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 investigate the effectiveness of posterior minimally invasive approach in the treatment of posterior wall acetabular fractures. METHODS: The clinical data of 17 patients with posterior wall acetabular fractures treated with posterior minimally invasive approach between March 2019 and June 2023 were retrospectively analyzed. There were 14 males and 3 females with an average age of 41 years ranging from 28 to 57 years. The causes of injury were traffic accident in 12 cases and falling from height in 5 cases. There were 3 cases complicated with posterior hip dislocation and 2 cases complicated with sciatic nerve injury. According to AO/Orthopaedic Trauma Association (AO/OTA) classification, there were 11 cases of type A1.1 and 6 cases of type A1.2. The time from injury to operation was 5-8 days, with an average of 6.2 days. The incision length, intraoperative blood loss, and operation time were recorded. The quality of posterior wall fracture reduction were evaluated by Matta criteria, and hip function were evaluated by modified Merle d'Aubign-Postel score criteria at 6 months after operation and last follow-up. RESULTS: The operation was successfully completed in 17 cases. The length of incision ranged from 7 to 9 cm, with an average of 8.3 cm, and all incisions healed by first intention. The intraoperative blood loss ranged from 200 to 350 mL, with an average of 281 mL. The operation time ranged from 45 to 70 minutes, with an average of 57 minutes. Two patients had sciatic nerve injury before operation, and the sciatic nerve function recovered completely at 3 months after operation; the other 15 patients had no symptoms of sciatic nerve injury after operation. All the 17 patients were followed up 14-27 months, with an average of 19.5 months. At 1 week after operation, according to the Matta criteria, anatomical reduction was achieved in 12 cases and satisfactory reduction in 5 cases, with a satisfaction rate of 100%. According to the modified Merle d'Aubign-Postel scoring system, the hip function score was 13-18 (mean, 16.1) at 6 months after operation. Among them, 5 cases were excellent, 9 were good, and 3 were fair, with an excellent and good rate of 82.4%. At last follow-up, the hip function score was 7-18 (mean, 13.7), of which 3 cases were excellent, 9 were good, 3 were fair, and 2 were poor, with an excellent and good rate of 70.6%. During the follow-up, there was no infection, failure of internal fixation, and femoral head necrosis, and heterotopic ossification occurred in 2 cases. CONCLUSION The posterior minimally invasive approach has the advantages of less trauma, shorter operation time, less blood loss, without cutting off the external rotator muscle. Exposure through the gluteus medius-piriformis space and piriformis-supercilium space can provide sufficient safe exposure for the posterior wall acetabulum fracture, which is a reliable alternative approach for the posterior acetabular fracture.
Humans ; Acetabulum/surgery* ; Male ; Female ; Adult ; Middle Aged ; Minimally Invasive Surgical Procedures/methods* ; Retrospective Studies ; Fracture Fixation, Internal/instrumentation* ; Fractures, Bone/diagnostic imaging* ; Treatment Outcome ; Operative Time

