Background Lead is a typical persistent environmental pollutant that can accumulate in bones for decades. During pregnancy, alterations in calcium metabolism promote the mobilization of bone lead, resulting in secondary exposure; however, the mechanisms by which pregnancy-associated bone lead mobilization affects maternal renal function remain unclear. Objective To investigate the role of mitochondrial dysfunction in pregnancy-related bone lead mobilization-induced renal injury. Methods Newly weaned female Wistar rats were randomly assigned to a control or a lead-exposed group administered either 0.05% sodium acetate or 0.05% lead acetate in drinking water. Following a 4-week lead exposure and a 4-week washout period, the females were co-housed with healthy age-matched males for mating. Rats were sacrificed at early (gestational day 3) and late (gestational day 17) pregnancystages, respectively. Renal histopathology was assessed using hematoxylin and eosin staining staining. Mitochondria-related indicators, including oxidative stress, inflammatory responses, and energy metabolism, were measured. Differential metabolites were identified using serum metabolomics. Results Renal injury in the lead-exposed pregnant rats progressed in a time-dependent manner, characterized by degeneration of proximal tubular epithelial cells, glomerular hyaline changes, and interstitial inflammatory cell infiltration. Repeated measures ANOVA indicated a significant interaction between the treatment factor (lead exposure) and the temporal factor (gestational stage) on renal injury (P<0.001). Further analysis of mitochondrial function-related indicators in late-pregnancy renal tissue revealed that the lead exposure group exhibited significantly increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) (P<0.05), accompanied by a reduction in superoxide dismutase (SOD) and reduced glutathione (GSH) activities (P<0.05); regarding inflammatory markers, levels of interleukin-18 (IL-18) and interleukin-1β (IL-1β) were elevated (P<0.01), whereas interleukin-33 (IL-33) was decreased in the lead-exposed group (P<0.05); energy metabolism-related indicators, including adenosine triphosphate (ATP) level, Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities, and mitochondrial respiratory chain complexes I, III, and V activities, were significantly reduced (P<0.05) in the lead-exposed gorup. The typical differential metabolite N-methylisoleucine, identified through serum metabolomics analysis, was negatively correlated with blood lead levels, kidney injury scores, and IL-1β, while positively correlated with catalase (CAT) activity and Ca²⁺-Mg²⁺-ATPase. Conclusions Mitochondrial dysfunction may play a critical role in renal injury induced by bone lead mobilization during late gestation.

ObjectiveA middle cerebral artery occlusion (MCAO) mouse model is established by electrocoagulation of the middle cerebral artery. The study examines the mechanism by which exosomes (EXO) derived from human amniotic mesenchymal stem cells (hAMSCs) improve ischemic stroke and regulate neural ferroptosis-related injury. MethodsThirty-two SPF-grade male C57BL/6J mice aged 6 - 8 weeks were randomly divided into four groups (n=8 per group): sham group (Sham), model group (MCAO), MCAO plus normal saline group (MCAO+NaCl), and MCAO plus exosome group (MCAO+EXO). The mouse MCAO model was established by electrocoagulation of the middle cerebral artery. Mice in the Sham group underwent exposure of the middle cerebral artery without electrocoagulation. Twenty-four hours before MCAO induction, mice in the MCAO+EXO group received a tail vein injection of 100 μL of exosomes derived from the culture supernatant of hAMSCs at a concentration of 9.5×10¹¹ particles/mL. Mice in the MCAO+NaCl group were injected with an equal volume of normal saline via the tail vein. Twenty-four hours after model establishment, neurological deficits were evaluated using the Longa neurological deficit scoring system. Cerebral infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Hematoxylin and eosin (HE) staining was performed to evaluate morphological changes of neurons in the ischemic brain regions. The contents of ferrous iron (Fe²⁺), malondialdehyde (MDA), total glutathione (total GSH), oxidized glutathione (GSSG), and reduced glutathione (GSH) in the infarct core and peri-infarct regions were determined using microcolorimetric assays to evaluate differences among groups. The mRNA expression levels of ferroptosis-related factors, including nuclear factor erythroid 2-related factor 2 (NRF2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in the infarct core and peri-infarct regions were measured by real-time quantitative PCR. Protein expression levels of NRF2, SLC7A11, and GPX4 in the infarct and peri-infarct regions of each group were analyzed by Western blotting. ResultsCompared with the MCAO group, the Longa neurological deficit score was significantly reduced in the MCAO+EXO group (P<0.01). Prominent cerebral infarction was observed in the MCAO group, whereas the infarct volume ratio was markedly decreased in the MCAO+EXO group compared with the MCAO group (P<0.001). Histopathological analysis revealed that mice in the MCAO group exhibited obvious neuronal damage, including cytoplasmic vacuolar degeneration, nuclear pyknosis and fragmentation, unclear nuclear structure, and disorganized neuronal arrangement, compared with the Sham group. In contrast, neurons in the MCAO+EXO group showed relatively preserved morphology, with intact cellular structures and large, regular nuclei located centrally within the cells. Biochemical analysis demonstrated that Fe²⁺ and MDA levels in the infarct core and peri-infarct regions were significantly increased in the MCAO group compared with the Sham group (P<0.001). These levels were significantly reduced in the MCAO+EXO group compared with the MCAO group (P<0.01). In addition, total glutathione (total GSH), oxidized glutathione (GSSG), and reduced glutathione (GSH) levels were markedly decreased in the MCAO group relative to the Sham group (P<0.01). Compared with the MCAO group, the MCAO+EXO group exhibited significantly increased levels of total GSH and GSH (P<0.001), while no significant change was observed in GSSG levels (P>0.05). Furthermore, both mRNA and protein expression levels of nuclear factor erythroid 2-related factor 2 (NRF2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) were significantly downregulated in the MCAO group compared with the Sham group (P<0.01, P<0.001). In contrast, both mRNA and protein expression levels of NRF2, SLC7A11, and GPX4 were significantly upregulated in the MCAO+EXO group compared with the MCAO group (P<0.05). ConclusionIn the mouse MCAO model, tail vein injection of exosomes derived from hAMSCs can improve motor function, reduce infarct area, protect neuronal cell morphology, and reduce the degree of nerve injury. Exosomes may exert a protective effect by activating the NRF2/SLC7A11/GPX4 pathway and reducing ferroptosis in neuronal cells of MCAO model mice.

