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

Citrus, which has been consumed internationally for a long time, is widely used as a health food. Citrus and its active components exert significant effects on oxidative stress and lipid metabolism, which are closely associated with female reproductive health. Studies suggest that citrus-derived compounds may alleviate oxidative stress by activating signaling pathways such as nuclear factor erythroid 2-related factor 2 (Nrf2) and Sirtuin 1 (SIRT1), and improve lipid metabolism through the activation of pathways such as peroxisome proliferator-activated receptor α (PPARα). This review focuses on the effects of Citrus on oxidative stress and lipid metabolism, aiming to provide new insights for promoting female reproductive health; however, further work is needed to elucidate the mechanisms involved and validate the therapeutic potential of Citrus's bioactive components in clinical settings.
Citrus/chemistry* ; Oxidative Stress/drug effects* ; Female ; Humans ; Lipid Metabolism/drug effects* ; Reproductive Health ; Animals ; Sirtuin 1/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Signal Transduction/drug effects* ; PPAR alpha/metabolism*

Objective:To compare the association between body mass index(BMI)trajectories deter-mined by different methods and the risk of overweight in early childhood in a prospective cohort study,and to identify children with higher risk of obesity during critical growth windows of early childhood.Methods:A total of 1 330 children from Peking University Birth Cohort in Tongzhou(PKUBC-T)were included in this study.The children were followed up at birth,1,3,6,9,12,18,and 24 months and 3 years of age to obtain their height/length and weight data,and calculate BMI Z-score.Latent class growth mixture modeling(GMM)and longitudinal data-based k-means clustering algorithm(KML)were used to determine the grouping of early childhood BMI trajectories from birth to 24 mouths.Linear regres-sion was used to compare the association between early childhood BMI trajectories determined by different methods and BMI Z-score at 3 years of age.The predictive performance of early childhood BMI trajecto-ries determined by different methods in predicting the risk of overweight(BMI Z-score＞1)at 3 years was compared using the average area under the curve(AUC)of 5-fold cross-validation in Logistic regres-sion models.Results:In the study population included in this research,the three-category trajectories determined using GMM were classified as low,medium,and high,accounting for 39.7％,54.1％,and 6.2％of the participants,respectively.The two-category trajectories determined using the KML method were classified as low and high,representing 50.3％and 49.7％of the participants,respectively.The three-category trajectories determined using the KML method were classified as low,medium,and high,accounting for 31.1％,47.4％,and 21.5％of the participants,respectively.There were certain differ-ences in the growth patterns reflected by the early childhood BMI trajectories determined using different methods.Linear regression analysis found that after adjusting for maternal ethnicity,educational level,delivery mode,parity,maternal age at delivery,gestational week at delivery,children's gender,and breastfeeding at 1 month of age,the association between the high trajectory group in the three-category trajectories determined by the KML method(manifested by a slightly higher BMI at birth,followed by rapid growth during infancy and a stable-high BMI until 24 months)and BMI Z-scores at 3 years was the strongest.Logistic regression analysis revealed that the three-category trajectory grouping determined by the KML method had the best predictive performance for the risk of overweight at 3 years.The results were basically consistent after additional adjustment for the high bound score of the child's diet balanced index,average daily physical activity time,and screen time.Conclusion:This study used different methods to identify early childhood BMI trajectories with varying characteristics,and found that the high trajectory group determined by the KML method was better able to identify children with a higher risk of overweight in early childhood.This provides scientific evidence for selecting appropriate methods to de-fine early childhood BMI trajectories.

