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 explore the feasibility and safety of submucosal tunneling endoscopic resection(STER)for the treatment of giant(long diameter≥3.5 cm)symptomatic submucosal tumors(SMT)originating from the esophageal and cardiac muscularis propria layer.Methods A retrospective analysis was conducted on patients with giant symptomatic SMT of the esophagus and cardia treated with STER at the Endoscopy Center of Zhongshan Hospital,Fudan University from January 2017 to January 2020.Clinical characteristics and follow-up data of patients were collected.The efficacy of STER was evaluated by complete resection rate,recurrence rate,and residual rate.The safety of the procedure was assessed by the occurrence of procedure-related complications.Results A total of 111 patients with SMT were included,including 65 males and 46 females,with an average age of(43.2±11.6)years old.Among them,11 patients(9.9％)presented with typical symptoms.Leiomyomas accounted for 105 cases,gastrointestinal stromal tumors for 2 cases,and schwannoma for 4 cases.The median long diameter of the tumors was 5 cm,and the median short diameter was 3 cm.The median operation time was 70 minutes,and the median time of hospital stay was 3 days.The success rate of STER was 100％,with a complete resection rate of 73.9％.Intraoperative mucosal injury was observed in 18 cases(16.2％),postoperative complications occurred in 16 cases(14.4％),including severe pneumothorax/pleural effusion requiring drainage in 10 cases(9.0％),delayed bleeding in 1 case(0.9％),moderate or severe fever in 4 cases(3.6％),and infection in tunnel in 1 case(0.9％).Follow-up at 1-18 months showed no tumor residue,recurrence,esophageal stenosis,diverticula or other long-term complications.Conclusions STER is a safe and effective treatment for giant symptomatic SMT of the esophagus and cardia.

AIM:To elucidate the possible biological mechanism of silica-induced acute lung injury in rats.METHODS:Sixteen Male Sprague-Dawley rats were divided into control and acute silicosis model groups,and instilled intratracheally with 1 mL of normal saline and 50 g/L silica suspension,respectively.After 7 d,the rats were sacrificed for collection of lung tissue and serum.The serum levels of interleukin-1β(IL-1β),IL-18 and tumor necrosis factor-α(TNF-α)were measured by using ELISA.The protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)and gasdermin D(GSDMD)were measured by immunohistochemistry.Bacterial DNA was ex-tracted from the lung tissue for 16S ribosomal RNA gene sequencing to characterize changes in the composition of lung flo-ra.The differences in the structure of bacterial flora between control and model groups were analyzed by bioinformatic analy-ses.RESULTS:Immunohistochemical analysis showed that the protein expression levels of NLRP3 and GSDMD were higher in the lungs of the rats in model group.In addition,serum cytokine profiling showed that IL-1β,IL-18 and TNF-α levels were significantly higher in model group.The most abundant bacterial genera in the lung flora of the rats in model group were Bifidobacterium,Clostridium sensu stricto 1,and Parasutterella.The NLRP3 and GSDMD levels in the lung tissue and IL-1β and TNF-α levels in serum were positively correlated with the abundance of Parasutterella.CONCLU-SION:The alterations in lung flora structure and increased inflammation levels may be the actual biological mechanisms underlying silica-induced acute lung injury.The modulation of lung flora may provide a basis for the prevention and treat-ment of silica-induced acute lung injury.

With the increasing application of immune checkpoint inhibitors(ICI)in anti-tumor therapy,ICI related infections are often neglected.Mycobacterium tuberculosis(MTB)is also a common pathogen.We reported a case of ICI related pulmonary tuberculosis from Zhongshan Hospital,Fudan University.Meanwhile,18 cases of ICI related tuberculosis infection were collected through literature search,and the characteristics of ICI related tuberculosis were analyzed to improve the understanding in clinic practice.All the cases were confirmed TB including 15 cases of pulmonary tuberculosis(1 case with complication of intestinal tuberculosis)and 4 cases of extra-pulmonary tuberculosis(1 case of disseminated tuberculosis,bone tuberculosis,tuberculous pericarditis and tuberculous pleurisy,respectively).The chest CT characteristics of pulmonary tuberculosis mainly included centrilobular nodules,ground glass nodules,empty lesions,patchy shadows,consolidation and large infiltration.Eighteen cases started anti-tuberculosis treatment,while 4 cases continued ICI treatment.Three cases suspended ICI(2 cases had remission after reuse)and 11 cases stopped ICI,and 1 case was not mentioned.ICI related tuberculosis may be a direct complication of tumor immunotherapy.It is necessary to screen tuberculosis infection and exclude active tuberculosis before immunotherapy.If there are suspected symptoms such as fever,cough and sputum during ICI treatment,active tuberculosis should be taken into account.