Background and Aims:Minimally invasive surgery,represented by laparoscopic techniques,plays a vital role in the treatment of gastric cancer.However,postoperative infectious complications remain a key factor affecting patient recovery and prognosis.This study was performed to identify the risk factors associated with early(≤1 month)infectious complications after laparoscopic surgery for gastric cancer,providing a reference for clinical prevention strategies.Methods:A retrospective analysis was conducted on 1 572 patients who underwent laparoscopic surgery for gastric cancer at the First Affiliated Hospital of Xi'an Jiaotong University from March 2020 to February 2024.Patients were divided into infection and non-infection groups based on the occurrence of postoperative infectious complications.Univariate and multivariate Logistic regression analyses were performed to identify related risk factors.Results:Among the 1 572 patients,194 cases(12.3％)developed early postoperative infectious complications,including intra-abdominal infections(4.1％),surgical site infections(3.7％),and pulmonary infections(5.6％).Univariate analysis revealed that a history of diabetes,pulmonary disease,smoking,and preoperative anemia and hypoalbuminemia were significantly associated with postoperative infections(all P＜0.05).Multivariate analysis indicated that a history of diabetes(OR=6.927,95％CI=4.194-12.935),smoking(OR=3.079,95％CI=2.261-4.913),and preoperative albumin＜35 g/L(OR=0.572,95％CI=0.302-1.578)were independent risk factors for early postoperative infectious complications.Conclusion:A history of diabetes,smoking,and preoperative hypoalbuminemia are closely associated with the occurrence of early postoperative infectious complications after laparoscopic gastric cancer surgery.Clinical attention should be paid to perioperative metabolic,nutritional,and lifestyle management,and early intervention for high-risk patients may help reduce the incidence of complications,improve recovery,and enhance treatment outcomes.

Idiopathic scoliosis is the most common spinal deformity among adolescents. Spinal correction surgery is a complex procedure with a long operative duration and extensive tissue damage, frequently resulting in chronic postoperative pain. This type of pain imposes significant physical and psychological burdens on patients, as well as considerable economic strain on families and society. This paper provides an overview of the concept, prevalence, assessment tools, influencing factors, and preventive and therapeutic strategies for chronic postoperative pain in adolescents with idiopathic scoliosis. The aim is to offer a reference for managing postoperative chronic pain in these patients and to inform further research in this area.

