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

This study investigates the expression pattern and functional significance of EF-hand domain-containing protein 2 (EFHD2) in hepatocellular carcinoma (HCC), with particular focus on its regulatory effects on tumor proliferation, migration, and invasion. Cellular experimental study was completed from June 2024 to January 2025 in the Basic Laboratory of the General Hospital of Southern Theater Command. TCGA database to determine EFHD2 expression and its clinicopathological correlations. GSCA database to assess methylation patterns and immune infiltration. Model of transient overexpression and knockdown of EFHD2 was constructed in hepatocellular carcinoma cells Hep3B, then RT-qPCR and Western blot were applied to verify the transfection efficiency. CCK-8 and colony formation assays for proliferation assessment, Transwell chambers for migration/invasion quantification. Protein-protein interaction networks were constructed via STRING, followed by GO/KEGG enrichment analysis. Statistical analysis was performed using the two independent samples t-test. The results showed that EFHD2 demonstrated significant upregulation in HCC tissues versus normal controls ( P<0.05). Elevated EFHD2 expression correlated with advanced clinical stage ( P<0.05) and poor differentiation ( P<0.05). In the CCK-8 assay, the EFHD2 overexpression group demonstrated significantly higher cell viability than the control group, as evidenced by 450 nm relative absorbance values on Day 1 (0.529±0.019 vs. 0.515±0.016, F=0.041, P=0.320), Day 2 (1.356±0.019 vs. 1.094±0.042, F=3.833, P<0.001), Day 3 (2.817±0.049 vs. 2.143±0.124, F=3.833, P<0.001), and Day 4 (3.848±0.015 vs. 3.430±0.021, F=0.469, P<0.001). The EFHD2 knockdown group showed reduced cell viability compared to controls: Day 1 (0.541±0.020 vs. 0.552±0.015, F=0.098, P=0.423), Day 2 (1.154±0.009 vs. 1.326±0.029, F=2.485, P<0.001), Day 3 (2.453±0.041 vs. 2.653±0.031, F=0.479, P<0.001), and Day 4 (3.685±0.038 vs. 3.836±0.021, F=6.804, P<0.001). In colony formation assays, the overexpression group displayed a significant increase in colony numbers (254.667±23.861 vs. 186.000±16.703, F=0.865, P=0.015), whereas the knockdown group exhibited decreased colony formation (229.000±24.637 vs. 306.667±36.501, F=0.988, P=0.038). In Transwell assays, the EFHD2 overexpression group revealed enhanced migratory capacity [ (605.000±72.670) cells vs. (472.667±28.095) cells, F=2.462, P=0.042] and invasive potential [(767.333±21.221) cells vs. (414.333±16.623) cells, F=0.331, P<0.001]. The knockdown group showed attenuated migration [(311.000±71.084) cells vs. (479.667±50.846) cells, F=0.718, P=0.029] and invasion [(247.667±48.263) cells vs. (345.667±32.130) cells, F=0.727, P=0.043] compared to controls. The network of EFHD2-interacting proteins was further constructed by the STRING database, and the GO and KEGG analysis were used to perform bioinformatics analysis reveal that EFHD2 is mainly involved in actin cytoskeleton regulation. In conclusion, EFHD2 is highly expressed in HCC and is involved in the process of proliferation, migration and invasion of HCC.

This study investigates the expression pattern and functional significance of EF-hand domain-containing protein 2 (EFHD2) in hepatocellular carcinoma (HCC), with particular focus on its regulatory effects on tumor proliferation, migration, and invasion. Cellular experimental study was completed from June 2024 to January 2025 in the Basic Laboratory of the General Hospital of Southern Theater Command. TCGA database to determine EFHD2 expression and its clinicopathological correlations. GSCA database to assess methylation patterns and immune infiltration. Model of transient overexpression and knockdown of EFHD2 was constructed in hepatocellular carcinoma cells Hep3B, then RT-qPCR and Western blot were applied to verify the transfection efficiency. CCK-8 and colony formation assays for proliferation assessment, Transwell chambers for migration/invasion quantification. Protein-protein interaction networks were constructed via STRING, followed by GO/KEGG enrichment analysis. Statistical analysis was performed using the two independent samples t-test. The results showed that EFHD2 demonstrated significant upregulation in HCC tissues versus normal controls ( P<0.05). Elevated EFHD2 expression correlated with advanced clinical stage ( P<0.05) and poor differentiation ( P<0.05). In the CCK-8 assay, the EFHD2 overexpression group demonstrated significantly higher cell viability than the control group, as evidenced by 450 nm relative absorbance values on Day 1 (0.529±0.019 vs. 0.515±0.016, F=0.041, P=0.320), Day 2 (1.356±0.019 vs. 1.094±0.042, F=3.833, P<0.001), Day 3 (2.817±0.049 vs. 2.143±0.124, F=3.833, P<0.001), and Day 4 (3.848±0.015 vs. 3.430±0.021, F=0.469, P<0.001). The EFHD2 knockdown group showed reduced cell viability compared to controls: Day 1 (0.541±0.020 vs. 0.552±0.015, F=0.098, P=0.423), Day 2 (1.154±0.009 vs. 1.326±0.029, F=2.485, P<0.001), Day 3 (2.453±0.041 vs. 2.653±0.031, F=0.479, P<0.001), and Day 4 (3.685±0.038 vs. 3.836±0.021, F=6.804, P<0.001). In colony formation assays, the overexpression group displayed a significant increase in colony numbers (254.667±23.861 vs. 186.000±16.703, F=0.865, P=0.015), whereas the knockdown group exhibited decreased colony formation (229.000±24.637 vs. 306.667±36.501, F=0.988, P=0.038). In Transwell assays, the EFHD2 overexpression group revealed enhanced migratory capacity [ (605.000±72.670) cells vs. (472.667±28.095) cells, F=2.462, P=0.042] and invasive potential [(767.333±21.221) cells vs. (414.333±16.623) cells, F=0.331, P<0.001]. The knockdown group showed attenuated migration [(311.000±71.084) cells vs. (479.667±50.846) cells, F=0.718, P=0.029] and invasion [(247.667±48.263) cells vs. (345.667±32.130) cells, F=0.727, P=0.043] compared to controls. The network of EFHD2-interacting proteins was further constructed by the STRING database, and the GO and KEGG analysis were used to perform bioinformatics analysis reveal that EFHD2 is mainly involved in actin cytoskeleton regulation. In conclusion, EFHD2 is highly expressed in HCC and is involved in the process of proliferation, migration and invasion of HCC.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective:To investigate the therapeutic effect of Flow-through anterolateral thigh perforator flap (ALTPF) or medial sural artery perforator flap (MSAPF) in repair of Gustilo III C wound of foot.Methods:From July 2015 to June 2021, 8 patients with Gustilo III C wound of foot were treated in the Department of Foot and Ankle Surgery of Wuxi No.9 People’s Hospital. The patients were 7 males and 1 female, aged 25-62 years old, and (45.88±12.96) years old in average. Flow-through ALTPF or Flow-through MSAPF were used to repair the defect according to the size of the wound and the length and diameter of the defect vascular. Among the patients, 6 were repaired with free Flow-through ALTPF, and 2 with free Flow-through MSAPF. The size of flap was 9 cm×5 cm-22 cm×8 cm with (115.00±46.16) cm 2 in average, and the vascular bridging was 6-12 cm in length, with (8.75±2.50) cm in average. All patients received outpatient follow-up. The appearance of the flap, blood supply of affected limb, healing of fracture and dislocation and the recovery of limb function were recorded. Maryland score was used to evaluate functional recovery. Results:The flaps survived uneventfully in all 8 patients, and the wounds in donor site healed primarily. All patients were followed-up for 6-22 months with (12.25±5.39 ) months in average. At the last follow-up, all the flaps had satisfactory contour in soft texture and blood supply without occlusion in the bridging vessels. The fractures and dislocation were healed, and the appearance and function of the foot recovered satisfactorily. The Maryland score showed excellent in 3 patients, good in 4 patients and fair in 1 patient.Conclusion:Flow-through ALTPF or MSAPF can selectively used to reconstruct the Gustilo III C wound of foot in one stage. The functional recovery of the affected limb was satisfactory and the clinical effect was good.

Objective:To evaluate the deformity changes in the treatment of congenital clubfoot in infants by ultrasound, and to explore its clinical application value.Methods:Seventeen infants with congenital clubfoot treated in the Department of Pediatric Orthopaedics of the Third Affiliated Hospital of Zhengzhou University from March 2020 to June 2021 and 27 normal infants in the same period were selected. The distance between medial malleolus and scaphoids (MM-N distance) of all feet was measured by ultrasound. The distance from the tangent line of the lateral edge of calcaneus to the midpoint of the lateral edge of the chondroid bone (C-C distance), medial soft tissue thickness and tibial calcaneal angle were measured by ultrasound. The data before, after treatment and during follow-up were statistically analyzed.Results:A total of 88 feet of 44 infants were evaluated. The mean number of cast was 4.7±1.1, the follow-up time was (96.9±59.3)days. The MM-N distance, C-C distance and posterior tibial calcaneal angle in the clubfoot group were improved after treatment and at the last follow-up, and the differences were statistically significant (all P<0.01). During the treatment, 1 case had false correction, and 2 cases recurred in the last follow-up. Conclusions:Ultrasound can clearly display the medial, dorsal, lateral and posterior articular structures of normal and clubfoot, and can observe the deformity changes of clubfoot during the correction process, which can provide guidance for the clinical treatment of clubfoot.

Objective:To analyze the predictive value of enhanced MRI in the outcome of prolapsed and sequestrated lumbar disc herniation through a retrospective analysis.Methods:A retrospective analysis of the data of 64 patients with prolapsed and sequestrated lumbar disc herniation from January 2015 to December 2018, including 38 males and 26 females; age 35.72±12.44 years (range, 22-64 years) ; 43 cases of prolapsed type, 21 cases of sequestrated type. Conservative treatment was the first choice for all patients, in case of surgical indications during the treatment, percutaneous endoscopic lumbar discectomy or fenestration discectomy will be performed. Enhanced MRI was performed at the first and last inspections, the volume of the protrusion, the thickness of rim enhancement (Tr), and the extent of rim enhancement (Er) were measured and calculated at the same time. According to the ring around the protrusion, the size of the rim-enhancement area was divided into type I-III; then compared the relationship between the rim-enhancement signal differentiation and the resorption rate of protrusions, and the correlation between Tr, Er values and the resorption rate of protrusions during the initial inspection.Results:Among the 64 patients, 42 patients completed conservative treatment, and 22 received surgical treatment. According to the rim-enhancement signal differentiation, 23 cases were treated conservatively for type I, 3 cases were treated by surgery; 16 cases were treated for type II conservatively, 7 cases were treated by surgery; 3 cases were treated for type III conservatively, and 12 cases were treated by surgery. All patients were followed up for 12 to 34 months. Among 42 conservatively treated patients, The volume of the protrusion before treatment was 2 645.67±690.86 mm 3, and the volume of the protrusion after treatment was 842.76±573.35 mm 3. The volume of protrusions before and after treatment was statistical significance ( t=11.897, P<0.001), Tr was 1.38±0.83 mm, and Er was 73.08%±34.39%, the resorption rate of protrusions was 65.10%±24.50%, and 39 cases (92.86%, 39/42) reached the standard for protrusion resorption (resorption rate ≥30%); 23 cases of type I , the resorption rate was 76.54%±18.62%; 16 cases of type II had an resorption rate of 56.81%±21.44%; 3 cases of type III had an resorption rate of 21.58%±12.19%. The resorption rate of type III were compared by single factor analysis of variance, and the difference was statistically significant ( F=12.885, P<0.001); 32 cases of both type I and II (82.05%, 32/39) had significant resorption (resorption rate ≥50%), and no case of type Ⅲ had significant resorption, comparing with type I and II, the difference was statistically significant ( P=0.010); Tr was positively correlated with resorption rate ( r=0.569, P<0.001), Er was positively correlated with resorption rate ( r=0.677, P<0.001). Conclusion:Under close clinical observation, parts of the prolapsed or sequestrated lumbar disc herniations can be conservatively treated, and the herniated disc can be resorption in many people and the clinical symptoms were alleviated. Rim-enhancement signal differentiation by enhanced MR has a better predictive value for the outcome of the herniation, type I is more prone to resorption, preferred conservative treatment, type Ⅲ is not easy to resorption, preferred surgery treatment, and the higher thickness of rim enhancement, the greater extend the rim-enhancement, the more prone to resorption phenomenon.

Objective To explore the effect of angiogenesis in carotid atherosclerotic plaque.Methods From Jan 2016 to Aug 2016,Carotid artery plaque was abtained in 52 cases after carotid endarterectomy at the Department of Cardiovascular Surgery of China-Japan Friendship Hospital.Patients were divided into symptomatic group and asymptomatic group.Specimens were stained with HE and Movat,and the density,size,distribution and morphology of neovascularization were counted.Results The density of neovascularization in the symptomatic group and the asymptomatic group were 5.27 ± 0.46 and 2.30 ±0.29,respectively (P ＜ 0.001),the average cross-sectional area of neovascularization in the symptomatic group was (2.26±0.21) mm2 and (1.00 ±0.48) mm2 in the asymptomatic group (P=0.02).In the distribution,the symptomatic group and the asymptomatic group were 3.37 ± 0.46/ mm2,1.32 ±0.16/mm2 in basal part,3.71 ±0.42/mm2,1.56 ±0.20/mm2 in the shoulder part,3.48 ±0.44/mm2,1.55 ± 0.21/ mm2 in the fibrous cap,respectively (P ＜ 0.001).Conclusion The density and cross-sectional area of neovascularization in the symptomatic group were larger than those in the asymptomatic group,irregular branching vessels were dominant.

Objective To investigate the value of high frequency magnetoencephalography signals in the localization of refractory temporal lobe epilepsy. Methods Retrospective analysis was performed in 10 patients with refractory temporal lobe epilepsy admitted to and accepted surgery in our hospital from January 2015 to December 2015. Surgical approaches of these patients were determined according to the results of long-term video EEG monitoring (VEEG), MR imaging, and conventional and high-frequency magnetoencephalography (MEG). MEG positioning analysis was performed after the surgery; followed up for 12 months was performed to evaluate the surgical efficacies. Results The surgery was effective in all the 10 patients; 5 patients achieved Engel grading Ⅰ, 2 patients achieved Engel grading Ⅱ, and 3 patients achieved Engel grading Ⅲ. The results of high-frequency MEG analysis indicated that 8 lesions were consistent with the surgical sites, enjoying good results; while the positioning error of the 2 patients was large. Conclusions The localization analysis of high-frequency neuromagnetic signals has the potential to determine epileptogenic zones preoperatively for epilepsy surgery. High-frequency oscillation is a new biomarker for the diagnosis of epilepsy.

BACKGROUND:Flexible intramedulary nailing and external fixation for pediatric femoral shaft fractures are two common methods in the clinic. It remains controversial which fixation methods are better. OBJECTIVE:To systematicaly evaluate the therapeutic effects of flexible intramedulary nailing and external fixation for pediatric femoral shaft fractures. METHODS: A computer-based search was performed on PubMed, Embase, Medline, and Cochrane library for literatures on clinical controled trials of flexible intramedulary nailing and external fixation for pediatric femoral shaft fractures published before November 25, 2014. Literature language was not limited. The age of subjects was from 3 to 15 years. Modified Jadad was utilized to assess methodological quality of the included studies. Meta-analysis was carried out using Stata 12.0 software. RESULTS AND CONCLUSION:Six papers involving 237 patients were included. Meta-analysis results showed that compared with external fixation, a low incidence of overal complications [relative risk (RR)=0.30, 95% confidence interval (CI): 0.19-0.46;P < 0.001] and pin-hole infection (RR=0.286, 95%CI: 0.13-0.61;P= 0.001), but a high risk of needle tail irritation (RR=1.86, 95%CI: 1.35-2.56;P < 0.001) were found folowing flexible intramedulary nailing. No significant differences in other complications were found between the two groups. These results confirm that compared with external fixation, elastic intramedulary nail has fewer complications and faster fracture healing. Elastic intramedulary nail is recommended for single pediatric femoral shaft fractures. However, external fixation is a better option for high energy injury of lower limbs, multiple trauma or severely soft tissue injury.