OBJECTIVE: To explore the effectiveness of additional anti-rotation steel plate assisted intramedullary nail technology in treatment of aseptic femoral non-union patients. METHODS: A retrospective analysis was conducted on 21 patients with aseptic femoral non-union who admitted between September 2020 and October 2024 and treated with additional anti-rotation steel plate assisted intramedullary nail technology. There were 17 males and 4 females, aged 25-67 years (mean, 44 years). There were 19 cases of femoral anterograde intramedullary nail fixation, 1 case of femoral retrograde intramedullary nail fixation, and 1 case of steel plate fixation with fatigue fracture. There were 9 cases of hypertrophic non-union and 12 cases of atrophic non-union. All patients had varying degrees of fracture end atrophy/sclerosis. Among them, 20 patients who were fixed with intramedullary nails underwent removal of soft tissue and hardened bone at the fracture end, and cortical treatment resulted in the appearance of "chili sign" at the fracture end. Iliac bone grafting and anti-rotation steel plate fixation were performed. One patient with steel plate fixation was removed the steel palte and fixed with a retrograde intramedullary nail, while the hardened bone at the fracture end was removed, iliac bone grafting and anti-rotation steel plate fixation were performed. Postoperative follow-up observation included the incision healing, maximum knee flexion range of motion, bone healing, length of lower limbs, and subjective satisfaction. The lower extremity functional scale (LEFS) score was used to evaluate the lower limb function. RESULTS: All incisions healed by first intention. All patients were followed up 7-26 months (mean, 15.5 months). At last follow-up, the femoral fracture healed with the obvious callus formation at the fracture end; the maximum knee flexion range of motion was 95°-127° (mean, 112.67°). The LEFS score increased from 29.9±6.7 before operation to 75.9±3.0 at last follow-up, and the difference was significant (t=-29.622, P<0.001). Except for 1 patient who underwent intramedullary nail dynamic treatment before operation and had a lower limb shortening of about 0.9 cm, the other patients had bilateral lower limbs of equal length. All patients had no postoperative infections, mal-union of fractures, deep vein thrombosis, joint stiffness, or other complications. CONCLUSION The use of additional anti-rotation steel plate assisted intramedullary nail technology in the treatment of aseptic femoral non-union not only overcomes the drawbacks of insufficient stability at the fracture end of intramedullary nails, but also overcomes the shortcomings of biased fixation with steel plates. It has the advantages of minimal trauma, effective maintenance of fracture stability, and ideal postoperative functional recovery, making it an effective treatment for aseptic femoral non-union.
Humans ; Male ; Fracture Fixation, Intramedullary/instrumentation* ; Female ; Bone Plates ; Middle Aged ; Adult ; Femoral Fractures/surgery* ; Retrospective Studies ; Bone Nails ; Aged ; Fractures, Ununited/surgery* ; Treatment Outcome ; Bone Transplantation/methods* ; Steel ; Fracture Healing

OBJECTIVE: To explore prevalence, incidence and possible factors of immediate herniated discs after posterior cervical expansive open-door laminoplasty (EODL). METHODS: Totally 29 patients with cervical spinal stenosis and intervertebral disc herniation who underwent EODL from October 2020 to December 2021 were collected, including 24 males and 5 females, aged from 43 to 81 years old with an average of (61.3±9.0) years old;the courses of disease ranged from 1 to 120 months with an average of (36.4±37.0) months. Three or more intervertebral discs on C₃-C₇ were observed. The clinical efficacy was evaluated according to Japanese Orthopaedic Association (JOA) score before operation, 3 days and 1, 3, 6 and 12 months after operation, respectively. The changes of herniated disc before and after operation were measured by multipoint area method and two-dimensional distance method, and incidence and percentage of herniated disc regression were further calculated. Cervical imaging parameters such as Cobb angle (C₃-C₇), intervertebral angle, T₁ slope (T₁S), spinal canal sagittal diameter, K-line angle, dural sac sagittal diameter were measured and compared before and after operation. Pearson correlation was used to analyze correlation between cervical sagittal imaging parameters and disc herniation changes before and after operation. RESULTS: All patients obtained grade A wound healing, and 14 of them were followed up for 3(1.00, 5.25) months. There were no immediate or long-term postoperative complications. Totally 101 herniated intervertebral discs were measured, of which 79 regression numbers were obtained by area measurement. The number of intervertebral disc regressions by distance measurement was 77. There was no statistically significant difference in Cobb angle, intervertebral angle, T₁S and K-line angle of C₃-C₇ (P>0.05), however, there were statistically significant differences in sagittal diameter of spinal canal, sagittal diameter of dural sac, and JOA score before and after operation(P<0.05). The regression ratio of disc herniation ranged from 5% to 50%, and regression ratio of disc herniation was greater than 25% in 45.57%(36/79). Disc herniation in C_4,5 was positively correlated with sagittal plane diameter in C₅(r=0.423, P=0.028). There was a negative correlation between changes of C_3,4 and C_3,4 intervertebral angle (r=-0.450, P=0.041). The improvement rate of cervical JOA score immediately after operation was (59.54±15.07) %, and postoperative follow-up improved to (76.57±14.66) %. CONCLUSION Herniated disc regression immediately after EODL is a common occurrence, and EODL should be selected as far as possible under the premise of satisfying surgical indications. The regression of disc herniation is positively correlated with spinal canal sagittal diameter, and spinal canal should be enlarged as far as possible in the appropriate scope during EODL, so as to create more opportunities and conditions for disc regression and achieve better clinical results.
Humans ; Female ; Male ; Intervertebral Disc Displacement/diagnostic imaging* ; Spinal Stenosis/diagnostic imaging* ; Laminoplasty/methods* ; Middle Aged ; Aged ; Cervical Vertebrae/diagnostic imaging* ; Adult ; Aged, 80 and over ; Intervertebral Disc/surgery*

