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 investigate the effect of Zhuang medicine Adinandra nitida on blood pressure of hypertensive rats induced by N-nitro-L-arginine methyl ester(L-NAME).Methods L-NAME was used to induce hypertension rats model,they were divided into blank group,model group,captopril group,and high,medium,and low dose groups of Adinandra nitida.The rats were continuous gavaged for 4 weeks,and the blood pressures were measured once a week.Rats were anesthetized by intraperitoneal injection,blood samples and tissues were collected.Pathological changes of the rat thoracic aortic tissue were observed by hematoxylin eosin staining,the protein expression level of endothelial nitric oxide synthase(eNOS)in rat thoracic aorta was detected by western blotting,the content of eNOS in rat plasma was measured by enzyme linked immunosorbent assay and nitric oxide(NO)content in rat plasma was detected by one-step reduction method.Results Compared with model group,high and medium dose groups of Adinandra nitida and captopril group of rats showed significant reductions in systolic blood pressure and diastolic blood pressure(P<0.01),while there were no statistically significant change in heart rate(P>0.05).After 4 weeks of oral administration with Adinandra nitida,the damage of the vascular tissues of hypertensive rats induced by L-NAME had been improved,the expression of eNOS protein in thoracic aorta was significantly increased(P<0.01),and the contents of eNOS and NO in rat plasma were significantly increased(P<0.01).Conclusion Zhuang medicine Adinandra nitida has a hypotensive effect on L-NAME induced hypertensive rats,which may be related to the regulation of eNOS and NO.

Objective To report a case of Elizabethkingia anopheles(E.anopheles)-associated sepsis and menin-gitis,review the relevant literatures,and provide reference for the diagnosis and treatment of this infection.Methods Treatment process of a pediatric patient aged 11-year-7-month old who developed post-neurosurgery E.anophe-les-associated sepsis and meningitis was analyzed retrospectively.Relevant literature was reviewed to summarize clinical characteristics of patients with E.anopheles-associated sepsis or meningitis.Results The main clinical manifestations of this pediatric patient were fever and abnormal cerebrospinal fluid routine.The cerebrospinal fluid and blood cultures showed E.anopheles.Patient recovered after vancomycin treatment.Including this case,a total of 33 cases were analyzed,with 16 males and 1 unreported gender.The median age of patients was 49 years old(range:1 day-84 years).Most cases were healthcare-associated infections(62.5％,n=20)with underlying disea-ses,and 24 cases were cured.Conclusion E.anopheles-associated infections are rare in clinic,but can cause severe infections such as sepsis and meningitis,warranting clinical attention.

Objective To investigate the effect of Zhuang medicine Adinandra nitida on blood pressure of hypertensive rats induced by N-nitro-L-arginine methyl ester(L-NAME).Methods L-NAME was used to induce hypertension rats model,they were divided into blank group,model group,captopril group,and high,medium,and low dose groups of Adinandra nitida.The rats were continuous gavaged for 4 weeks,and the blood pressures were measured once a week.Rats were anesthetized by intraperitoneal injection,blood samples and tissues were collected.Pathological changes of the rat thoracic aortic tissue were observed by hematoxylin eosin staining,the protein expression level of endothelial nitric oxide synthase(eNOS)in rat thoracic aorta was detected by western blotting,the content of eNOS in rat plasma was measured by enzyme linked immunosorbent assay and nitric oxide(NO)content in rat plasma was detected by one-step reduction method.Results Compared with model group,high and medium dose groups of Adinandra nitida and captopril group of rats showed significant reductions in systolic blood pressure and diastolic blood pressure(P<0.01),while there were no statistically significant change in heart rate(P>0.05).After 4 weeks of oral administration with Adinandra nitida,the damage of the vascular tissues of hypertensive rats induced by L-NAME had been improved,the expression of eNOS protein in thoracic aorta was significantly increased(P<0.01),and the contents of eNOS and NO in rat plasma were significantly increased(P<0.01).Conclusion Zhuang medicine Adinandra nitida has a hypotensive effect on L-NAME induced hypertensive rats,which may be related to the regulation of eNOS and NO.

Objective To report a case of Elizabethkingia anopheles(E.anopheles)-associated sepsis and menin-gitis,review the relevant literatures,and provide reference for the diagnosis and treatment of this infection.Methods Treatment process of a pediatric patient aged 11-year-7-month old who developed post-neurosurgery E.anophe-les-associated sepsis and meningitis was analyzed retrospectively.Relevant literature was reviewed to summarize clinical characteristics of patients with E.anopheles-associated sepsis or meningitis.Results The main clinical manifestations of this pediatric patient were fever and abnormal cerebrospinal fluid routine.The cerebrospinal fluid and blood cultures showed E.anopheles.Patient recovered after vancomycin treatment.Including this case,a total of 33 cases were analyzed,with 16 males and 1 unreported gender.The median age of patients was 49 years old(range:1 day-84 years).Most cases were healthcare-associated infections(62.5％,n=20)with underlying disea-ses,and 24 cases were cured.Conclusion E.anopheles-associated infections are rare in clinic,but can cause severe infections such as sepsis and meningitis,warranting clinical attention.

