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*

Objective To analyze serum levels of long chain non coding RNA(lncRNA)ANRIL,CCR4-NOT transcription complex subunit 2(CNOT2)in breast cancer patients and their relationship with clinico-pathological characteristics and prognosis.Methods From February 2018 to February 2021,a total of 126 eld-erly patients with breast cancer in the hospital were selected as the breast cancer group.According to whether tumor progression occurred during follow-up,the patients were divided into poor prognosis group(n=26)and good prognosis group(n=100).60 old healthy female people who underwent physical examination during the same time were taken as control group.Statistical analysis was used to study the differences of serum lncRNA ANRIL and CNOT2 levels in patients with different clinical and pathological characteristics.The prognostic factors of elderly patients with breast cancer were conducted by Kaplan-Meier curve and Cox regression analy-sis.Receiver operating characteristic curve was drawn to assess the prognostic value of serum lncRNA ANRIL and CNOT2 in elderly patients with breast cancer.Results The levels of serum lncRNA ANRIL and CNOT2 in the breast cancer group were higher than those in the control group(P＜0.05).The serum lncRNA AN-RIL and CNOT2 levels in patients with TNM stage Ⅲ and histological grade Ⅲ were higher than those in pa-tients with TNM stage Ⅰ-Ⅱ and histological grade Ⅰ—Ⅱ(P＜0.05).The level of serum lncRNA ANRIL and CONT2 in poor prognosis group were higher than that in the good prognosis group(P＜0.05).The 3-year progression free survival rates of lncRNA ANRIL high and low expression group,CNOT2 high and low expression group were 66.67％(40/60),90.91％(60/66)and 66.13％(41/62),92.19％(59/64),respective-ly,with statistically significant differences(P＜0.05).TNM stage Ⅲ,histological grade Ⅲ,serum lncRNA ANRIL and CNOT2 were risk factors affecting the prognosis of elderly patients with breast cancer(P＜0.05).The area under the curve of serum lncRNA ANRIL and CNOT2 combined in assessment of prognosis in elderly patients with breast cancer was higher than that of lncRNA ANRIL and CNOT2 alone(P＜0.05).Conclusion The expression of serum lncRNA ANRIL and CNOT2 in elderly breast cancer are up-regulated,which are related to TNM stage and histological grading,and are markers to evaluate the prognosis of elderly patients with breast cancer.

Objective:To dry fresh Ginseng Radix et Rhizoma using different drying conditions; To investigate the effects of different drying conditions on the drying characteristics and medicinal quality of Ginseng Radix et Rhizoma.Methods:With moisture, powder color, extract, total polysaccharide and ginsenoside contents of Rg 1, Re, Rf, Rb 1, Rc, Rb 2 and Rd as indexes, the drying characteristics of Ginseng Radix et Rhizoma were studied based on Weibull function model, and the quality of Ginseng Radix et Rhizoma after drying was evaluated by entropy weight-TOPSIS model. Results:The drying method for Ginseng Radix et Rhizoma from its origin can be achieved by controlling the relative humidity of the drying medium to 50%, drying at 70 ℃ for 24 h, and then reducing the drying temperature to 60 ℃ until the moisture content was below 12.0%. This method could achieve high drying efficiency and produce high-quality Ginseng Radix et Rhizoma.Conclusions:The drying process of Ginseng Radix et Rhizoma is a falling rate process controlled by internal moisture diffusion. The drying rate of fresh Ginseng Radix et Rhizoma is affected by temperature and humidity. There is a certain correlation between the color of powder and the content of moisture, alcohol-soluble extractives and ginsenosides.

Objective To observe the clinical efficacy of Jin's triple-needle therapy combined with bilateral high-frequency repetitive transcranial magnetic stimulation in the treatment of post-stroke hemiplegia.Methods A total of 116 patients diagnosed with post-stroke hemiplegia and admitted to the wards and outpatient clinics of Yan'an City Hospital of Traditional Chinese Medicine from January 2023 to June 2024 were selected as the study subjects.The patients were randomly divided into an observation group and a control group using a random number table,with 58 patients in each group.The control group received bilateral high-frequency repetitive transcranial magnetic stimulation,while the observation group received Jin's triple-needle therapy in addition to the control group's treatment.After 30-day treatment,the clinical efficacy of the two groups was evaluated.Changes in traditional Chinese medicine(TCM)syndrome scores,Fugl-Meyer Assessment(FMA)scores for limb motor function,and Stroke-Specific Quality of Life(SS-QOL)scores were observed before and after treatment.Changes in neuron-specific enolase(NSE),glial fibrillary acidic protein(GFAP),and central nervous system-specific protein(S100-β)levels were compared between the two groups before and after treatment.The safety and incidence of adverse reactions in both groups were also evaluated.Results(1)The total effective rate in the observation group was 91.38%(53/58),compared to 75.86%(44/58)in the control group.The observation group showed significantly better efficacy than the control group,with a statistically significant difference(P＜0.05).(2)After treatment,both groups showed significant improvements in TCM syndrome scores and FMA scores for limb motor function(P＜0.05),and the observation group was significantly superior to the control group in improving TCM syndrome scores and FMA scores,with a statistically significant difference(P＜0.05).(3)After treatment,both groups showed significant improvementss(P＜0.05)in NSE,GFAP,and S100-β level,and the observation group was significantly superior to the control group in improving NSE,GFAP,and S100-β levels,with a statistically significant difference(P＜0.05).(4)After treatment,both groups showed significant improvements in SS-QOL scores for quality of life(P＜0.05),and the observation group was significantly superior to the control group in improving SS-QOL scores,with a statistically significant difference(P＜0.05).(5)The incidence of adverse reactions in the observation group was 12.07%(7/58),compared to 8.62%(5/58)in the control group.There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Jin's triple-needle therapy combined with bilateral high-frequency repetitive transcranial magnetic stimulation can significantly improve clinical symptoms,enhance limb motor function,reduce levels of brain injury markers,and improve the quality of life in patients with post-stroke hemiplegia.The treatment is safe and shows significant efficacy.

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.

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.

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.

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.

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.