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

Nocardia is a Gram-positive pathogen responsible for causing dairy mastitis,which leads to purulent granulomatous lesions in mammary tissue and can significantly impact the dairy indus-try,resulting in substantial economic losses.To develop a rapid and accurate diagnostic method for detecting Nocardia of bovine origin,a conserved sequence of the 16S rRNA gene from Nocardia was selected from the NCBI database.Based on this sequence,a pair of primers and a TaqMan fluo-rescent quantitative probe were designed.The validation of the TaqMan fluorescence quantitative PCR(qPCR)method found in this study showed that the Ctvalue had a good linear relationship with recombinant plasmid concentrations ranging from 1×1010 to 1×102 copies/μL,with a regres-sion equation of y=-3.536x+43.78,a correlation coefficient(R2)of 0.997 5,a slope of-3.536,and an amplification efficiency(E)of 91％(where 90％＜E＜110％).The specificity was strong,with no cross-reactions with other pathogens.The standard curve had a high sensitivity with a low-er detection limit of 1 × 102 copies/μL,it was 100-fold higher than conventional PCR.The repeatability of the standard curve was also good.Both intra-and inter-group coefficients of varia-tion were below 2％.Using this method,234 milk samples and 80 environmental samples were tested using this method,respectively,with a positive detection rate of 27.07％,whereas conven-tional PCR had a positive detection rate of 19.43％,indicating that this method was more sensitive compared to conventional PCR.The fluorescent quantitative PCR detection method established in this study provides an effective means for the clinical detection of Nocardia in dairy cows.

Nocardia is a Gram-positive pathogen responsible for causing dairy mastitis,which leads to purulent granulomatous lesions in mammary tissue and can significantly impact the dairy indus-try,resulting in substantial economic losses.To develop a rapid and accurate diagnostic method for detecting Nocardia of bovine origin,a conserved sequence of the 16S rRNA gene from Nocardia was selected from the NCBI database.Based on this sequence,a pair of primers and a TaqMan fluo-rescent quantitative probe were designed.The validation of the TaqMan fluorescence quantitative PCR(qPCR)method found in this study showed that the Ctvalue had a good linear relationship with recombinant plasmid concentrations ranging from 1×1010 to 1×102 copies/μL,with a regres-sion equation of y=-3.536x+43.78,a correlation coefficient(R2)of 0.997 5,a slope of-3.536,and an amplification efficiency(E)of 91％(where 90％＜E＜110％).The specificity was strong,with no cross-reactions with other pathogens.The standard curve had a high sensitivity with a low-er detection limit of 1 × 102 copies/μL,it was 100-fold higher than conventional PCR.The repeatability of the standard curve was also good.Both intra-and inter-group coefficients of varia-tion were below 2％.Using this method,234 milk samples and 80 environmental samples were tested using this method,respectively,with a positive detection rate of 27.07％,whereas conven-tional PCR had a positive detection rate of 19.43％,indicating that this method was more sensitive compared to conventional PCR.The fluorescent quantitative PCR detection method established in this study provides an effective means for the clinical detection of Nocardia in dairy cows.

Objective To investigate the mechanism of inducing macrophage polarization induced by acupoint effect of electroacupuncture to promote the repair of acute skeletal muscle injury.Methods 45 SD rats were randomly divided into blank group,model group,electroacupuncture group(EA group),sodium chrominate group (DSCG group) and electroacupuncture+sodium chrominate group (hereinafter referred to as EA+DSCG group),with 9 rats in each group. The rats in the EA group and the EA+DSCG group were subjected to EA intervention at the right "Chengshan" (BL57) and "Yanglingquan"(GB34),with a frequency of 2 Hz/100 Hz. The gait changes of rats were recorded by animal gait analyzer. The morphological changes of the right gastrocnemius were observed by HE staining. The changes of mast cell aggregation and degranulation in local skin muscles of "chengshan" point were observed by toluidine blue staining. The expressions of Pax7,MyoD and skin mast cells and 5-HT in the right gastrocnemius were detected by immunofluorescence method. The positive expressions of CD68 and CD206 in right gastrocnemius macrophage was observed by immunohistochemical staining.Results Compared with blank group,the wiggle time of the right hind leg in model group and DSCG group increased,stride length decreased,HE staining showed inflammatory cell infiltration,myocyte enlargement,degeneration and necrosis. The degranulation rate of local skin mast cells in "Chengshan" (BL57) area increased,and the expressions of mast cell tryptase,5-HT,Pax7,MyoD,CD68 and CD206 increased (P<0.05). Compared with model group,the wiggle time of the right hind leg in EA group and EA+DSCG group decreased,stride length increased,HE staining showed that inflammatory cell infiltration was reduced,muscle cells were uniform in size and arranged neatly. Mast cell degranulation rate increased significantly in EA group,and the expressions of mast cell tryptase,5-HT,Pax7,MyoD and CD206 increased (P<0.05),while CD68 expression decreased (P<0.05). Compared with EA+DSCG group,the degranulation rate of mast cells and the expressions of mast cell tryptase,5-HT,Pax7,MyoD and CD206 increased (P<0.05),while CD68 expression decreased in EA group (P<0.05). Conclusion EA "Chengshan" (BL57) and "Yanglingquan" (GB34) can stimulate acupuncture points to locally induce mast cell degranulation,promote the polarization of macrophages,and then activate muscle satellite cells to play the regulatory process of repairing skeletal muscle injury.

Objective To analyze the morphological alterations of corpus callosum in children with spastic cerebral palsy(SCP)using three-dimensional magnetization prepared rapid acquisition gradient echo(3D-MPRAGE)technology and to investigate the correlation between morphological indexes and gross motor function.Methods Sagittal T1WI 3D-MPRAGE data was collected from 136 children with SCP(SCP group)and 132 age-and gender-matched healthy controls(HC)(HC group),and the gross motor function measure-88(GMFM-88)was applied to assess the gross motor function.Independent sample t-test was used to compare the corpus callosum surface area,volume,maximum anterior-posterior diameter,median sagittal area(total area and area of Ⅰ-Ⅴ zone)between the two groups.Partial correlation analysis was performed to calculate the correlation between morphological indexes of the corpus callosum and GMFM-88 with age as a covariate.Results Children under 3 years old,the corpus callosum surface area of the SCP group(3 914.51 mm2±1 207.97 mm2)was lower than that of the HC group(5 725.51 mm2±1 412.66 mm2).The volume of the corpus callosum(6 108.46 mm3±2 803.97 mm3)in the SCP group was lower than that of the HC group(11 297.96 mm3±4 109.02 mm3).Also,the maximum anterior-posterior diameter of the corpus callosum in the SCP group(53.40 mm±6.31 mm)was lower than that of the HC group(57.74 mm±6.04 mm)(all P<0.05).Children over 3 years old,the corpus callosum surface area of the SCP group(4 970.06 mm2±1 191.31 mm2)was lower than that of the HC group(6 372.55 mm2±1 445.59 mm2).The volume of the corpus callosum(8 330.20 mm3±2 888.20 mm3)in the SCP group was lower than that of the HC group(13 599.82 mm3±3 429.81 mm3)(all P<0.05).Partial correlation analysis showed significant correlation between corpus callosum volume,median sagittal area and gross motor score(P<0.01)with age as a covari-ate.Conclusion The 3D-MPRAGE technology can be useful for the comprehensive assessment of morphological alterations of the corpus callosum in SCP.The corpus callosum volume,and median sagittal area may become neuroimaging references for the assess-ment of motor development in cerebral palsy(CP).

Objective:To investigate the application value of right minimal invasive three-port technique of laparoscopic sleeve gastrectomy (RMIT-LSG) for the treatment of obesity.Methods:The retrospective and descriptive study was conducted. The clinical data of 66 obesity patients who underwent RMIT-LSG in the Sir Run Run Shaw Hospital of Zhejiang University School of Medicine from January to October 2021 were collected. There were 15 males and 51 females, aged 28.5(range, 16.0?54.0)years. The body mass index (BMI) of the 66 patients was (36.9±4.3)kg/m 2. There were 20 of the 66 patients combined with type 2 diabetes. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted using outpatient examination or the WeChat to detect postoperative recovery of patients including body mass changing, BMI and complications 6 months after operation. The follow-up was up to December 2021. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Surgical situations. All the 66 patients underwent RMIT-LSG successfully, without conversion to laparotomy or changing surgical method. The operation time and the volume of intraoperative blood loss of the 66 patients were (132±22)minutes and (14±8)mL, respectively. (2) Postoperative situations. The time to postoperative initial out-of-bed activities, time to postoperative first flatus, time to postoperative initial water intake, time to postoperative initial liquid food intake and duration of postoperative hospital stay of the 66 patients were (15±6)hours, (1.80±0.60)days, (1.00±0.20)days, (2.00±0.20)days and (3.40±0.60)days, respectively. Of the 66 patients, one case underwent post-operative abdominal hemorrhage at postoperative day 1 and received a second surgery for hemostasis. The patient with postoperative abdominal hemorrhage and other 65 patients recovered well without gastroparesis, gastric fistula, abdominal infection and other complication. (3) Follow-up. All the 66 patients were followed up for 6(range, 1?11)months. All the 66 patients completed the postoperative scar photography at postoperative 1 month, and results of scar photography showed concealed scar with good cosmetic effects. Twenty-seven of the 66 patients were followed up for 6 months after operation, with the weight loss, percentage of weight loss and decrease of BMI were (42±7)kg, 34.8%±2.9%, (14.2±1.9)kg/m 2, respectively. None of the 66 patient had innutrition during the follow-up. Conclusion:The RMIT-LSG is safe and feasible for the treatment of obesity, with a good cosmetic effect of the wound.

Objective:To explore the protective effect and mechanism of improved St. Thomas solution on canine skeletal muscle ischemia-reperfusion injury (IRI).Methods:Between March 2021 and September 2021, in the experimental operating room at the Air Force Hospital of the PLA Eastern Theater Command, 16 Beagles were randomly divided into control group, IRI group, IRI+NS group, and improved St. Thomas group, 4 in each group. The canine skeletal muscle IRI model was established, and the canine vital signs were monitored by pre-perfusion with improved St. Thomas perfusate [potassium chloride (KCl), magnesium sulfate (MgSO 4), and NaHCO 3 (pH adjusted)]. The pathological damage of canine skeletal muscle was explored by hematoxylin eosin (HE) staining, electron microscope detection and tissue wet/dry weight ratio, and blood vessel density. Hypoxia performances were detected by labeling blood vessels and hypoxia-inducible factor-1α (HIF-1α). The IRI model of L6 rat myoblasts was established, and the components of St. Thomas perfusion solution were pre incubated to explore the effect on the inhibition of cell proliferation. And by detecting reduced nicotinamide adenine dinucleotide phosphate (NADPH), F2 isoprostane (F2-isoprostane), interleukin 1β(IL-1β), tumour necrosis factor alpha (TNF-α), myeloperoxide enzyme (MPO), glutathione peroxidase (GSH-Px), etc. to explore its protective mechanism. Statistical software SPSS 23.0 was used for statistical analysis, A P<0.05 was set as statistically significant. Results:In the improved St. Thomas group, the vital signs of the dogs were relatively stable, the amount of maintained dopamine was less, the histopathological structure of the gastrocnemius muscle tended to be intact, the swelling of tissue cells and mitochondria was significantly relieved, and the tissue wet/dry weight ratio was less than that in the IRI group ( P=0.046). Pre-incubated with therapeutic doses of MgSO 4 or NaHCO 3, the proliferation rate of L6 cells was higher than that of IRI group ( P<0.01, P=0.005), NADPH ( P=0.004, P=0.001), F2-isoprostane ( P<0.01, P=0.01), IL-1β ( P=0.02, P=0.015), TNF-α ( P<0.01, P<0.01), MPO ( P<0.01, P<0.01) were all lower than those in the IRI group, except GSH-Px that was higher than what in the IRI group ( P<0.01). Conclusion:Pre-perfusion of the improved St. Thomas solution can stabilise the vital signs of dogs in a short period of time. The solution can improve the state of skeletal muscle cells, improve tissue hypoxia, and reduce the damage of skeletal muscle tissue cells through anti-inflammatory and anti-oxidative stress.