Objective To investigate the pharmacokinetic(PK)profile of ripretinib in patients with advanced gastrointestinal stromal tumors(GISTs)in real-world settings.Methods The PK data of eight advanced GIST patients treated with ripretinib and the steady-state trough concentration(Cmin)blood samples of 54 advanced GIST patients treated with ripretinib were collected from November 2023 to March 2025 at the First Affiliated Hospital of Sun Yat-sen University.A validated liquid chromatography-tandem mass spectrometry method was used to quantify ripretinib and DP-5439 concentrations.The PK profiles of ripretinib were characterized.Cmin was compared across various dosages.The correlations among PK parameters of ripretinib and DP-5439,and clinical features impacting PK were explored.Results All patients reached Cmin approximately 24 hours post-dose for ripretinib and DP-5439.The median time to maximum con-centration(Tmax)for both ripretinib and DP-5439 was 3.16 hours.The steady-state Cmin,maximum plasma concentration(Cmax),and area under the plasma concentration-time curve from 0 to 24 hours(AUC0-24 h)of ripretinib,DP-5439,and their combined total were found to be highly correlated(all r>0.85,all P<0.05).In patients receiving 150 mg once-daily(n=44),the median Cmin(range)was 381.66(40.90-1 045.48)ng/mL for ripretinib,589.08(25.28-1 168.11)ng/mL for DP-5439,and 998.00(66.18～2 381.48)ng/mL for total,with coeffi-cients of variation(CVs)of 59.4%,57.2%,and 53.6%.In the 300 mg group(n=11),the median Cmin(range)was 1 024.51(251.36-2 030.51)ng/mL for ripretinib,1 122.34(111.54-2 682.57)ng/mL for DP-5439,and 1 924.58(404.37-4 766.08)ng/mL for total,with CVs of 59.5%,57.3%,and 54.8%.Univariate analysis showed that no significant correlation was found between age or BMI and the dose-corrected Cmin of ripretinib and DP-5439(all P>0.05),and the median dose-corrected Cmin of ripretinib and DP-5439 was slightly lower in male patients than in female patients(P<0.05).In the multiple linear regression analysis,male patients were observed to have a lower median dose-cor-rected Cmin of DP-5439 than female patients(P=0.024),but no statistical difference was found in that of ripretinib(P>0.05).Conclusions In advanced GIST patients receiving ripretinib,ripretinib and DP-5439 reached Cmin 24 hours post-dose,just before the next administra-tion.The ripretinib,DP-5439,and total Cmin showed significant correlations with their AUC0-24 h,which indicated that Cmin could serve as an indicator of ripretinib exposure.The PK features of ripretinib in advanced GIST patients exhibit significant inter-individual variability.

Purpose: This study aimed to evaluate the contrast-enhanced ultrasound with Sonazoid (Sonazoid-CEUS) features of hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). Methods: In this retrospective study, patients who underwent surgical resection and were histopathologically diagnosed with NAFLD or cirrhosis-related HCC were included. All patients received Sonazoid-CEUS examinations within 1 week prior to hepatic surgery. The enhancement patterns of HCC lesions were evaluated and compared between the two groups according to the current World Federation for Ultrasound in Medicine and Biology guidelines. Multivariate logistic regression analysis was used to assess the correlations between Sonazoid-CEUS enhancement patterns and clinicopathologic characteristics. Results: From March 2022 to April 2023, a total of 151 patients with HCC were included, comprising 72 with NAFLD-related HCC and 79 with hepatitis B virus (HBV) cirrhosis–related HCC. On Sonazoid-CEUS, more than half of the NAFLD-related HCCs exhibited relatively early and mild washout within 60 seconds (54.2%, 39/72), whereas most HBV cirrhosis–related HCCs displayed washout between 60 and 120 seconds (46.8%, 37/79) or after 120 seconds (39.2%, 31/79) (P<0.001). In the patients with NAFLD-related HCC, multivariate analysis revealed that international normalized ratio (odds ratio [OR], 0.002; 95% confidence interval [CI], 0.000 to 0.899; P=0.046) and poor tumor differentiation (OR, 21.930; 95% CI, 1.960 to 245.319; P=0.012) were significantly associated with washout occurring within 60 seconds. Conclusion Characteristic Sonazoid-CEUS features are useful for diagnosing HCC in patients with NAFLD.

Purpose: This study aimed to evaluate the contrast-enhanced ultrasound with Sonazoid (Sonazoid-CEUS) features of hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). Methods: In this retrospective study, patients who underwent surgical resection and were histopathologically diagnosed with NAFLD or cirrhosis-related HCC were included. All patients received Sonazoid-CEUS examinations within 1 week prior to hepatic surgery. The enhancement patterns of HCC lesions were evaluated and compared between the two groups according to the current World Federation for Ultrasound in Medicine and Biology guidelines. Multivariate logistic regression analysis was used to assess the correlations between Sonazoid-CEUS enhancement patterns and clinicopathologic characteristics. Results: From March 2022 to April 2023, a total of 151 patients with HCC were included, comprising 72 with NAFLD-related HCC and 79 with hepatitis B virus (HBV) cirrhosis–related HCC. On Sonazoid-CEUS, more than half of the NAFLD-related HCCs exhibited relatively early and mild washout within 60 seconds (54.2%, 39/72), whereas most HBV cirrhosis–related HCCs displayed washout between 60 and 120 seconds (46.8%, 37/79) or after 120 seconds (39.2%, 31/79) (P<0.001). In the patients with NAFLD-related HCC, multivariate analysis revealed that international normalized ratio (odds ratio [OR], 0.002; 95% confidence interval [CI], 0.000 to 0.899; P=0.046) and poor tumor differentiation (OR, 21.930; 95% CI, 1.960 to 245.319; P=0.012) were significantly associated with washout occurring within 60 seconds. Conclusion Characteristic Sonazoid-CEUS features are useful for diagnosing HCC in patients with NAFLD.

