Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

AIM To investigate the variations in mercury dissolution from HgS-containing traditional medicines in three kinds of simulated gastrointestinal dissolution media.METHODS 39 batches of 15 types of HgS-containing traditional medicines were collected,total mercury content and dissolved mercury concentrations in simulated gastric fluid,simulated intestinal fluid,and L-cysteine-containing simulated intestinal fluid were measured.The maximum daily intake of total mercury and soluble mercury was calculated based on the maximum daily clinical dosage.RESULTS Among the 15 types of medicines,the maximum daily intake of total mercury varied by 156 times,the daily intake of soluble mercury varied by 3 502 times in simulated gastric fluid,313 times in simulated intestinal fluid,and 10 663 times in L-cysteine-containing simulated intestinal fluid,approximately.CONCLUSION For the 15 types of HgS-containing traditional medicines,the daily maximum intake of soluble mercury showed greater variations than that of total mercury.Soluble mercury concentration is more closely correlated with intestinal absorption of mercury and thus represents a more rational quality control indicator for HgS-containing traditional medicines.

Objective To assess the effectiveness of the Gasdermin D C-terminal fragment(GSDMD-CT)as a novel plasma biomarker for the clinical diagnosis of sepsis.Methods Between July 2021 and November 2024,245 patients from Tangshan Gongren Hospital were enrolled in this study.In accordance with the diagnostic criteria for sepsis and the systemic inflammatory response syndrome(SIRS),patient samples were classified into the sepsis group and the SIRS group.Meanwhile,healthy individuals were selected as the healthy control(HC)group.Sepsis patients were further categorized into the Gram-positive bacterial group,the Gram-negative bacterial group,and the fungal group based on the type of pathogen infection.The levels of GSDMD-CT,C-reactive protein(CRP),and procalcitonin(PCT)were measured in all subjects.Nonparametric tests were employed to compare the differences in various indices among different groups.The diagnostic value of GSDMD-CT in sepsis was evalu-ated by constructing the receiver operating characteristic(ROC)curve.Spearman's correlation analysis was used to examine the relationships among GSDMD-CT,CRP,and PCT.Results The plasma GSDMD-CT levels in the sepsis group 23.02(16.71,33.01)pg/mL and in the SIRS group 16.52(11.26,22.22)pg/mL were significantly higher than those in the healthy control group 7.02(4.42,11.43)pg/mL(U=-10.175,-7.890,P<0.001).Moreover,the plasma GSDMD-CT levels in the sepsis group were significantly higher than those in the SIRS group(U=-2.941,P<0.05).In the Gram-positive bacterial group,the Gram-negative bacterial group,and the fungal group,the GSDMD-CT levels were 23.01(17.16,27.51)pg/mL,23.41(16.78,35.50)pg/mL,and 16.29(14.53,56.27)pg/mL,respectively.When compared with the healthy control group,the GSDMD-CT levels in these three groups were all significantly higher(P<0.05).However,there were no significant differences in GSDMD-CT levels among these three groups(P>0.05).The area under the curve(AUC)of plasma GSDMD-CT for diagnosing sepsis was 0.881(95%confidence interval:0.833～0.929),with a Youden index(YI)of 0.695,a sensitivity of 85.0%,and a specificity of 84.5%.Spearman correlation analysis indicated a weak correlation between GSDMD-CT and C-reactive protein(CRP)(r=0.32,P<0.001)and a positive correlation between GSDMD-CT and procalci-tonin(PCT)(r=0.65,P<0.001).Conclusion GSDMD-CT exhibits significant clinical value in the diagnosis of sepsis and holds great potential as a biomarker in the diagnostic process of sepsis.

