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

BACKGROUND: Telesurgery has the potential to overcome spatial limitations for surgeons, which depends on surgical robot and the quality of network communication. However, the influence of network latency and bandwidth on telesurgery is not well understood. METHODS: A telesurgery system capable of dynamically adjusting image compression ratios in response to bandwidth changes was established between Beijing and Sanya (Hainan province), covering a distance of 3000 km. In total, 108 animal operations, including 12 surgical procedures, were performed. Total latency ranging from 170 ms to 320 ms and bandwidth from 15-20 Mbps to less than 1 Mbps were explored using designed surgical tasks and hemostasis models for renal vein and internal iliac artery rupture bleeding. Network latency, jitter, frame loss, and bit rate code were systemically measured during these operations. National Aeronautics and Space Administration Task Load Index (NASA-TLX) and a self-designed scale measured the workload and subjective perception of surgeons. RESULTS: All 108 animal telesurgeries, conducted from January 2023 to June 2023, were performed effectively over a total duration of 3866 min. The operations were completed with latency up to 320 ms and bandwidths as low as 1-5 Mbps. Hemostasis for vein and artery rupture bleeding models was effectively achieved under these low bandwidth conditions. The NASA-TLX results indicated that latency significantly impacted surgical performance more than bandwidth and image clarity reductions. CONCLUSIONS This telesurgery system demonstrated safety and reliability. A total of 320 ms latency is acceptable for telesurgery operations. Reducing image clarity can effectively mitigate the potential latency increase caused by decreased bandwidth, offering a new method to reduce the impact of latency on telesurgery.
Animals ; Robotic Surgical Procedures/methods* ; Laparoscopy/methods*

Intracranial atherosclerosis has been regard as the most common cause of ischemic stroke.The information of the types and degree of vascular wall lesions is important basis for the diagnosis and treatment of ischemic stroke.High-resolution MR vessel wall imaging can directly display the lumen and wall of intracranial vessels,evaluate the characteristics of atherosclerotic plaque qualitatively and quantitatively,including intra-plaque hemorrhage,plaque enhancement,and plaque distribution.Thus,high-resolution MR vessel wall imaging may play an important role in risk stratification,pathogenesis,treatment and prognosis evaluation in ischemic stroke patients.This review summarizes the progress of high-resolution MRI vessel wall imaging in the evaluation of intracranial atherosclerosis,especially the pathogenesis of plaque features and treatment-related information.

Objective To investigate the feasibility and clinical significance of membrane anatomy theory in the application of thoracoscopic and laparoscopic radical esophageal resection.Methods A retrospective analysis was performed on 142 cases of thoracoscopic and laparoscopic radical esophagectomy based on membrane anatomy theory from December 2018 to October 2021.The esophageal mesangium,esophageal cancer,and nerves,blood vessels,lymphatic system,adipose tissue,upper stomach,left mesangium,and left gastric lymph nodes in the esophageal mesangium were removed as a whole.During the surgery,the space containing loose connective tissue around the esophagus was seen to be the esophageal fascial fusion space.The first 10 cases were labeled with nanocarbon tracer markers,showing esophageal lymphatic drainage to the left gastric lymph node.Results All the 142 patients had smooth surgery.The operation time was 150-230 min(mean,184.6±21.3 min),the intraoperative blood loss was 20-100 ml(mean,46.7±16.8 ml),the number of lymph nodes dissected was 12-41(mean,23.5±7.3),and the positive lymph nodes were found in 97 cases.The postoperative chest drainage time was3-10 d(mean,7.1±2.5 d),the postoperative oral intake time was 5-10 d(mean,7.6±1.7 d),and the total hospital stay was 9-20 d(mean,14.0±4.6 d).The total incidence of postoperative complications was 21.8%(31/142),including 7 cases(4.9%)of anastomotic leakage,9 cases(6.3%)of anastomotic stenosis,9 cases(6.3%)of hoarseness,and6 cases(4.2%)of residual gastritis.There was no postoperative bleeding,chyllevial leakage,infection,or death within 30 d after surgery.The follow-ups of the 142 patients lasted for 11-35 months,with a median of 26 months,and there was no recurrence and death.Conclusions There is a mesangial structure that constitutes an"envelope"around the esophagus.The membrane anatomy theory is suitable for the treatment of esophageal cancer,and radical resection of esophageal cancer based on the theory is safe,effective,and feasible.

