OBJECTIVES: To explore the molecular mechanism of Jiangzhi Huaban Decoction (JZHBD) for improving atherosclerosis through the "qi meridian-blood channels" pathway. METHODS: ApoE^-/- mouse models of atherosclerosis were established by high-fat diet feeding for 8 weeks, with C57BL/6 mice on a normal diet as the controls. Forty ApoE^-/- mouse models were randomized into model group, low-, medium-, and high-dose JZHBD treatment groups, and atorvastatin treatment group (n=8) for their respective treatments for 8 weeks. The changes in body weight and overall condition of the mice were monitored weekly. After the treatments, serum levels of TC, TG, HDL-C, LDL-C, TBA, ALT, and AST of the mice were measured, pathological changes in the liver and aortic root plaques were examined with HE staining, and lipid accumulation in the liver and aortic wall was assessed using Oil Red O staining. The core molecular mechanism was studied through transcriptomics, and the expressions of the key pathway proteins were confirmed using Western blotting and immunohistochemistry. RESULTS: Treatment with JZHBD significantly reduced blood lipid and total bile acid levels, improved liver function and hepatic steatosis, and decreased aortic lipid deposition and plaque area in the mouse models of atherosclerosis. Transcriptomic analysis suggested that the therapeutic mechanism of JZHBD involved reverse cholesterol transport, PPAR signaling, and the inflammatory pathways. In atherosclerotic mice, JZHBD treatment obviously up-regulated hepatic expressions of PPARγ, LXRα, ABCA1, ABCG1, and CYP7A1, down-regulated hepatic expressions of p-p65/p65, IL-6, IL1β in the liver, increased ABCG5 and ABCG8 expressions in the intestines, and decreased ICAM-1 and VCAM-1 expressions in the aortic plaques. CONCLUSIONS JZHBD improves atherosclerotic vascular damage and plaque formation possibly by regulating hepatic reverse cholesterol transport and inflammation via modulating the hepatic PPARγ/LXRα/NF-κB signaling pathway.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Inbred C57BL ; Plaque, Atherosclerotic/metabolism* ; Liver/metabolism* ; Mice ; Atherosclerosis/metabolism* ; Cholesterol/metabolism* ; PPAR gamma/metabolism* ; Male ; Diet, High-Fat ; Biological Transport

Objective To investigate the biomechanical characteristics of the mandibular anterior teeth intrusion assisted by buccal mini-implants,so as to provide theoretical guidance for the clinical treatment of deep overbite and other conditions requiring intrusion of the mandibular anterior teeth.Methods A finite element model of implant screws,clear aligners(CAs)and mandibular complex including the mandibular dentition,periodontal ligament(PDL)and alveolar bone was constructed.The model was designed with 0.2 mm intrusion in the mandibular anterior teeth.Seven groups were set:without traction,30 g,50 g,100 g,150 g,200 g,and 250 g force groups.The stress and displacement of the teeth as well as the related stress distributions of PDL and CAs in each group after loading were analyzed.Results Without traction and under different traction forces,the mandibular anterior teeth tended to be tipped and intruded.With the increase of traction force,the increasing trend was manifested in the vertical displacement and labial displacement of the mandibular anterior teeth.When the traction force reached 200 g,the vertical displacement showed a significant increase,the subsequent increase then showed a tendency to flatten.The ratio of the labial tipping displacement to the intrusive displacement of the mandibular anterior teeth showed a decreasing trend with the increase of traction force.Within a reasonable force range,increasing traction force led to greater bodily intrusion of the anterior teeth.When the traction force was less than 150 g,the mandibular posterior teeth exhibited a tendency of extrusion.When the traction force of more than 150 g was applied,it showed a tendency of intrusion.The PDL stress was concentrated on the labial and cervical surface of the anterior teeth.Conclusions Intrusion efficiency of the mandibular anterior teeth has been effectively improved with CAs assisted by buccal mini-implants.Moreover,the traction force of the mini-implants has a significant impact on the movement of the mandibular anterior teeth.Based on a comprehensive analysis of factors such as the displacement trend of the mandibular dentition and the PDL stress,the optimal force value for buccal traction of the mini-implants to intrude the mandibular anterior teeth can be selected as 150-200 g force.

Objective:To investigate the effects of a low-energy balanced diet combined with exercise intervention on glycolipid metabolism levels in children with simple obesity.Methods:A prospective randomized controlled trial was performed in this study. Forty children with simple obesity who attended the pediatric outpatient department of Tangshan Maternal and Child Health Care Hospital in Hebei Province from January 2022 to January 2024 were selected and randomly divided into two groups using a random number table: an observation group ( n=22) and a control group ( n=18). No weight-loss products were used by any children in either group. The control group received exercise intervention alone, while the observation group received a combined intervention of exercise and a low-energy balanced diet. The intervention lasted for 8 weeks for both groups. The differences in energy intake during the intervention, as well as body weight, body mass index (BMI), waist circumference, fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG), total cholesterol (TC), and adiponectin levels before and after the intervention were compared between the two groups. Measurement data with normal distribution were expressed as Mean±SD, inter-group comparisons were performed by independent samples t-test, and within-group comparisons before and after treatment were performedby paired t-test. Counting data were expressed as case (%), and inter-group comparisons were performed by χ2 test. Results:The energy intake during the intervention was lower in the observation group than in the control group [(1 450±180) kcal/d vs. (1 780±205) kcal/d, t=-5.35, P<0.001]. Before the intervention, there were no statistically significant differences in body weight, BMI and waist circumference between the two groups (all P>0.05). After 8 weeks of intervention, body weight, BMI, and waist circumference decreased significantly compared to pre-intervention levels in both groups [Control group: (62±12) kg vs. (64±13) kg, (26.4±2.9) kg/m 2 vs. (27.9±3.4) kg/m 2, (85±7) cm vs. (91±7) cm, t=7.23, 9.07, 12.31, respectively, all P<0.001; Observation group: (59±16) kg vs. (65 ± 17) kg, (23.3±4.3) kg/m 2 vs. (28.5±4.1) kg/m 2, (82±9) cm vs. (92±10) cm, t=24.90, 17.93, 21.40, respectively, all P<0.001]. Furthermore, the post-intervention values for body weight, BMI, and waist circumference were significantly lower in the observation group than in the control group ( t=-10.89, -18.92, -5.16, respectively, all P<0.001). Before the intervention, there were no statistically significant differences in FBG, FINS, TG, TC, or adiponectin levels between the two groups (all P>0.05). After 8 weeks of intervention, FBG, FINS, TG, and TC levels decreased significantly compared to pre-intervention levels in both groups [Control group: (4.99±0.26) mmol/L vs. (5.22±0.27) mmol/L, (24±6) mU/L vs. (26±8) mU/L, (1.3±0.5) mmol/L vs. (1.5±0.4) mmol/L, (4.3±0.6) mmol/L vs. (4.5±0.6) mmol/L, t=19.75, 6.69, 7.64, 18.27, respectively, all P<0.001; Observation group: (4.64±0.34) mmol/L vs. (5.31±0.26) mmol/L, (16±5) mU/L vs. (21±10) mU/L, (1.0±0.3) mmol/L vs. (1.4±0.5) mmol/L, (4.0±0.8) mmol/L vs. (4.5±0.8) mmol/L, t=19.66, 8.82, 11.26, 22.68, respectively, all P<0.001]. Adiponectin levels increased significantly in both groups [Control group: (8.0±1.2) mg/L vs. (6.8±1.1) mg/L , t=8.38, P<0.001; Observation group: (8.8±1.1) mg/L vs. (6.8±1.2) mg/L, t=23.78, P<0.001], while the improvements in all these glycolipid metabolic parameters were significantly greater in the observation group than in the control group ( t=3.70, 2.76, 2.42, 2.22,2.14, P=0.001, 0.009, 0.020, 0.027, 0.039). Conclusion:The combined intervention of a low-energy balanced diet and exercise can reduce body weight, blood glucose, and blood lipid levels in obese children, thereby improving their glycolipid metabolism.

Antibody humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic antibodies originated from animal models.Computational suggestions have long been desired,but available tools focused on immunogenicity calculation of whole antibody sequences and sequence segments,missing the individual residue sites.This study introduces Site-specific Immunogenicity for Therapeutic Antibody(SITA),a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody,but also individual residues,based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures.A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Antibody-Antibody structural complexes.On an independent testing dataset derived from 13 Antibody-Antibody structural complexes,SITA successfully predicted the epitope sites for Antibody-Antibody structures with a receiver operating characteristic(ROC)-area unver the ROC curve(AUC)of 0.85 and a precision-recall(PR)-AUC of 0.305 at the residue level.Furthermore,the SITA score can significantly distinguish immunogenicity levels of whole human antibodies,therapeutic antibodies and non-human-derived antibodies.More importantly,analysis of an additional 25 thera-peutic antibodies revealed that over 70％of them were detected with decreased immunogenicity after modification compared to their parent variants.Among these,nearly 66％antibodies successfully iden-tified actual modification sites from the top five sites with the highest SITA scores,suggesting the ability of SITA scores for guide the humanization of antibody.Overall,these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.

Background Per- and polyfluoroalkyl substances (PFAS) are a class of persistent organic pollutants widely used in various products, leading to population exposure and long-term accumulation. At present, there is a lack of research on the relationships between pre-pregnancy PFAS and menstrual characteristics among women undergoing assisted reproductive technology (ART) in China. Objective To explore the relationships between pre-pregnancy PFAS exposure among women undergoing ART and menstrual characteristics prior to assisted reproductive treatment. Methods This study employed a cross-sectional research design, recruiting women undergoing ART treatment at the Reproductive Clinic of the International Peace Maternity & Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, from 2017 to 2020 as study participants. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used to detect 42 types of PFAS in pre-pregnancy serum samples. Questionnaires were administered to collect information on demographic characteristics, lifestyle habits, and menstrual characteristics (average menstrual cycle length, average menstrual period length, menstrual irregularities, and menstrual bleeding volume) of women undergoing ART. Multiple linear regression, binary logistic regression, and multinomial logistic regression analyses were performed to investigate the relationships between individual PFAS exposure before pregnancy and menstrual characteristics among ART women. Additionally, weighted quantile sum (WQS) model was applied to analyze the association between PFAS mixtures and menstrual characteristics. Results In the pre-pregnancy serum samples of the study population, 15 PFAS were detected in more than 60% of the samples, including perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), perfluorobutanesulfonic acid (PFBS), perfluorohexanesulfonic acid (PFHxS), perfluoroheptanesulfonic acid (PFHpS), perfluorooctanesulfonic acid (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 chlorinated polyfluorinated ether sulfonate (8:2 Cl-PFESA), perfluoro-2-propoxypropanoic acid (HFPO-DA), perfluoro-2-methoxyacetic acid (PFMOAA), and perfluoro-(3,5,7,9,11-pentaoxadodecanoic) acid (PFO5DoDA). Among them, PFOA had the highest median concentration of 9.160 ng·mL⁻¹. The single PFAS exposure analysis revealed a positive correlation between PFAS and irregular menstrual cycles. Specifically, for every natural-log unit (e) increase in PFOA, PFBS, or PFHxS level, the incidence of irregular menstrual cycles increased by 57%, 42%, or 39%, respectively. Most PFAS were positively correlated with the average number of menstrual cycle days, such as PFHpA (b=1.08, 95%CI: 0.11, 2.05), PFOA (b=1.69, 95%CI: 0.39, 3.00), PFBS (b=1.23, 95%CI: 0.25, 2.22), PFHxS (b=1.47, 95%CI: 0.61, 2.32), PFHpS (b=1.48, 95%CI: 0.35, 2.61), and 6:2 Cl-PFESA (b=0.90, 95%CI: 0.08, 1.72). Furthermore, levels of PFHpA (OR=1.39, 95%CI: 1.06, 1.82), PFOA (OR=1.58, 95%CI: 1.09, 2.30), PFBS (OR=1.37, 95%CI: 1.04, 1.80), PFHxS (OR=1.34, 95%CI: 1.05, 1.71), PFHpS (OR=1.53, 95%CI: 1.10, 2.14), and 6:2 Cl-PFESA (OR=1.34, 95%CI: 1.06, 1.70) were positively correlated with low menstrual blood volume, while PFOA (OR=0.40, 95%CI: 0.23, 0.71), PFHpS (OR=0.45, 95%CI: 0.29, 0.71), and HFPO-DA (OR=0.68, 95%CI: 0.48, 0.97) were negatively correlated with high menstrual blood volume. The mixed exposure model showed that PFAS mixtures were positively correlated with the average number of menstrual cycle days (b=1.60, 95%CI: 0.49, 2.71), irregular menstrual cycles (OR=1.77, 95%CI: 1.19, 2.63), and low menstrual blood volume (OR=1.59, 95%CI: 1.08, 2.35), but negatively correlated with high menstrual blood volume (OR=0.40, 95%CI: 0.22, 0.73). Conclusion Women undergoing ART in Shanghai are widely exposed to PFAS prior to conception. Exposure to PFAS before pregnancy may be related to menstrual characteristics among women seeking ART before undergoing fertility treatments, but additional data from larger populations are required to validate the findings of this study.

Antibody (Ab) humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic Abs originated from animal models. Computational suggestions have long been desired, but available tools focused on immunogenicity calculation of whole Ab sequences and sequence segments, missing the individual residue sites. This study introduces Site-specific Immunogenicity for Therapeutic Antibody (SITA), a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody, but also individual residues, based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures. A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Ab-Ab structural complexes. On an independent testing dataset derived from 13 Ab-Ab structural complexes, SITA successfully predicted the epitope sites for Ab-Ab structures with a receiver operating characteristic (ROC)-area unver the ROC curve (AUC) of 0.85 and a precision-recall (PR)-AUC of 0.305 at the residue level. Furthermore, the SITA score can significantly distinguish immunogenicity levels of whole human Abs, therapeutic Abs and non-human-derived Abs. More importantly, analysis of an additional 25 therapeutic Abs revealed that over 70% of them were detected with decreased immunogenicity after modification compared to their parent variants. Among these, nearly 66% Abs successfully identified actual modification sites from the top five sites with the highest SITA scores, suggesting the ability of SITA scores for guide the humanization of antibody. Overall, these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.

Objective To investigate the effects of integrating pelvic floor magnetic stimulation and medium-frequency pulsed electrotherapy with biofeedback on alleviating obstructed defecation symptoms in patients diagnosed with pelvic floor spasm syndrome.Methods A total of 133 patients diagnosed with pelvic floor spasm syndrome at the Gastrointestinal Surgery Outpatient and Inpatient Departments of the Third Hospital of Hebei Medical University between January 2017 and January 2025 were enrolled in this study.All patients underwent two sessions of conventional biofeedback therapy.According to the additional treatments they received,the patients were catego-rized into four groups:the Control group(received biofeedback therapy only);the Magnetic Stimulation group(received two additional sessions of pelvic floor magnetic stimulation);the Electrical Stimulation group(received two additional sessions of medium-frequency pulse electrical therapy);and the Magnetic-Electric Combined group(received two additional sessions of both pelvic floor magnetic stimulation and medium-frequency pulse electrical therapy).The improvement in obstructed defecation symptoms was evaluated before treatment,after treatment,and at the 3-month follow-up across all four groups.Results A total of 133 patients diagnosed with pelvic floor spasm syndrome were enrolled in this study.After a 3-month follow-up period,8 patients were lost to follow-up(6.0%).Consequently,125 patients completed the follow-up and were included in the final analysis.These patients were distributed across four groups:the control group(n=32),the magnetic stimulation group(n=30),the electrical stimulation group(n=31),and the combined magneto-electric stimulation group(n=32).Compared with biofeedback therapy alone,combination therapy led to a greater reduction in the need for manual assistance during defecation,the sensation of incomplete evacuation,and the requirement for straining during defecation,with the most pronounced improvements observed in the combined magneto-electric stimulation group.Conclusions The integration of biofeedback,pelvic floor magnetic stimulation,and medium-frequency pulse electrotherapy can significantly alleviate symptoms including straining during defecation,the sensation of incomplete bowel evacua-tion,and reduce the need for manual assistance.Moreover,this combined approach contributes to the stabilization and maintenance of therapeutic effects in the short term.

Objective:To explore the clinical and biochemical characteristics of patients with hyperuricemia according to different pathophysiological subtypes. This may facilitate rapid identification of each subtype in clinical settings and provide evidence for personalized urate-lowering treatment.Methods:Patients diagnosed with hyperuricemia at the Department of Endocrinology and Metabolism, Tenth People′s Hospital of Tongji University between October 2015 and January 2024 were included. Based on 24-h urinary uric acid excretion(UUE) and the fractional excretion of uric acid(FEUA), patients were classified into four subtypes: renal uric acid underexcretion type(RUE), renal uric acid overload type(ROL), combined type and renal normal type. Clinical and biochemical variables-including sex, age, BMI, smoking history, comorbidities, blood glucose, and serum uric acid-were analyzed. Binary logistic regression was used to identify factors associated with each subtype.Results:Among 2 073 patients with hyperuricemia, 55.8% were RUE type, 6.9% were ROL type, 31.3% were combined type and 6.0% were renal normal type. RUE type had lower blood glucose levels and fewer cases of diabetes [ OR=0.685(95% CI 0.478-0.980), P<0.05]. ROL type showed a higher incidence of tophi, positively correlated with smoking history [ OR=1.672(95% CI 1.009-2.771), P<0.05], and negatively correlated with serum uric acid levels [ OR=0.994(95% CI 0.990-0.998), P=0.001]. Combined type had the youngest onset age, shortest disease duration, and the fewest comorbidities, and was associated with higher BMI [ OR=1.035(95% CI 1.001-1.070), P<0.05]. Renal normal type had the oldest age of onset, the highest proportion of female patients and comorbidities, and was associated with lower serum uric acid levels[ OR=0.994(95% CI 0.989-0.998), P=0.007], higher BMI[ OR=1.064(95% CI 1.003-1.129), P<0.05], and increased tophi incidence[ OR=2.261(95% CI 1.206-4.237), P=0.011]. Conclusion:Each pathophysiological subtype of hyperuricemia exhibits distinct clinical and biochemical characteristics, which may serve as useful references for subtype identification and personalized management in clinical practice.

Objective To explore the mechanism of TubA in the treatment of ulcerative colitis in mice,and to lay a foundation for the treatment strategy of ulcerative colitis.Methods Twenty C57BL/6 mice aged 6-8 weeks were randomly divided into 4 groups(n=5):the control group drank pure water every day,the model group and the treatment groups drank 3％dextran sulfate sodium(DSS)every day,and the treatment groups were injected with 10 mg/kg TubA and 20 mg/kg TubA every day from the third day,respectively.The weight changes of mice in all groups were recorded.Nine days later,the serum of mice was collected,and the expression levels of inflammatory factors IL-1β,IL-6 and IL-10 in serum were detected by ELISA.HE staining was used to observe the pathological changes of the mouse colon.The expression of myeloperoxidase(MPO)was detected by immunohistochemistry,the mRNA levels of inflammatory factors IL-1β,IL-6 and IL-10 were detected by RT-qPCR,and the expressions of GPX4 and FTH were detected by immunohistochemistry.The mRNA and protein expression levels of GPX4,GCLM,FTH,Nrf2,Keap1 and HO-1 in colon tissues were detected by RT-qPCR and Western blotting.Results Compared with the control group,the body weight and colon length of the model group decreased significantly.HE staining showed that inflammatory cells infiltrated the mucosa and submucosa of colon tissue,goblet cells were lost and crypt structure disordered and disappeared.Immunohistochemistry showed that the expression of MPO and FTH proteins were significantly increased,while the expression of GPX4 protein was significantly decreased(P＜0.05).The mRNA and protein expression levels of IL-1β and IL-6 were significantly increased,while the mRNA and protein expression levels of IL-10 were significantly decreased(P＜0.05).The mRNA and protein expression levels of FTH,Nrf2 and HO-1 were significantly increased,while the mRNA and protein expression levels of GPX4,GCLM and Keap1 were significantly decreased(P＜0.05).After TubA treatment,compared with the model group,all these changes mentioned above suppressed(P＜0.05).Conclusion TubA may reduce ulcerative colitis symptoms by inhibiting ferroptosis,providing new ideas for the treatment of ulcerative colitis.

Objective To investigate the occurrence and characteristics of Antineutrophil cytoplasmic antibody(ANCA)associated vasculitis induced by methimazole,and to provide references for clinical safe drug use.Methods Case reports of ANCA associated vasculitis induced by methimazole published in Wanfang,CNKI,PubMed,and Web of Science were searched from the inception to October 31 st,2023.Demographic characteristics,drug use,complications,treatment and outcome were analyzed using descriptive statistical method.Results A total of 14 patients from 14literature were included.There were 3 males and 11 females with ages ranging from 8 to 79 years,with a mean age of(47.79±23.47)years.Four patients developed symptoms within 1 year,nine patients developed symptoms from 2 to 12 years,and 1 patient developed symptoms 24 years after medication.ANCA associated vasculitis affected kidney in 5 patients,lung and skin in 5patients,vision in 2 patients and heart in 2 patients.All patients discontinued methimazole,2 patients improved spontaneously without treatment,1 patient improved after anti-infection,and all others received hormonal or immunosuppressive therapy.1 patient developed death,and all others improved or were cured after treatment.Conclusions ANCA-associated vasculitis is a rare adverse reactionof methimazole.Most patients have a long latency period before the onset of disease,mainly involving multiple organs such asskin,kidney,lung,and eyesight.Clinicians should pay attention to differentiate it from primary vasculitis and discontinue the drug as soon as possible.When serious organ damage occurs,glucocorticoids and immunosuppressants should be adminstered promptly to avoid aggravation of the disease and endangerment of life.