AIM: To investigate the effects of agkis-trodon halys venom anti-tumor component (AHVAC-) on the biological behavior of gastric cancer MKN-28 cells. METHODS: Gastric cancer MKN-28 cells were treated with the experimental concentrations (5, 10, 15 μg/mL) of AHAVC- for 24 h. Cell proliferation and toxicity assay (cell counting kit-8, CCK-8) was used to detect the inhibition rates of the cells in different concentrations of AHVAC-. The migration ability of the cells was evaluated by wound-healing and Transwell assay. The apoptosis were observed by laser confocal microscopy with annexin V-mCherry/DAPI double staining, and the apoptosis rates were analyzed by flow cytometry with annexin V-FITC/PI double fluorescence staining. The protein level of Caspease-3 was determined by Western blot. RESULTS: Compared with normal control group, the results of AHVAC- concentration groups showed that with the increase of AHVAC- concentration, the proliferative activity of MN-28 cells decreased gradually (P<0.01), the cell migration ability decreased gradually (P<0.01), and the cell apoptosis rate increased (P<0.05). The expression of apoptosis-related protein Caspease-3 was up-regulated (P<0.01). CONCLUSION: AHVAC- inhibits proliferation and migration of gastric cancer MSN-28 cells and induces apoptosis.

Purpose/Significance Gestational hypertension poses a serious threat to maternal health.Artificial intelligence(AI)fol-low-up and management systems contributes to the health of gestational hypertension.Method/Process The paper establishes an AI fol-low-up system for gestational hypertension based on big data technology and data platforms,including modules such as patient informa-tion management,follow-up data management,follow-up plan management,and patient course management.Result/Conclusion The follow-up system can assist doctors in understanding changes in patients'diseases and meet the hospital's follow-up management re-quirements for gestational hypertension in outpatient clinics.

Objective To explore the feasibility and safety of submucosal tunneling endoscopic resection(STER)for the treatment of giant(long diameter≥3.5 cm)symptomatic submucosal tumors(SMT)originating from the esophageal and cardiac muscularis propria layer.Methods A retrospective analysis was conducted on patients with giant symptomatic SMT of the esophagus and cardia treated with STER at the Endoscopy Center of Zhongshan Hospital,Fudan University from January 2017 to January 2020.Clinical characteristics and follow-up data of patients were collected.The efficacy of STER was evaluated by complete resection rate,recurrence rate,and residual rate.The safety of the procedure was assessed by the occurrence of procedure-related complications.Results A total of 111 patients with SMT were included,including 65 males and 46 females,with an average age of(43.2±11.6)years old.Among them,11 patients(9.9％)presented with typical symptoms.Leiomyomas accounted for 105 cases,gastrointestinal stromal tumors for 2 cases,and schwannoma for 4 cases.The median long diameter of the tumors was 5 cm,and the median short diameter was 3 cm.The median operation time was 70 minutes,and the median time of hospital stay was 3 days.The success rate of STER was 100％,with a complete resection rate of 73.9％.Intraoperative mucosal injury was observed in 18 cases(16.2％),postoperative complications occurred in 16 cases(14.4％),including severe pneumothorax/pleural effusion requiring drainage in 10 cases(9.0％),delayed bleeding in 1 case(0.9％),moderate or severe fever in 4 cases(3.6％),and infection in tunnel in 1 case(0.9％).Follow-up at 1-18 months showed no tumor residue,recurrence,esophageal stenosis,diverticula or other long-term complications.Conclusions STER is a safe and effective treatment for giant symptomatic SMT of the esophagus and cardia.

Objective:To construct an explainable artificial intelligence(AI) model of risk characteristics of papillary thyroid carcinoma(PTC), and to explore its value of it combined with clinical features in predicting cervical lymph node metastasis(CLNM) in PTC patients.Methods:From January 2021 to September 2022, 422 patients(422 nodules) with pathologically confirmed PTC underwent thyroidectomy and neck lymph node dissection in the Second Affiliated Hospital of Xi′an Jiaotong University were retrospectively collected, the patients were randomly divided into training set and test set according to the ratio of 7∶3. Ultrasonographic features highly correlated with PTC risk characteristics were extracted by traditional machine learning method, and an intelligent prediction model with optimal probability of risk characteristics was established. Then, a risk model for predicting CLNM of PTC patients was constructed in combination with clinical features. The diagnostic effectiveness of the model was evaluated by drawing a ROC curve and calculating the area under curve (AUC).Results:In the AI explaineable model of PTC risk characteristics in the test set, the intelligent diagnosis model of calcification based on logistic regression classification showed the highest diagnostic efficiency, with an AUC of 0.87 ( P<0.05). Compared with the probability model of risk characteristic of PTC alone, the comprehensive model combined with clinical characteristics showed higher diagnostic efficiency in predicting CLNM of PTC patients, with AUC of 0.97, diagnostic critical value of 0.15, corresponding accuracy, sensitivity and specificity of 92.65%, 92.76% and 92.54%, respectively (all P<0.05). Conclusions:The explaineble risk characteristics of PTC AI model combined with clinical features can effectively predict the cervical lymph node metastasis of PTC, and then provide effective information for clinical decision-making of PTC patients.

Objective:To observe the effects of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor combined with rosuvastatin on lipid levels and short-term prognosis in patients with acute ischemic stroke, and to explore the optimal therapeutic regimen in terms of efficacy and safety, so as to provide a basis for clinical practice.Methods:Consecutive patients with acute cerebral infarction within 72 hours of onset and lipids≥2.6 mmol/L admitted to Xuzhou Central Hospital from April 2022 to March 2023 were included in the study, and the randomized numeric table method was used to divide them into 3 groups of different treatment regimens, group A (rosuvastatin 20 mg, once a day), group B (rosuvastatin 10 mg, once a day+alirocumab 75 mg, once 2 weeks) and group C (rosuvastatin 20 mg, once a day+alirocumab 75 mg, once 2 weeks). General baseline data, National Institutes of Health Stroke Scale score, modified Rankin Scale score on day 90 and the occurrence of adverse events and serious adverse events were collected from the 3 groups. The primary efficacy outcome was the degree of reduction in low density lipoprotein-cholesterol (LDL-C) from baseline on day 90. The secondary efficacy outcomes were recurrence rate and time to recurrence in stroke patients within 90 days,etc. The primary safety outcome was hepatic insufficiency (transaminase elevation≥3 times normal) within 90 days. The secondary safety outcomes were death due to stroke within 90 days and fatal and nonfatal myocardial infarction.Results:A total of 501 patients were included, 166 patients in group A, 167 patients in group B, and 168 patients in group C. The differences in the baseline data of the 3 groups were not statistically significant (all P>0.05). LDL-C was reduced from baseline on day 90 in groups A, B, and C, with the differences of -1.5 (-1.7, -1.4) mmol/L, -2.2 (-2.5, -2.1) mmol/L and -2.2 (-2.6, -2.1) mmol/L, respectively, with statistically significant differences among the 3 groups ( H=1.497, P<0.001); the differences between the group A and group B, and between the group A and group C, were statistically significant ( Z=-11.125, P=0.006; Z=-9.475, P=0.012), while the difference between the group B and group C was not statistically significant ( Z=1.650, P=0.946). The numbers of 90-day stroke recurrence cases (recurrence rate) in patients in the groups A, B, and C were 12 (7.2%), 4 (2.4%), and 5 (3.0%), respectively, without statistically significant difference among the 3 groups ( χ 2=5.773, P>0.05); the recurrence time of patients in the groups A, B and C was (43.0±7.4) d, (66.0±8.3) d and (62.2±5.6) d, respectively, and the differences among the 3 groups were statistically significant ( F=14.096, P=0.001). Compared with the group A, patients in the groups B and C had a prolonged time to stroke recurrence within 90 days ( Z=-3.108, P=0.002; Z=-2.871, P=0.004), whereas the difference in the time to stroke recurrence within 90 days between patients in the groups B and C was not statistically significant ( Z=0.397, P=0.692). The time to stroke recurrence within 90 days was positively correlated with the level of LDL-C on day 90 ( β=0.850, P=0.031). Ten patients (6.0%) in the group A developed hepatic insufficiency, 1 patient (0.6%) in the group B, and 9 patients (5.4%) in the group C. The differences among the 3 groups were statistically significant (χ 2=7.622, P=0.022); and the difference between the group B and group C was statistically significant ( P=0.011). The differences of secondary safety endpoints, death due to stroke within 90 days [1 case (0.6%) in the group A, 0 case (0) in the group B, and 1 case (0.6%) in the group C], fatal and nonfatal myocardial infarction within 90 days [3 cases (1.8%) in the group A, 1 case (0.6%) in the group B, and 1 case (0.6%) in the group C], were not statistically significant among the 3 groups (all P>0.05). Conclusions:In patients with acute ischemic stroke, PCSK9 inhibitor combined with rosuvastatin (both medium and high doses) significantly reduced LDL-C levels compared with baseline, and at the same time prolonged the time to stroke recurrence, reduced adverse effects such as hepatic insufficiency, and had a high degree of safety. PCSK9 inhibitor combined with medium-dose rosuvastatin had a better effect.

Objective:To analyze the clinical features of gastritis cystica profunda (GCP) and investigate the risk factors associated with its coexistence with gastric cancer.Methods:Data of 149 patients with pathologically confirmed GCP at Zhongshan Hospital of Fudan University between January 2015 and March 2022 were retrospectively analyzed for basic information, clinical data, lesion manifestations and pathological results, of which 106 were pathologically confirmed GCP after endoscopic resection and 43 others were pathologically confirmed GCP after surgical procedures. Among 149 patients, 56 were in the simple GCP group, and 93 in the GCP combined with gastric cancer group.Results:In the simple GCP group of 56 patients, 62.5% (35/56) were male and the mean age was 58.8 years. The predominant site of involvement was in the upper gastric segment (cardia and fundus) (51.8%,29/56), with manifestations primarily of the polypoid bulge type (41.1%,23/56) and submucosal bulge type (35.7%,20/56). Clinical symptoms were mostly atypical. In the group where GCP was combined with gastric cancer (93 cases), males accounted for 90.3% (84/93), the median age was 66.9 years, the upper gastric segment was predominantly affected (75.3%, 70/93), with differentiated cancer being the most common histological type (91.4%, 85/93). For 76 cases of early gastric cancer combined with GCP, mucosal lesions were the main presentation (73.7%, 56/76) with atypical clinical symptoms. Furthermore, in 17 cases of progressive gastric cancer combined with GCP, the manifestations were mainly bulging ulcers (88.2%, 15/17), and most of them were referred to the doctor because of abdominal pain and black stools (100.0%, 17/17). Binary logistic regression analysis showed that being male ( P=0.004, OR=4.411, 95% CI: 1.621-12.002), age ( P=0.001, OR=1.085, 95% CI: 1.036-1.136) and endoscopic manifestations of mucosal lesions ( P<0.001, OR=5.080, 95% CI: 2.162-11.939) were risk factors for GCP combined with gastric cancer, but involvement of the upper gastric segment was not related to combination with gastric cancer ( P=0.430, OR=0.707, 95% CI: 0.299-1.672). Among 106 patients with endoscopic resection, 57 cases of early gastric cancer combined with GCP had a median lesion length of 2.50 cm; 49 cases of GCP alone had a median lesion length of 1.20 cm, with significant difference ( Z=-5.503, P<0.001). All upper gastric GCP combined with early gastric cancer in endoscopically treated patients were cancers of the cardia, most of which were superficial elevation with the concave type (0-Ⅱa+Ⅱc) (44.7%, 21/47). 75.4% (43/57) patients with gastric cancer combined with GCP were graded as curative resection (eCuraA) after endoscopic surgery , and none of those who had additional surgery after endoscopic surgery had lymph node metastasis. There were 8 cases with history of gastric surgery, 7 of esophageal cancer, and 10 of multiple neoplastic gastric lesions in the 149 patients with GCP. Conclusion:GCP often occurs in the upper gastric region and is not inherently associated with the presence of gastric cancer. However, when coexisting with gastric cancer, it tends to affect elderly men, present with mucosal lesions of a differentiated histological type, and may be accompanied by esophageal or other gastric cancers. Notably, GCP is frequently identified as para-cancerous lesion, and endoscopic treatment emerges as a safe and effective approach, characterized by a high rate of curative endoscopic resections and a low incidence of lymphatic metastases.