Venous thromboembolism (VTE), comprising both deep vein thrombosis and pulmonary embolism, is a chronic illness that contributes significantly to the global burden of disease. The American College of Chest Physicians (ACCP) published the 9th edition of antithrombotic treatment guidelines for VTE (AT9) in 2012, which was first updated in 2016. In October 2021, ACCP published the 2nd update to AT9, which addressed 17 clinical questions related to VTE and presented 29 guidance statements in total. In this paper we interpreted the recommendations proposed in this update of the guidelines.

ObjectiveTo investigate the intestinal absorption characteristics of multi-index components in Danggui Buxuetang with drug absorption simulating system （DASS） established by everted intestinal sac model. MethodThe intestinal absorption solution at different time points after administration of Danggui Buxuetang was collected and detected by high performance liquid chromatography （HPLC）， acetonitrile （A）-0.2% glacial acetic acid solution （B） was used as the mobile phase for gradient elution （0-16 min， 15%-23%A； 16-20 min， 23%-28%A； 20-25 min， 28%-30%A； 25-30 min， 30%A； 30-35 min， 30%-65%A； 35-45 min， 65%-95%A）， the detection wavelength was 302 nm. HPLC fingerprint of intestinal absorption solution was established and the common peak was calibrated， and the relative cumulative absorption rate of each index component was calculated. The relative cumulative absorption curves of components were fitted with various mathematical models by DDSolver 1.0 to explore the absorption law of different components. ResultThe absorption process of C2 （calycosin-7-glucoside） and C6 in Danggui Buxuetang was in line with zero-order equation， C9 was best fitted by Weibull equation， and the remaining 7 components were in line with Makoid-Banakar equation. C1 with C2， C3， C5， C7 and C10， C2 with C5 and C7， C3 with C4， C5， C7 and C10， C4 with C6 and C10， C5 with C7， C6 with C10， C7 with C10， C8 with C9 were absorbed simultaneously during the absorption process. With the prolongation of time， the overall cumulative absorption rate of Danggui Buxuetang increased. At 120 min， the overall cumulative absorption rate of Danggui Buxuetang exceeded 38%， and reached 49.14% at 180 min. ConclusionTen ingredients in Danggui Buxuetang are absorbed in the jejunum， but absorption law of various components is different， which shows that the intestinal absorption of compound preparations of traditional Chinese medicine （TCM） has multiple characteristics. Intestinal absorption study of TCM compound preparations with chemical composition as the index can reveal some of its absorption law， but it is not complete.

Objective:To investigate the influences of SCN3A gene polymorphism(c.905A>G/p.N302S and c. 1441C>T/p.L481L) on the efficacy of valproic acid sodium in the treatment of Zhuangzu epilepsies.Methods:Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)technique and the way of direct sequence, the SCN3A gene c. 905A>G/p.N302S and c. 1441C>T/p.L481L genotypes in peripheral blood were detected in 244 epileptic patients (85 cases in effective group and 139 cases of ineffective group) in the standardized treatment of valproic acid sodium.The blood concentration of valproic acid sodium was detected by LC-MS.Evaluating the correlation between the genotype and alleles of two groups of patients and the efficacy of valproic acid sodium and analyzing the difference of valproic acid sodium's blood concentration between different genotypes.The linkage disequilibrium of c. 905A>G/p.N302S and c. 1441C>T/p.L481L were analyzed by software SHEsis.Results:The allele and genotype distribution in c. 905A>G/p.N302S loci between effective group(A, G allele: 50.6%, 49.4%, AA, AG, GG genotype: 27.1%, 47.1%, 25.8%) and ineffective group(A, G allele: 37.4%, 62.6%, AA, AG, GG genotype: 16.6%, 41.7%, 41.7%) had statistically significant difference(χ 2=7.501, P=0.006; χ 2=7.907, P=0.019). There was no significant difference in allele and genotype distribution of c. 1441C>T/p.L481L loci between effective group(C, T allele: 47.1%, 52.9%, CC, CT, TT genotype: 23.5%, 47.1%, 29.4%) and ineffective group(C, T allele: 38.8%, 61.2%, CC, CT, TT genotype: 18.7%, 40.3%, 41.0%)(χ 2=2.920, P=0.088; χ 2=3.099, P=0.212). Compared with the AA + AG genotype, the GG genotype at c. 905A>G/p.N302S locus significantly reduced the efficacy of valproic acid sodium ( OR=2.051, 95% CI=1.136-3.703). Compared with genotypes AA+ AG, there were no significant differences in blood concentration of genotype GG of c. 905A>G/p.N302S ( t=3.256, P=0.137). Compared with genotypes CC+ CT, there were no significant differences in blood concentration of genotype TT of c. 1441C>T/p.L481L( t=4.628, P=0.082). c.905A>G/p.N302S and c. 1441C>T/p.L481L were without linkage disequilibrium. Conclusion:These results suggest that the single nucleotide polymorphisms of c. 905A>G/p.N302S in SCN3A genes may play a role in the resistivity of valproic acid sodium in Zhuangzu epilepsies.

Objective: Intraperitoneal chemotherapy is increasingly being used in the treatment of gastric cancer with peritoneal me-tastasis, because the drug can directly act on the metastatic nodules. Repeated treatment can be administered through implanted ports, provided the ports are appropriately managed. Our study aimed to investigate the safety of peritoneal port implantation in pa-tients with gastric cancer with peritoneal metastasis. Methods: We retrospectively reviewed the records of patients undergoing intra-peritoneal port implantation for the administration of chemotherapy between June 2015 and June 2018 to investigate the causes of complications and to discuss their management and prevention. Results: Fifty-five ports were implanted in 54 patients with median us-age time of 8.4 (0.8-32.0) months. Complications occurred at 13 port sites (23.6%), including obstruction (7.3%), severe pain (5.5%), in-fection (3.6%), reflux (3.6%), access difficulty (1.8%), and subcutaneous mass formation (1.8%). The median interval from the time of port implantation to the development of complications was 2.1 months. No factor contributing to the complications was identified (P>0.05). Conclusions: Peritoneal port implantation to systematic chemotherapy in patients with gastric cancer with peritoneal metastasis is safe and feasible if the ports can be carefully managed.

