion failure (TLF) at 5 years after PCI. Clinical follow-up endpoint events were analyzed using Kaplan-Meier survival analysis with log-rank test, and Cox multivariate regression model was used to evaluate the relationship between calcification and TLF.Results:The study included 2 659 CTO patients with an age of (57.2±10.5) years, of whom 442 (16.6%) were female, and among whom 13.5% (360/2 659) had moderate/severe calcification. Compared with the non/mild calcification group, the moderate/severe calcification group had a higher incidence of PCI-related complications (43.2% (156/361) vs. 32.5% (772/2 374), P<0.001) and procedural failure (34.3% (124/361) vs. 24.3% (577/2 374), P<0.001). Additionally, the moderate/severe calcification group showed a higher risk of the primary endpoint event (TLF) during the 5-year follow-up (19.8% vs. 15.3%, log-rank P=0.028). Higher incidence of cardiac death was observed in moderate/severe calcification group (5.7% vs. 2.7%, log-rank P=0.003). Cox multivariate regression analysis revealed that moderate/severe calcified plaques remained an independent risk factor for 5-year TLF after CTO-PCI ( HR=1.34, 95% CI: 1.01-1.79, P=0.043). Conclusion:Compared with CTO patients with non/mild calcification, those with moderate/severe calcification have higher procedural failure and complication rates, as well as poorer long-term prognosis, mainly due to an increase in cardiac death.

Objective:To investigate the clinicopathological features, pathological classification, and molecular characteristics of pulmonary hamartomas.Methods:A retrospective analysis was conducted on 316 cases of pulmonary hamartomas diagnosed at Nanjing Chest Hospital, Nanjing, China from January 2015 to June 2024. Next generation sequencing (NGS) was performed on 15 cases of this study. The clinical data, histopathological features, immunophenotypes, and molecular alterations were analyzed. Relevant literature was reviewed.Results:Among the 316 patients, there were 154 males and 162 females, with an average age of 56±10 years. Among the 316 cases, 310 were intrapulmonary hamartomas and 6 were intraluminal bronchial hamartomas. Microscopically, there were complex proliferative mesenchymal components and epithelial components, presenting various combinations and hamartomatous morphologies. These hamartomas were morphologically classified into mesenchymal-type hamartomas (cartilaginous, fibrous, smooth muscle, adipose tissue, and mixed types) and epithelial-mesenchymal mixed-type hamartomas (respiratory epithelial-mesenchymal mixed and mucosal gland-mesenchymal mixed types). The cartilaginous hamartomas accounted for 72.8% (230/316) of them, and the non-cartilaginous hamartoma accounted for 27.2% (86/316). Secondary changes such as calcification, ossification, collagenization, mucin degeneration, and cystic changes were commonly present. The immunophenotype was CK7 +/TTF1 + for respiratory epithelial cells, or TTF1 -/CK7 +/p40 + for interstitial cells. Interstitial cells might express desmin, SMA, S-100, caldesmon, etc, while CD34 +/CD10 +/ER + spindle-shaped interstitial cells were also commonly noted. Genetic variations were detected in 11 of the 15 cases that were subject to NGS, including HMGA2-related fusion genes, EP300 mutations, FLT1 mutations, JAK1 mutations, SETD2 and TAP2 mutations, and high-copy amplification of CDK4/PHF1/TSPAN31. The patients were followed up for 6 to 110 months without any known recurrence or metastasis. Conclusions:Pulmonary hamartomas mainly occur in the peripheral lung parenchyma, with the cartilaginous type being the most common. Their clinical pathological and molecular features of pulmonary hamartomas are characterized and the histological types are roughly ascertained in this study, with emphasis of the key points of diagnosis and differential diagnosis. Classification of pulmonary hamartomas is valuable for guiding future research. Pulmonary hamartomas overall have a good prognosis. However, those with cystic changes or intraluminal hamartomas in the bronchus may cause serious airway lesions and therefore require special attention.