BACKGROUND:Knee osteoarthritis is a common degenerative disease that significantly impacts patients'quality of life and increases the societal healthcare burden.Early and accurate diagnosis of knee osteoarthritis is crucial for the treatment and prognosis of patients.Traditional diagnostic methods are not only subjective and time-consuming but also do not guarantee consistently high accuracy.OBJECTIVE:To develop an automatic diagnostic method for knee osteoarthritis based on deep learning,utilizing deep learning networks to improve diagnostic accuracy and efficiency.METHODS:A new network model,YOLOV8-ViT,was proposed by replacing the backbone network of YOLOv8n with the Efficient-ViT network and incorporating attention mechanisms for the automatic identification and classification of X-ray images of knee osteoarthritis.The experimental dataset included 5 078 X-ray images of patients with knee osteoarthritis obtained from the Third Affiliated Hospital of Guangzhou University of Chinese Medicine.Three imaging physicians annotated the sites of knee osteoarthritis and classified them according to the Kellgren-Lawrence grading standard using Labelme software,and the results were combined.The evaluation indicators used in this study included Precision,F1 score,mean average precision(mAP),Recall,val/box_loss,val/cls_loss,and val/dfl_loss.RESULTS AND CONCLUSION:The experimental results showed that the YOLOV8-ViT model outperformed the YOLOv5n,YOLOv8n,and YOLOv9n models in terms of precision,mAP50,mAP50-95,F1 score,and Recall,while lowering val/box_loss,val/cls_loss,and val/dfl_loss by 0.496,0.45,and 0.523;1.037,0.305,and 0.728;and 0.267,0.654,and 0.854,respectively.These experimental data validate that this model has high detection accuracy.

Objective:To explore the short-term clinical effects of deep cervical lymph node-venous anastomosis in the treatment of Alzheimer’s disease (AD).Methods:A prospective exploratory study was conducted on the treatment of AD patients using the cervical deep lymph node-venous anastomosis technique in Scar and Wound Treatment Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, from September to October 2024. The patients underwent high-frequency ultrasound to locate deep cervical lymph nodes and the external jugular vein. Under general anesthesia, bilateral deep cervical lymph node-venous anastomoses were performed. Indocyanine green (ICG) lymphography was conducted via subcutaneous injection behind the ear to visualize lymph nodes in levels Ⅱ and Ⅲ. After making a skin incision along the posterior margin of the sternocleidomastoid muscle, the external jugular vein, internal jugular veins, and associated lymph nodes were exposed. Adjacent veins were selected for anastomosis of lymph node. Using microsurgical techniques, end-to-side or end-to-end anastomosis was completed for lymph nodes in levels Ⅱ and Ⅲ. Preoperative assessments included the mini-mental state examination (MMSE, a higher score indicates better cognitive function), Alzheimer’s disease assessment scale-cognitive subscale (ADAS-Cog, a higher score indicates greater impairment of cognitive function), Alzheimer’s disease cooperative study scale for activities of daily living (ADCS-ADL, a higher score indicates better ability to perform daily activity), and neuropsychiatric inventory (NPI, a higher score indicates more severe behavioral and emotional symptom). Postoperative follow-up included the same scales to observe changes in cognitive function, activities of daily living, and emotional communication.Results:Four patients (1 male, 3 females, aged 58-79 years) with AD were included. All were diagnosed based on cerebrospinal fluid biomarkers. All patients successfully underwent bilateral deep cervical lymph node-venous anastomoses. On average, 4.3 (2-7 per person) anastomoses were performed per patient. Surgical procedures lasted an average of 6.5 h (5.5-8.5 h) with minimal blood loss (less than 50 ml). Patients resumed normal activity within 6 hours postoperatively and were discharged after an average of 4.1 d (3.5-5.0 d). Postoperative complications included one case each of aspiration pneumonia, lower limb venous thrombosis, and transient delirium, all of whom resolved without long-term effects. Clinical symptoms, including memory decline, mood swings, and anxiety, showed varying degrees of improvement. Patients reported enhanced quality of life, emotional stability, and social engagement, confirming the procedure’s safety and potential cognitive benefits. At one month postoperatively, the MMSE scores of the four patients increased by an average of 0.8 points compared to preoperative levels. Additionally, the two patients who completed the ADAS-Cog assessments showed a decrease in their scores (reduced by 1.0 points and 11.3 points, respectively, compared to preoperative scores), indicating a certain degree of improvement in cognitive function during this period. The ADCS-ADL and NPI scores of four patients varied significantly, without showing any clear pattern.Conclusion:Lymphovenous anastomosis of the deep cervical lymph node-venous anastomosis may provide a new surgical intervention approach for AD, but further large-scale studies and long-term follow-up are needed to validate its safety and effectiveness.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To investigate the effectiveness and safety of lacosamide (LCM) in pregnant women with epilepsy.Methods:A retrospective study was conducted involving 6 pregnant women with epilepsy who were treated with LCM at the Electroencephalogram Monitoring Center of the Department of Neurology, Xijing Hospital of Air Force Military Medical University from January 2022 to June 2023. Their electroclinical characteristics, seizures during pregnancy, breastfeeding, and follow-up were summarized.Results:The 6 patients were aged 22 to 30 years at the time of pregnancy. Three patients were treated with monotherapy, with a daily dose of LCM ranging from 150 mg to 200 mg, while the other 3 patients were treated with combination therapy, with a daily dose of 150 mg. The seizures of 5 patients decreased during pregnancy compared with progestation except for the case 2 without adherence to Medication. No malformations were observed in the newborns, with the Apgar scores of 9-10 at 1 minute and 5 minutes after birth. The infants showed normal growth, development, intelligence, and motor skills in subsequent assessments. Two patients breastfed their infants, 1 for 6 months and the other for 14 months by the last follow-up, with a daily LCM dose of 150 mg to 300 mg during the breastfeeding. No adverse reactions were observed in the infants.Conclusion:The addition of LCM during pregnancy and lactation showed good effectiveness and safety, with no observed birth malformations.