Objective To investigate the effect of aerobic exercise combined with Levocarnitine in treating stable angina pectoris ( SAP ) and its effect on vascular endothelial function and serum levels of superoxide dismutase ( SOD ), total antioxidant capacity ( TAC ), glutathione peroxidase ( GSH-px ), malondialdehyde (MDA),and lipid peroxide( LPO) . Methods One hundred and fifty patients with SAP were selected in Affiliated Hospital of Yan′an University from september 2017 to september 2018 and randomly divided into control group and observation group( 75 cases in each group) . Both groups received routine intervention according to the guidelines. The control group was given with intravenous drip of left carnitine(3 g／time and once a day). On basis of the control group,the observation group was treated with regular aerobic exercise therapy. After 8 weeks＇ treatment for two groups,attack frequency degree of angina pectoris,score of life quality of Seattle angina scale(SAQ),and clinical effect were compared between the two groups. And the vascular endothelial function ( plasma endothelin ( ET ) 1, nitric oxide ( NO )), flow mediated vasodilation(FMD) of brachial artery and antioxidant effect(serum levels of SOD,TAC,GSH-px, MDA and LPO) were detected. Results After 8 weeks＇treatment,frequency of angina pectoris and episode of duration of angina pectoris in the observation group were less(( 4. 19± 0. 56) vs. ( 6. 22 ± 0. 89) time, (4. 31±0. 50) vs. (5. 25±0. 71) min),while life quality indexes SAQ score was higher,than those in the control group,and the difference was statistically significant (( 18. 44 ± 2. 30) vs. ( 12. 49 ± 1. 82) score, (56. 31±6. 62) vs. (48. 05± 5. 88) score,(14. 46 ± 1. 99) vs. ( 9. 22 ± 1. 10) score,( 21. 41 ± 2. 95)) vs. (18. 09±2. 26) score,(16. 14±2. 17) vs. (12. 05±1. 82) score,(all P＜0. 01)). The total clinical effective rate of the observation group ( 92%( 69 ／ 75)) was higher than that of the control group ( 80%( 60 ／75)),the difference was statistically significant (χ2＝4. 485,P＝0. 034). After 8 weeks′ treatment,level of ET-1,FMD of brachial artery,MDA,and LPO were lower than those in the control group(( 65. 38± 7. 91) ng／L vs. (77. 12±8. 56) ng／L,( 9. 44± 1. 34)% vs. ( 12. 55± 1. 81)%,(2. 81± 0. 43) μmol／L vs. ( 3. 90 ±0. 50) μmol／L,(3. 14±0. 44) μmol／L vs. (4. 40± 0. 63) μmol／L),while NO,SOD,TAC,GSH-px were higher than control group(( 67. 51 ± 7. 79) μmol／L vs. ( 52. 17± 6. 08) μmol／L,( 85. 25± 9. 67) U／L vs. (76. 01±8. 33) U／L,(12. 79±1. 80) kU／L vs. (9. 64±11. 05) kU／L,(117. 65±15. 03) U／L vs. (111. 76 ±14. 19) U／L),and the difference was statistically significant (all P＜0. 01). Conclusion Aerobic exercise combined with Levocarnitine in treating SAP can reduce the attack of angina pectoris, improve the life treatment of patients,and improve the clinical effect,which may be related to the improvement of endothelial function and antioxidant effect.

Objective To observe the effects of proximal gastric electrical stimulation (GES) on body weight and gastrointestinal motility in SD rats,and investigate the regulation of gastric nerve stimulation and serum gastrointestinal hormones by neuro-humoral regulation.Methods 12 SD rats were divided into experimental group (n =6) and control group (n =6),with gastric electrical stimulator implanted,and in experimental group dual-channel GES was activated.General status was observed for 4 weeks after GES activation,including body weight,feeding and water intake,urine and stool volumes,the resting gastric volume and gastric emptying were monitored via the establishment of intestinal fistula,and serum gastrointestinal hormones change was detected.Results During 4-week GES process,one rat had gastric retention and died at 1 week after GES activated.Compared with the control group,body weight,food intake,urine and stool volumes levels of the rats in experimental group decreased significantly (t =4.005,2.530,3.350,all P＜0.05).Resting gastric volume was significantly lower than that in the control group [(2.93 ± 0.50) ml vs.(5.10 ± 0.53) ml,Z =2.460,P =0.014],and the intestinal juice drainage was lower than the control group [(0.18 ±0.15)ml vs.(0.44 ±0.05)ml,Z =2.513,P =0.012],while serum GLP-1 levels were similar between the two groups [(0.44 ± 0.05) ml vs.(0.18 ± 0.15) ml,Z =1.026,P =0.305],but Ghrelin was significantly higher than that in the control group [(1.65 ± 0.58) vs.(0.65 ±0.36),Z =2.380,P =0.017].Conclusion The proximal GES may lead to the change of the body weight,food intake,gastrointestinal function and motility,possibly by stimulating nerve reflex inducing gastrointestinal hormones secretion and affect gastrointestinal function.