Objective:To investigate the influencing of portal vein embolization (PVE) and PVE combined with transcatheter arterial chemoembolization (TACE) on secondary hepatectomy and prognosis of patients with initially unresectable hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 102 patients with initially unresectable HCC who were admitted to the Third Affiliated Hospital of Naval Medical University from October 26,2015 to December 31,2022 were collected. There were 82 males and 20 females, aged 52(range,25?73)years. Of 102 patients, 72 cases undergoing PVE combined with TACE were set as the PVE+TACE group, and 30 cases undergoing PVE were set as the PVE group. Observation indicators: (1) surgical resection rate of secondary hepatectomy and increase of future liver remnant (FLR); (2) situations of secondary hepatectomy; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Results:(1) Surgical resection rate of secondary hepatectomy and increase of FLR. The surgical resection rate of secondary hepatectomy in the PVE+TACE group and the PVE group were 72.2%(52/72) and 53.3%(16/30), respectively, showing no significant difference between the two groups ( χ2=3.400, P>0.05). The surgical waiting time, increasing volume of FLR, growth rate of FLR in the 52 patients of PVE+TACE group receiving secon-dary hepatectomy were 20(range, 14?140)days, 140(range, 62?424)mL, 9.8(range, 1.5?26.5)mL/day, respectively. The above indicators in the 16 patients of PVE group receiving secondary hepatectomy were 16(range, 12?35)days, 160(range, 95?408)mL, 10.5(range, 1.2?28.0)mL/day, respectively. There was no significant difference in the above indicators between the 52 patients of PVE+TACE group and the 16 patients of PVE group ( Z=1.830, 1.498, 1.266, P>0.05). (2) Situations of secondary hepatectomy. The operation time, rate of tumor necrosis (>90%, 60%?90%,<60%), cases with complications ≥ grade Ⅲa in the 52 patients of PVE+TACE group receiving secondary hepatectomy were 200(range, 125?420)minutes, 8, 4, 40, 28, respectively. The above indicators in the 16 patients of PVE group receiving secondary hepatectomy were 170(range, 105?320)minutes, 0, 0, 16, 4, respectively. There were significant differences in the above indicators between the 52 patients of PVE+TACE group and the 16 patients of PVE group ( Z=2.132, ?2.093, χ2=4.087, P<0.05). (3) Follow-up. Sixty-eight patients who completed the surgery were followed up for 40(range, 10?84)months. The 1-, 3-, 5-year recurrence free survival rate in the 52 patients of PVE+TACE group receiving secondary hepatectomy were 73.0%, 53.3%, 35.4%, respectively. The above indicators in the 16 patients of PVE group were 62.5%, 37.5%, 18.8%, respectively. There was a significant difference in the recurrence free survival rate between the 52 patients of PVE+TACE group and the 16 patients of PVE group ( χ2=4.035, P<0.05). The 1-, 3-, 5-year overall survival rate in the 52 patients of PVE+TACE group receiving secondary hepatectomy were 82.5%, 61.2%, 36.6%, respectively. The above indica-tors in the 16 patients of PVE group receiving secondary hepatectomy were 68.8%, 41.7%,20.8%, respectively. There was a significant difference in the overall survival rate between the 52 patients of PVE+TACE group and the 16 patients of PVE group ( χ2=4.767, P<0.05). Conclusion:Compared with PVE, PVE+TACE as stage Ⅰ surgery can increase the surgical resection rate of secondary hepatec-tomy and the recurrence free survival rate of patients with initially unresectable HCC, prolong the long-term survival time, but not influence the growth rate of FLR.

Objective:A microsurgical simulation training device based on real clinical scenes was designed and its effectiveness was tested.Methods:From January 1, 2020 to January 1, 2023, postgraduate students in the Plastic and Reconstructive Surgery Department of the First Medical Center of PLA General Hospital and the Plastic Surgery Hospital of Chinese Academy of Medical Sciences were enrolled in this prospective study. The simulation training device consists of four parts: (1)Blood perfusion system, which is used to simulate living animal blood vessels.(2)The inner baffling rod system, which is used to simulate the operation in deep cavity.(3) The exterior baffling rod system, which is used to simulate the operation in difficult positions.(4) A pulsating platform system is used to simulate microsurgery under the influence of respiratory movement. Preliminary verification of the effect of the simulated training device was as follows: Surgeons with no experience in microsurgery were completely randomized assigned to the control group (traditional microsurgery training group) and the experimental group (training group using the simulated training device). After 4 weeks of microsurgical training, the trainees were assigned to perform two surgical skill assessments, the first using a live animal model for end-to-end anastomosis of rat tail arteries, and the second assessment using end-to-end anastomosis of free latissimus dorsi flap arteries in a real case. The performance of the two groups was compared by using operation time and microsurgical GRS score scale including four items of dexterity, visuospatial ability, operative flow and judgment. Chi-squared test was used to analyze gender between the two groups. GRS scores between the two groups were compared by the Mann-Whitney U test. Participants’ ageand operation time between the two groups was compared by independent t-test. P<0.05 was considered statistically significant. Results:A total of 18 trainees were enrolled, including 10 in the control group, 6 males and 4 females, with an average age of (27.80±1.87) years. There were 8 subjects in the experimental group, 4 males and 4 females, with an average age of (28.10±1.56) years old. There were no significant differences in age, gender and other baseline characteristics between the two groups ( P>0.05). There was no significant difference in GRS score and operation time between the control group and the experimental group ( P> 0.05) in the first assessment. However, in the second assessment of real cases, the GRS score of the experimental group was significantly higher than that of the control group(14.25 vs. 5.70), and the operation duration of the experimental group was also shorter than that of the control group, and the difference was statistically significant[(100.37±24.65 ) min vs. (105.60±22.84) min] ( P<0.05). Conclusion:Compared with traditional microsurgery training methods, using microsurgery training devices based on clinical real scenes can effectively shorten the learning curve and enable trainees to master complex micromanipulation skills more quickly.

Objective:A microsurgical simulation training device based on real clinical scenes was designed and its effectiveness was tested.Methods:From January 1, 2020 to January 1, 2023, postgraduate students in the Plastic and Reconstructive Surgery Department of the First Medical Center of PLA General Hospital and the Plastic Surgery Hospital of Chinese Academy of Medical Sciences were enrolled in this prospective study. The simulation training device consists of four parts: (1)Blood perfusion system, which is used to simulate living animal blood vessels.(2)The inner baffling rod system, which is used to simulate the operation in deep cavity.(3) The exterior baffling rod system, which is used to simulate the operation in difficult positions.(4) A pulsating platform system is used to simulate microsurgery under the influence of respiratory movement. Preliminary verification of the effect of the simulated training device was as follows: Surgeons with no experience in microsurgery were completely randomized assigned to the control group (traditional microsurgery training group) and the experimental group (training group using the simulated training device). After 4 weeks of microsurgical training, the trainees were assigned to perform two surgical skill assessments, the first using a live animal model for end-to-end anastomosis of rat tail arteries, and the second assessment using end-to-end anastomosis of free latissimus dorsi flap arteries in a real case. The performance of the two groups was compared by using operation time and microsurgical GRS score scale including four items of dexterity, visuospatial ability, operative flow and judgment. Chi-squared test was used to analyze gender between the two groups. GRS scores between the two groups were compared by the Mann-Whitney U test. Participants’ ageand operation time between the two groups was compared by independent t-test. P<0.05 was considered statistically significant. Results:A total of 18 trainees were enrolled, including 10 in the control group, 6 males and 4 females, with an average age of (27.80±1.87) years. There were 8 subjects in the experimental group, 4 males and 4 females, with an average age of (28.10±1.56) years old. There were no significant differences in age, gender and other baseline characteristics between the two groups ( P>0.05). There was no significant difference in GRS score and operation time between the control group and the experimental group ( P> 0.05) in the first assessment. However, in the second assessment of real cases, the GRS score of the experimental group was significantly higher than that of the control group(14.25 vs. 5.70), and the operation duration of the experimental group was also shorter than that of the control group, and the difference was statistically significant[(100.37±24.65 ) min vs. (105.60±22.84) min] ( P<0.05). Conclusion:Compared with traditional microsurgery training methods, using microsurgery training devices based on clinical real scenes can effectively shorten the learning curve and enable trainees to master complex micromanipulation skills more quickly.

With rapid development of information technology,blended teaching model has gradually become mainstream teaching model in most colleges and universities.How to evaluate students'learning effect and analyze factors that affect students'per-formance is a key research direction of this teaching model.Taking blended teaching of Medical Immunology course in Xinxiang Medical University as an example,this paper introduces implementation process and evaluation system of blended teaching,analyzes main factors affecting students'performance and learning effect,and focuses on discussing influence of formative evaluation and"flipped classroom"on students'academic performance.

Objective To explore the clinical utility of endoclip papilloplasty in endoscopic retrograde cholangiopancreatography(ERCP).Methods A prospective study was conducted and selected 62 patients who underwent ERCP from November 2021 to November 2022.30 out of 32 patients who randomly underwent endoclip papilloplasty were successful.These patients were assigned to successful endoclip papilloplasty group(group A,n=30)or the duodenal papilla unclamping group(group B,n=30).The aim was to compare the difference in short-term and long-term complications between the two groups.Results The success rate of papillary plasty was 93.8%(30/32),with no statistically significant differences observed in the incidence of postoperative pancreatitis,postoperative hemorrhage after ERCP,and postoperative cholangitis between the two groups(P>0.05).The duodenal perforation rate was 0.There were no significant differences between the two groups in terms of total cholangitis incidence and recurrence rate of calculus of common bile duct within 1 year(P>0.05).However,there was a statistical difference in terms of total the incidence of cholangitis+calculus of common bile duct recurrence within 1 year(P<0.05).Conclusion The endoclip papilloplasty exhibits a high success rate and safety and feasibility procedure reducing long-term recurrence rate of cholangitis and calculus of common bile duct in endoscopic papillary large balloon dilation(EPLBD)procedure.