AIM To investigate the variations in mercury dissolution from HgS-containing traditional medicines in three kinds of simulated gastrointestinal dissolution media.METHODS 39 batches of 15 types of HgS-containing traditional medicines were collected,total mercury content and dissolved mercury concentrations in simulated gastric fluid,simulated intestinal fluid,and L-cysteine-containing simulated intestinal fluid were measured.The maximum daily intake of total mercury and soluble mercury was calculated based on the maximum daily clinical dosage.RESULTS Among the 15 types of medicines,the maximum daily intake of total mercury varied by 156 times,the daily intake of soluble mercury varied by 3 502 times in simulated gastric fluid,313 times in simulated intestinal fluid,and 10 663 times in L-cysteine-containing simulated intestinal fluid,approximately.CONCLUSION For the 15 types of HgS-containing traditional medicines,the daily maximum intake of soluble mercury showed greater variations than that of total mercury.Soluble mercury concentration is more closely correlated with intestinal absorption of mercury and thus represents a more rational quality control indicator for HgS-containing traditional medicines.

Objective:To investigate the effects of moxibustion at Tianshu(ST25)acupoint on 5-fluorouracil(5-FU)-induced intestinal mucositis(IM)and its underlying mechanisms.Methods:Eighteen C57BL/6 male mice were randomly divided into four groups:normal control(NC),IM model(IM),moxibustion 15 min(MO 15 min),and moxibustion 30 min(MO 30 min).The IM model was established via intraperitoneal injection of 5-FU.Pathological changes in colon tissues were observed using hematoxylin and eosin(HE)staining.Protein expression levels of peroxisome proliferator-activated receptor alpha(PPARα),nuclear factor kappa-B(NF-κB),phosphorylated NF-κB(p-NF-κB),NOD-like receptor thermal protein domain associated protein 3(NLRP3),caspase-1,interleukin-1β(IL-1β),and interleukin-18(IL-18)were analyzed via Western blot,ELISA,and immunohistochemistry.Results:Compared with the NC group,the IM group showed significantly shortened colon length(P＜0.05),exhibited mucosal damage,inflammatory cell infiltration,and glandular disorder,along with upregulated protein expression of p-NF-κB,NLRP3,IL-1β,IL-18,and caspase-1(P＜0.05),and downregulated PPARα expression(P＜0.05).After moxibustion intervention,the MO 15 min group demonstrated increased intestinal length(P＜0.05),reduced pathological scores(P＜0.05),significantly downregulated expression of NLRP3,p-NF-κB,IL-1β,and IL-18(P＜0.05),and elevated PPARα expression(P＜0.05),while total NF-κB protein levels remained unchanged.Conclusion:Moxibustion at Tianshu(ST25)acupoint may alleviate 5-FU-induced intestinal mucosal inflammatory responses by activating PPARα to suppress the NF-κB/NLRP3 inflammasome signaling pathway.