Objective:To observe the effects of electroacupuncture(EA)on sleep electroencephalogram(EEG)and event-related potential(ERP)in patients with somatoform disorders(SFD). Methods:Seventy-five SFD patients were recruited as an EA group to receive EA at Shenting(GV24)and Baihui(GV20)once daily,30 min each time,with 6 straight days as a treatment course,and 4 courses were conducted at 1-day intervals.Before treatment,patients underwent a survey using a physical symptom checklist on their primary symptoms.Before and after treatment,their sleep EEG was monitored using Quisi,and the ERP mismatch negativity(MMN)and P300 were detected.The Quisi sleep EEG and ERP were also examined among 40 normal volunteers as the normal group data. Results:During the trial,13 cases were removed from the EA group due to incomplete data,and 62 cases were finally included for statistical analyses.Of the 62 SFD patients,the main disturbing symptoms were cognitive impairments,sleep disorders,respiratory symptoms,digestive symptoms,five-sense organ problems,and cardiovascular symptoms in order.Before treatment,the EA group had increased MMN and P300 latencies and decreased amplitudes compared with the normal control group(P<0.01 or P<0.05);according to Quisi,the EA group also had reduced total sleep time(TST),shorter rapid eye movement sleep(REM)latency(RL)and REM time(RT),smaller number of REM period(NRP),extended sleep latency(SL),longer awaking time(AT),lower sleep efficiency(SE),larger percent of non-rapid eye movement sleep(NREM)stage 1(S1)and smaller percent of NREM stage 2(S2),and the percent of slow wave sleep(SWS),i.e.NREM stage 3(S3)plus stage 4(S4),also went down,all presenting significant differences between groups(P<0.01 or P<0.05).After 4 courses of treatment,the MMN and P300 latencies were reduced,and their amplitudes became larger in the EA group compared with the baseline(P<0.05);they had insignificant differences compared with the normal control group(P>0.05).Quisi showed that the TST and RL increased,and the SL and AT decreased in the EA group,and the predominant change in sleep architecture was reduced S1 percent,increased S2,and improved SE,all showing significant intra-group differences(P<0.01 or P<0.05);however,the intra-group difference in the NRP was statistically insignificant(P>0.05).Except the TST,RT,S1 percent,and SWS,there was no statistical significance in comparing the other Quisi parameters(including RL,NRP,SL,AT,SE,and S2 percent)between the two groups(P>0.05). Conclusion:SFD patients have a variety of clinical symptoms,and most of them show abnormal sleep EEG and ERP;EA can correct abnormal sleep EEG parameters and the MMN and P300 of ERP in SFD patients.

[Objective]To summarize the clinical experience of Professor CHEN Jian in treating periodic fever syndrome(PFS)in children from"latent fire".[Methods]Through outpatient follow-up study,collection of medical records and review of relevant literature,this paper summarized the etiology,pathogenesis and Professor CHEN's treatment experience of PFS in children from"latent fire",and a case was presented for verification.[Results]Professor CHEN believes that the core pathogenesis of PFS in children is"latent fire".Phlegm,poison and stasis are not only pathological products,but also important pathogenic factors throughout the course of the disease.Depression is the pathological state of the whole course of the disease.In the treatment,the method of supplementing Qi to remove heat or nourishing Yin to clear heat is used and combined with regulating Qi,and the self-prepared prescription is the effective treatment of PFS in children.The main symptom of the case was periodic fever,which was differentiated as Yin deficiency fever.The treatment of nourishing Yin and clearing heat,promoting Qi movement and relieving depression was applied,and good effect was achieved.[Conclusion]Professor CHEN's treatment of PFS in children from"latent fire"is effective,has certain guiding significance,and is worthy of clinical reference.

Objective:To analyze the clinical features of gastritis cystica profunda (GCP) and investigate the risk factors associated with its coexistence with gastric cancer.Methods:Data of 149 patients with pathologically confirmed GCP at Zhongshan Hospital of Fudan University between January 2015 and March 2022 were retrospectively analyzed for basic information, clinical data, lesion manifestations and pathological results, of which 106 were pathologically confirmed GCP after endoscopic resection and 43 others were pathologically confirmed GCP after surgical procedures. Among 149 patients, 56 were in the simple GCP group, and 93 in the GCP combined with gastric cancer group.Results:In the simple GCP group of 56 patients, 62.5% (35/56) were male and the mean age was 58.8 years. The predominant site of involvement was in the upper gastric segment (cardia and fundus) (51.8%,29/56), with manifestations primarily of the polypoid bulge type (41.1%,23/56) and submucosal bulge type (35.7%,20/56). Clinical symptoms were mostly atypical. In the group where GCP was combined with gastric cancer (93 cases), males accounted for 90.3% (84/93), the median age was 66.9 years, the upper gastric segment was predominantly affected (75.3%, 70/93), with differentiated cancer being the most common histological type (91.4%, 85/93). For 76 cases of early gastric cancer combined with GCP, mucosal lesions were the main presentation (73.7%, 56/76) with atypical clinical symptoms. Furthermore, in 17 cases of progressive gastric cancer combined with GCP, the manifestations were mainly bulging ulcers (88.2%, 15/17), and most of them were referred to the doctor because of abdominal pain and black stools (100.0%, 17/17). Binary logistic regression analysis showed that being male ( P=0.004, OR=4.411, 95% CI: 1.621-12.002), age ( P=0.001, OR=1.085, 95% CI: 1.036-1.136) and endoscopic manifestations of mucosal lesions ( P<0.001, OR=5.080, 95% CI: 2.162-11.939) were risk factors for GCP combined with gastric cancer, but involvement of the upper gastric segment was not related to combination with gastric cancer ( P=0.430, OR=0.707, 95% CI: 0.299-1.672). Among 106 patients with endoscopic resection, 57 cases of early gastric cancer combined with GCP had a median lesion length of 2.50 cm; 49 cases of GCP alone had a median lesion length of 1.20 cm, with significant difference ( Z=-5.503, P<0.001). All upper gastric GCP combined with early gastric cancer in endoscopically treated patients were cancers of the cardia, most of which were superficial elevation with the concave type (0-Ⅱa+Ⅱc) (44.7%, 21/47). 75.4% (43/57) patients with gastric cancer combined with GCP were graded as curative resection (eCuraA) after endoscopic surgery , and none of those who had additional surgery after endoscopic surgery had lymph node metastasis. There were 8 cases with history of gastric surgery, 7 of esophageal cancer, and 10 of multiple neoplastic gastric lesions in the 149 patients with GCP. Conclusion:GCP often occurs in the upper gastric region and is not inherently associated with the presence of gastric cancer. However, when coexisting with gastric cancer, it tends to affect elderly men, present with mucosal lesions of a differentiated histological type, and may be accompanied by esophageal or other gastric cancers. Notably, GCP is frequently identified as para-cancerous lesion, and endoscopic treatment emerges as a safe and effective approach, characterized by a high rate of curative endoscopic resections and a low incidence of lymphatic metastases.

Objective To analyze the evaluation results of health enterprises in Beijing City and their influencing factors. Methods A total of 40 enterprises that passed the health enterprise evaluation in Beijing from 2021 to 2022 were selected as the study subjects using the judgment sampling method. The total evaluation scores and influencing factors were analyzed based on the size, nature, industry classification, and establishment time of the enterprises. Results The total evaluation score of the 40 health enterprises was (553.1±18.4) points. Scores for the primary evaluation indicators, including management organization and system, occupational disease prevention measures, health environment, health promotion measures, prevention measures for occupational stress caused damage, and musculoskeletal injury prevention measures, were (94.0±4.8), (94.0±4.3), (94.5±3.8), (89.7±4.8), (89.6±4.6), and (91.4±5.9) points, respectively. The result of multiple linear regression analysis showed that, large enterprises had higher total evaluation scores than medium enterprises and micro and small enterprises after controlling for confounding factors such as industry classification and establishment time (all P<0.10). The total evaluation scores of private enterprises and foreign-funded enterprises were lower than that of state-owned or state-participated enterprises (all P<0.10). Conclusion Enterprise size and nature are influencing factors for the total evaluation score of health enterprises. It is necessary to enhance resource and policy support for medium-sized, micro and small enterprises and private enterprises to improve the development of the health enterprises.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To compare the aortic remodeling of the Fabulous stent system and standard thoracic aortic endovascular repair (TEVAR) on distal aorta type B aortic dissection (TBAD). Methods:The prospective data collected between Dec 2017 and Oct 2019 from 134 patients with type B aortic dissection (TBAD) who underwent treatment with the "Fabulous" stent system, and retrospective data from 159 TBAD patients receiving standard TEVAR from corresponding multicenter. By using propensity score matching analysis, we compared the prognosis and aortic remodeling outcomes in patients undergoing Fabulous and standard TEVAR treatments during a 1-year postoperative follow-up.Results:In this study, 62 patients in Fabulous group and 62 patients in standard TEVAR were included.There were no significant statistical differences in baseline characteristics between the two groups. In terms of aortic remodeling in bare stent region, Fabulous group had better change trends of diameter of true lumen [10.6 (4.4, 14.5) mm vs. 4.7 (0.9, 10.7) mm, P=0.001] and false lumen [-24.2 (-30.5, -4.9) mm vs. 0.7 (-11.8, 2.3) mm, P<0.001] than those in the standard TEVAR group. The rate of complete false lumen thrombosis was also higher in the Fabulous group (62.9% vs. 37.1%, P=0.042). Conclusion:The Fabulous stent system, when compared to standard TEVAR surgery, demonstrates good aortic remodeling outcomes in the distal aorta.