Objective:To explore the early outcomes surgical treatment with growing rod for idiopathic early-onset scoliosis (IEOS).Methods:Data of 11 patients with IEOS who had surgical treatment from February 2017 to December 2018 were retrospectively analyzed. There were 4 males and 7 females aged 6.45±1.63 at the time of the first operation, with preoperative Cobb angle of 74.74°±6.48° (range, 66.12°-87.85°). The imaging data and clinical data before operation, after operation instantly, 1 month after operation, 1 year after operation and 2 years after operation, and surgical-related complications were analyzed and recorded.Results:All the 11 patients were followed up for 28.82±4.77 months. The Cobb angle was 74.74°±6.48° before the initial implantation of internal fixation, and decreased to 30.30°±4.04° immediately after the operation, 30.39°±4.49° 1 month after the operation, 26.93°±3.09° 1 year after the operation, and 28.36°±2.98° 2 years after the operation. The correction rate was 61.82%±4.85% 2 years after operation. The height of T 1-T 12 thoracic vertebra was 13.69±2.05 cm before surgery, and increased to 20.74±3.10 cm immediately after surgery, and was 20.85±3.62 cm 1 month after surgery, 21.49±3.56 cm 1 year after surgery, and 22.54±3.63 cm 2 years after surgery. The height of T 1-S 1 vertebral body was 24.21±3.20 cm before surgery, and increased to 31.04±3.79 cm immediately after surgery, and was 30.85±3.64 cm 1 month after surgery, 32.91±3.24 cm 1 year after surgery, and 34.46±3.28 cm 2 years after surgery. Preoperative apical vertebral translation (AVT) was 7.45±2.00 cm before the initial operation, and shortened to 2.04±0.67 cm immediately after the operation, 2.07±0.70 cm 1 month after the operation, 2.24±0.57 cm 1 year after the operation, and 2.11±0.82 cm 2 years after the operation. There were statistically significant differences in the above indexes before surgery, 1 month after surgery, 1 year after surgery and 2 years after surgery. Compared with preoperation, pulmonary function FEV1 and FVC increased to 1.28±0.13 L and 1.49±0.10 L, respectively, 1 year after surgery, and 1.34±0.13 L and 1.54±0.12 L, respectively, 2 years after surgery. Pulmonary function was significantly improved 1 year after surgery, and pulmonary FVC was positively correlated with T 1-T 12 thoracic vertebral height ( r=0.838, P< 0.001). 13 complications were found in the 11 patients, including 2 cases of proximal screws loosening, 1 case of proximal junction kyphosis, 1 case of titanium rod fracture, 3 cases of skin swelling cause by internal fixation, and 6 cases of subcutaneous effusion, with good results after timely treatment. Conclusion:The traditional growing rod can effectively control the progression of deformity in patients with IEOS, maintain the growth and development of trunk, and promote the development and maturation of lung function.

Acute respiratory failure due to acute hypoxemia is the major manifestation in severe coronavirus disease 2019 (COVID-19). Rational and effective respiratory support is crucial in the management of COVID-19 patients. High-flow nasal cannula (HFNC) has been utilized widely due to its superiority over other non-invasive respiratory support techniques. To avoid HFNC failure and intubation delay, the key issues are proper patients, timely application and improving compliance. It should be noted that elder patients are vulnerable for failed HFNC. We applied HFNC for oxygen therapy in severe and critical ill COVID-19 patients and summarized the following experiences. Firstly, to select the proper size of nasal catheter, to locate it at suitable place, and to confirm the nose and the upper respiratory airway unobstructed. Secondly, an initial ow of 60 L/min and 37℃ should be given immediately for patients with obvious respiratory distress or weak cough ability; otherwise, low-level support should be given first and the level gradually increased. Thirdly, to avoid hypoxia or hypoxemia, the treatment goal of HFNC should be maintained the oxygen saturation (SpO) above 95% for patients without chronic pulmonary disease. Finally, patients should wear a surgical mask during HFNC treatment to reduce the risk of virus transmission through droplets or aerosols.
Aged ; Betacoronavirus ; isolation & purification ; Cannula ; Coronavirus Infections ; therapy ; Humans ; Oxygen ; administration & dosage ; Pandemics ; Pneumonia, Viral ; therapy

Acute respiratory failure due to acute hypoxemia is the major manifestation in severe coronavirus disease 2019 (COVID-19) induced by severe acute respiratory syndrome coronavirus 2 infection. Rational and effective respiratory support is crucial in the management of COVID-19 patients. High-flow nasal cannula (HFNC) has been utilized widely due to its superiority over other non-invasive respiratory support techniques. To avoid HFNC failure and intubation delay, the key issues are proper patients, timely application and improving compliance. It should be noted that elder patients are vulnerable for failed HFNC. We applied HFNC for oxygen therapy in severe and critical COVID-19 patients and summarized the following experiences. Firstly, to select the proper size of nasal catheter, to locate it at suitable place, and to confirm the nose and the upper respiratory airway unobstructed. Secondly, an initial flow of 60 L/min and 37℃ should be given immediately for patients with obvious respiratory distress or weak cough ability; otherwise, low-level support should be given first and the level gradually increased. Thirdly, to avoid hypoxia or hypoxemia, the treatment goal of HFNC should be maintained the oxygen saturation (SpO) above 95% for patients without chronic pulmonary disease. Finally, patients should wear a surgical mask during HFNC treatment to reduce the risk of virus transmission through droplets or aerosols.
Aged ; Betacoronavirus ; Cannula ; Coronavirus Infections ; complications ; therapy ; Humans ; Hypoxia ; etiology ; prevention & control ; therapy ; Masks ; Oxygen ; administration & dosage ; Oxygen Inhalation Therapy ; instrumentation ; standards ; Pandemics ; Pneumonia, Viral ; complications ; therapy