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

OBJECTIVE: To investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development. METHODS: A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected. RESULTS: Elevated alanine aminotransferase (ALT) rates in Group C during early, middle, and late pregnancy were 59.87%, 43.95%, and 42.04%, respectively-significantly higher than Groups B (26.45%, 15.70%, 10.74%) and A (23.94%, 19.01%, 6.34%) ( P < 0.05). Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages ( P < 0.05). No significant differences were found in neonatal malformation rates across groups ( P > 0.05). However, neonatal jaundice incidence was significantly greater in Group C (75.16%) compared to Groups A (42.25%) and B (57.02%) ( χ ² = 33.552, P < 0.001). HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice ( OR = 2.111, 95% CI 1.242-3.588, P = 0.006). CONCLUSIONS Chronic HCV infection can affect the liver function of pregnant women, but does not increase the pregnancy or delivery complication risks. HCV RNA(+) is an independent risk factor for neonatal jaundice.
Humans ; Female ; Pregnancy ; Adult ; Pregnancy Complications, Infectious/epidemiology* ; Retrospective Studies ; Pregnancy Outcome ; Infant, Newborn ; Viremia/virology* ; Hepatitis C ; Hepacivirus/physiology* ; Hepatitis C, Chronic/virology* ; Young Adult ; Alanine Transaminase/blood*

This study used kidney metabolomics to investigate the underlying mechanisms of Guilingji (GLJ) on mild cognitive impairment (MCI) rats. The rats were randomly divided into 6 groups (n = 8), i.e., control group, model group, positive drug (Ginkgo biloba tablet, donepezil) group, GLJ group (low and high dose group). The MCI rat model was replicated using subcutaneous injection of D-galactose into the back of the neck along with a semi-high-fat diet for a total of 8 weeks, and drug was administered from the 5th week for 4 weeks. The kidney function and renal pathological changes of each group of rats were tested. And LC-MS based kidney metabolomics coupled with multivariate data analysis were conducted to explore the potential biomarkers, and corresponding metabolic pathways were then determined. After administration of GLJ, the level of urea nitrogen was decreased compared with those of the model group, and the abnormalities of morphology in kidney tissues were improved. The positive drugs (ginkgo biloba tablet and donepezil) had no significant modulating effect on renal function indexes. Ginkgo biloba tablet can lessen the pathological injury of kidney tissue, and donepezil had no improvement on renal histopathology. A total of 23 MCI related differential metabolites were identified in kidney, and 17 metabolites were signifcantly restored by GLJ compared with those of the model group. Additionally, we found that the cysteine and methionine metabolism, nicotinate and nicotinamide metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism were significantly involved in the regulatory effect of GLJ. The results illuminate the "cong shen zhi nao" mechanism of GLJ, and also provide a research basis for the clinical use of GLJ for the treatment of MCI. The animal experiment of this study was approved by the Ethics Committee of Shanxi University (approval number: 2020DW121).

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.