[摘 要] 目的：探究地塞米松联合阿比特龙对去势抵抗性前列腺癌（CRPC）患者尿流动力学、外周血循环肿瘤细胞雄激素受体剪切变异体7（AR-V7）、人同源盒基因B13（HoxB13）水平及生存预后的影响。方法：回顾性选取本院收治的114例CRPC患者病历资料，根据治疗方案分为对照组（予以0.5 mg地塞米松治疗，n = 51）和观察组（予以0.5 mg地塞米松联合1 000 mg阿比特龙治疗，n = 63）。比较两组疗效、尿动力学、外周血循环肿瘤细胞AR-V7、HoxB13水平以及生存预后。结果：观察组63例，对照组51例。治疗8周后，观察组疾病控制率与客观缓解率（分别为42.86%与96.83%）均显著高于对照组（分别为23.53%与86.27%）（P < 0.05）。观察组的最大尿流率[（14.58 ± 1.02）mL/s vs （11.18 ± 1.16）mL/s）]、平均尿流率[（12.92 ± 1.21）mL/s vs （9.83 ± 0.59）mL/s）]均显著高于对照组，而剩余尿量[（24.12 ± 1.96）mL vs （28.03 ± 1.68）mL）]显著低于对照组（均P < 0.05）。观察组与对照组的AR-V7 mRNA表达水平相近[（1.78 ± 0.32） vs （1.68 ± 0.46）]，差异无统计学意义（P > 0.05）；但观察组的HoxB13 mRNA表达水平显著低于对照组[（1.21 ± 0.27） vs （1.57 ± 0.37），P < 0.05]。观察组的中位无进展生存期[6.22个月（95%CI：5.63~6.63）]显著长于对照组[3.66个月（95%CI：3.01~3.74）]（P < 0.05）；观察组的3年总生存率为12.70%，显著高于对照组的0.00%（P < 0.05）。结论：地塞米松联合阿比特龙治疗CRPC患者具有显著疗效，能明显改善患者尿流动力，下调外周血循环肿瘤细胞中HoxB13的表达，未显著影响AR-V7的表达，还能延长患者PFS，提高3年总生存率。

Objective:To investigate the long-term outcome of deep brain stimulation (DBS) in patients with KMT2B gene-related dystonia. Methods:Seven patients with KMT2B gene-related dystonia who were treated at Peking Union Medical College Hospital from April 2018 to December 2020 were enrolled. Whole-exome sequencing was used to detect genetic variations, and clinical phenotypes were summarized. All patients underwent DBS surgery and were followed up at 6 months, 3 years, and 5 years post-surgery. The therapeutic effects of DBS were evaluated by Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), including BFMDRS Motor Subscale (BFMDRS-M) and Disability Subscale (BFMDRS-D). Results:The preoperative BFMDRS-M and BFMDRS-D scores were 60.43±27.12 and 17.00±6.24, respectively. The most significant improvements were observed at 6 months post-surgery, with the BFMDRS-M and BFMDRS-D scores being 20.64±5.50 and 9.57±1.72, reflecting improvements of 65.8% and 43.7%, respectively, both with statistically significant differences ( t=4.342, P=0.005; t=2.828, P=0.030). At 3 years post-surgery, the BFMDRS-M and BFMDRS-D scores were 26.20±8.68 and 10.50±2.74, representing improvements of 56.7% ( t=3.045, P=0.029) and 38.2% ( t=2.012, P=0.100), respectively. At 5 years post-surgery, the BFMDRS-M and BFMDRS-D scores were 27.80±14.87 and 11.00±2.83, with improvements of 54.0% ( t=1.824, P=0.142) and 35.3% ( t=1.933, P=0.125), respectively. At the 5-year postoperative follow-up, the patients′ cervical dystonia improved by 78.9%, while the upper limbs, lower limbs, and trunk dystonia improved by 57.8%, 56.6%, and 58.0%, respectively. However, only 1 patient showed significant improvement in the language function. Conclusions:DBS showed good therapeutic effects on KMT2B gene-related dystonia, but the efficacy declined over time. Significant improvements were observed in patients′ cervical, limb and trunk dystonia, but the improvement in language function was not significant.

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA