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 antidepressant effect and potential mechanism of icariside Ⅱ （ICSⅡ） based on the GABAergic nervous system. METHODS The male Kunming mice were randomly divided into a control group （group C， 10 mice） and a modeling group （50 mice）. The depression model was induced by chronic unpredictable mild stress （CUMS） method in the modeling group. After 21 days of stimulation， the rats of modeling group were randomly divided into depression model group （NS group）， positive control group [ECS group， oxalate escitalopram 15 mg/（kg·d）] and ICSⅡ low-dose， medium-dose and high-dose groups [ICSⅡ-L group， ICSⅡ-M group， ICSⅡ-H group； ICSⅡ 10， 20， 30 mg/（kg·d）]， with 10 mice in each group. Administration groups were given relevant medicine intragastrically， once a day， for 14 consecutive days. The sugar water preference rate， total exercise distance， immobility time in tail suspension and forced swimming experiments were detected in each group. The morphology of neurons and Nissl bodies in the hippocampal CA3 region were observed； the contents of γ-aminobutyric acid （GABA） and glutamic acid （Glu）， GABA/Glu ratio， and the expressions of GABAergic nervous system-related proteins （GABA A receptor α1， GABA B receptor 1， vesicular GABA transporter， glutamate decarboxylase 67， GABA membranal transporter 3） were detected in hippocampus. RESULTS Compared with group C， the sugar water preference rate and the total exercise distance significantly reduced in NS group， while the values of immobility time in the tail suspension test and forced swimming test were significantly prolonged （P＜0.05）. The morphology of neurons in the CA3 area of the hippocampus was irregular and the Nissl bodies were reduced， with a significant decrease in the number of structurally intact neurons （P＜0.05）； the content of Glu was significantly increased， while the content of GABA， GABA/Glu ratio， and the expressions of GABAergic nervous system-related proteins were significantly decreased （P＜0.05）. Compared with NS group， depression behavior in each administration group was improved， and the above indexes were mostly reversed （P＜0.05）. CONCLUSIONS ICSⅡ can improve depression behavior of depression model mice. The mechanisms may be associated with regulating the balance of GABA and Glu， increasing the synthesis， transport and release of GABA， and regulating the expressions of GABA-related receptors， so as to improve GABAergic nervous system.

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 discuss the effects of walking function-guided interactive Tuina(Chinese therapeutic massage)on spatiotemporal gait parameters in children with spastic cerebral palsy(CP). Methods:Fifty children with spastic diplegic CP were divided into an observation group and a control group following a paired design and random number principle,with 25 cases in each group.The observation group was treated with the walking function-guided interactive Tuina,and the control group was offered the"six methods of spine and back"Tuina,20 min for each session and 5 sessions weekly for 3 consecutive months.The children's changes were assessed using the percentage of dimension E(walking,running,and jumping)of the gross motor function measure-88(GMFM-88)and three-dimensional gait analysis. Results:After treatment,the percentage of GMFM-88 dimension of dimension E(walking,running,and jumping)changed significantly in both groups(P<0.05),and the between-group difference was also statistically significant(P<0.05).After treatment,the step length,walking speed,and step frequency changed markedly in the observation group(P<0.05)and were significantly different from those in the control group(P<0.05).After the intervention,the stance phase and double support extended,and the swing phase became shorter in the observation group(P<0.05);the between-group differences were statistically significant(P<0.05).The maximal knee flexion angle and maximal posterior pelvic tilt angle decreased After treatment in the observation group,and the maximal anterior pelvic tilt angle increased,all showing statistical significance(P<0.05);the between-group differences were statistically significant(P<0.05). Conclusion:Compared with the passive Tuina manipulations,the"six methods of the spine and back",walking function-guided interactive Tuina has its advantage in improving walking function in children with spastic CP,manifesting as better lower-limb force line and walking efficiency.

Objective:To observe the clinical efficacy of neck Gongfa exercise in intervening people at high risk for cervical spondylosis. Methods:A total of 212 participants from 8 companies at high risk for cervical spondylosis were divided into two groups using the random number table method,with 105 participants in the control group receiving health education and 107 participants in the trial group receiving an additional neck Gongfa exercise.After successive 3-month interventions,the two groups were compared in terms of cervical soft tissue tension and neck disability index(NDI)score.The incidence of cervical spondylosis was observed 3 months later. Results:During the process,10 cases dropped out in the trial group,and the control group had 9 dropout cases.After the intervention,the cervical soft tissue tension value and NDI score improved in both groups(P<0.05)and showed significant differences between the two groups(P<0.05).At the 3-month follow-up,the trial group had a lower incidence rate of cervical spondylosis than the control group(P<0.05). Conclusion:For people at high risk for cervical spondylosis,neck Gongfa exercise can effectively improve cervical soft tissue tension and motor dysfunction and lower the incidence of cervical spondylosis in the short run.

Objective:To observe the clinical efficacy of treating somatoform pain disorder(SPD)with electroacupuncture(EA)at the Governor and Conception Vessel points plus duloxetine.Methods:Eighty-two SPD patients were randomly allocated to an observation group and a control group,with 41 cases in each group.The control group was intervened by oral administration of duloxetine hydrochloride enteric capsules at a dose of 60 mg per time once a day;based on the medication,the observation group received additional EA treatment by selecting points from the Governor and Conception Vessels.Clinical efficacy was evaluated after 8 weeks of treatments;changes in the scores of the short-form McGill pain questionnaire(SF-MPQ),self-report symptom inventory,symptom check list-90(SCL-90),Pittsburgh sleep quality index(PSQI),and generic quality of life inventory-74(GQOLI-74)were also compared.Results:After the intervention,the observation group surpassed the control group in comparing the total effective rate(P＜0.05).The SF-MPQ score,SCL-90 somatization score,and PSQI score dropped notably in both groups after treatment,and the intra-group differences were statistically significant(P＜0.05);the three scores were significantly lower in the observation group than in the control group(P＜0.05).The GQOLI-74 score got an increase in each dimension in both groups after treatment,and the intra-group differences were also statistically significant(P＜0.05);the GQOLI-74 dimension scores were all significantly higher in the observation group than in the control group(P＜0.05).Conclusion:For patients with SPD,combining EA at the Governor and Conception Vessel points and duloxetine hydrochloride enteric capsules can markedly improve their clinical symptoms and quality of life.

Objective    To compare the outcomes following emergency surgery or conservative treatment for patients with acute type A aortic intramural hematoma (IMH). Methods    Clinical data of consecutive patients diagnosed with acute type A aortic IMH in our hospital from September 2014 to December 2018 were retrospectively analyzed. The patients who met our surgical indications received surgery (an operation group) and other patients received strict conservative treatment (a conservative treatment group). Results    Finally 127 patients were enrolled, including 112 males and 15 females with an average age of 53.6±13.0 years. Of 127 patients, 85 (66.9%) patients accepted emergency surgery and 42 (33.1%) patients accepted strict conservative treatment. There was no difference between the two groups in early mortality or complications (P>0.05). The 5-year survival rate was 90.4% in the operation group and 74.3% in the conservative treatment group (P=0.010). A maximum aortic diameter in the ascending aorta and aortic arch≥45 mm and maximum thickness of IMH in the same section≥8 mm were risk factors for IMH-related death in patients undergoing conservative treatment (P<0.001). Conclusion    The mortality associated with emergency surgery for patients with acute type A aortic IMH is satisfactory. In clinical centers with well-established surgical techniques and postoperative management, emergency surgical treatment may provide a better outcome than conservative treatment for patients with acute type A aortic IMH.

Objective:To explore the clinical and imaging characteristics of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) caused by mitochondrial DNA 14453G>A (m.14453G>A) mutation.Methods:A case of MELAS caused by m.14453G>A mutation in the First Affiliated Hospital of Harbin Medical University on October 12, 2021 was reported. At the same time, the reported cases of MELAS and Leigh syndrome (LS) caused by the m.14453G>A mutation were reviewed. This enabled a comprehensive summarization, analysis, and comparison of these cases.Results:The patient was a female. She has suffered from the disease since 13-year old with seizures, accompanied by the disturbance of mood and the loss of memory. Brain magnetic resonance imaging findings consisted of lesions in frontal, parietal, occipital, temporal lobe and cerebellar. The patient was initially considered with autoimmune encephalitis and posterior reversible encephalopathy syndrome. Since direct sequencing of the complete mitochondrial genome from blood of the patient revealed m.14453G>A mutation in ND6 gene, and the mutation rate was 17.0%, the patient eventually diagnosed with MELAS based on clinical manifestations, imaging examinations, and genetic testing results. Using "m.14453G>A" as the search term, the relevant literature in China and abroad was retrieved and those with complete clinical data were identified. A total of 11 cases of m.14453G>A mutation including this case were reported, of whom 5 patients were diagnosed as MELAS, and 6 patients were diagnosed as LS. Among the 11 patients, those being adolescent or adult and with lesions in the cortex and subcortical white matter were probably be MELAS; those being infant or young child and with lesions in basal ganglia, thalamus and brainstem could be LS. Conclusions:Mitochondrial disease caused by m.14453G>A gene mutation shows a great heterogeneity, which can cause MELAS and LS. The clinical phenotype of the m.14453G>A mutation may be related to the age of onset and lesion′ s location.

Objective:To compare the effects of auricular point intradermal needling with auricular point sticking on digestive symptoms and quality of life in patients undergoing platinum-based chemotherapy regimens. Methods:Ninety-six patients receiving platinum-based chemotherapy were randomly assigned to three groups using the random number table method,with 32 cases in each group.The control group received conventional nursing care plus 5-hydroxytryptamine receptor antagonist,and the other two groups received additional auricular point intradermal needling or sticking.For the three groups of participants,the acute and delayed vomiting and nausea severity,quality of life,and the additional antiemetic consumption rate were observed. Results:The three groups had no significant differences in the acute vomiting frequency and nausea severity and appetite(P>0.05)but had significant differences in the delayed vomiting frequency and nausea severity(P<0.05);the auricular point intradermal needling group won over the auricular point sticking group.The three groups showed significant differences in comparing the appetite in the delayed stage(P<0.05);both auricular point intradermal needling and sticking groups showed advantages over the control group(P<0.05),but no significant difference existed between the auricular point intradermal needling and sticking groups(P>0.05).There were significant differences in comparing the functional living index-emesis(FLIE)score in both acute and delayed stages among the three groups(P<0.05)and the result favored the auricular point intradermal needling group over the auricular point sticking group(P<0.05).The additional antiemetic consumption rate was higher in the control group than in the other groups(P<0.05). Conclusion:Based on the conventional nursing and 5-hydroxytryptamine receptor antagonist,adding either auricular point intradermal needling or auricular point sticking can lower the vomiting frequency and nausea severity in the delayed stage and improve appetite in patients receiving platinum-based chemotherapy regimen,but they have no notable impact on digestive symptoms in the acute stage;auricular point intradermal needling is superior to auricular point sticking in comparing the overall efficacy.Both auricular point intradermal needling and auricular point sticking can enhance the quality of life in patients undergoing chemotherapy and reduce their additional antiemetic consumption.

The article analyzes chief physician SUN Wuquan's empirical characteristics in treating neck-type cervical spondylosis:disease differentiation combined with pattern differentiation,emphasizing the assessment of tendons and bones,with DING's Tuina(Chinese therapeutic massage)manipulations and static Gongfa(Qigong exercise)as the predominant treatment,inherits the academic features of DING's Tuina school,"paying equal attention to tendons and bones,putting function first";thus provides a reference for treating neck-type cervical spondylosis with Tuina therapy.