Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

Polyethylene terephthalate (PET) fibers are characterized by exceptional mechanical strength, and textiles blended with cotton fibers combine both comfort and durability, showcasing widespread use in daily applications. However, improper disposal of discarded polyester-cotton textiles has resulted in severe environmental pollution, necessitating urgent and effective mitigation strategies. Enzymatic recycling of textiles offers superior environmental benefits and holds greater potential for industrial applications than alternative recycling methods. This study aims to explore a large-scale solution for the treatment of waste textiles, particularly addressing the challenge of resource recovery from polyester-cotton blended fabrics. An innovative enzymatic depolymerization process has been developed to achieve the recovery of high-purity terephthalic acid monomers. Experiments were conducted on three different textile blends with polyester-to-cotton ratios of 65/35, 70/30, and 80/20, and the influences of different colors on the process were investigated. Initially, the textiles were pretreated through mechanical grinding, which was followed by depolymerization of cotton fibers with commercial cellulase. The crystallinity of PET in the textiles was reduced through a rapid heating and cooling process. Subsequently, the PET was depolymerized by the engineered PET hydrolase. The results demonstrated that after decolorization and separation of terephthalic acid (TPA) from the reaction system, the monomer recovery rates for the three textile blends (65/35, 70/30, and 80/20) reached 90%, 91%, and 92%, respectively. Characterization analysis by nuclear magnetic resonance (NMR) confirmed that the purity of the recovered TPA was greater than 99%. In conclusion, the fully enzymatic recycling process developed in this study shows considerable promise for large-scale industrial applications and is anticipated to significantly advance the adoption and development of enzymatic recycling technologies for PET in industrial processes.
Phthalic Acids/chemistry* ; Polyesters/chemistry* ; Textiles ; Cotton Fiber ; Polyethylene Terephthalates/chemistry* ; Cellulase/chemistry* ; Recycling/methods* ; Polymerization

Objective To investigate the mortality and risk factors of HIV-infected patients complicated with progressive multifocal leukoencephalopathy(PML)to inform the outcomes of these patients.Methods The clinical data of people living with HIV related PML who were treated at Chongqing Public Health Medical Treatment Center from January 1,2019 to December 31,2023 were retrospectively analyzed.Kaplan-Meier method was used for survival analysis.Log-rank test was performed.Cox regression model was used for multivariate analysis.Results A total of 42 people living with HIV related PML were enrolled,including 34 males(81.0％).The median age was 44.5(36.3,51.0)years.PML was confirmed in 76.2％(32/42)of patients,and possible PML was diagnosed in 23.8％(10/42)of patients.The median time to diagnosis was 32.5(14.8,58.3)days.The median CD4+T cell count was 69.0(39.8,112.0)cells/μL.The median HIV viral load was 5.05(2.62,5.77)log10 copies/mL.The overall mortality rate was 54.8％(23/42)for patients with HIV related PML.CD4+T cell count ≤50 cells/μL and initial modified Rankin scale(mRS)score ≥4 points were independent risk factors for the overall mortality of people living with HIV related PML(P＜0.05).Conclusions People living with HIV related PML have a high mortality rate.Low CD4+T cell count and high initial mRS score were independent risk factors for the mortality of patients with HIV related PML.Currently,no definitive and effective drug treatment is available for PML.Early detection,diagnosis and initiation of antiretroviral therapy may improve the outcomes of patients.

Background and purpose:Intrathecal chemotherapy is one of the mainstay treatment options for leptomeningeal metastases(LM)from solid tumors.A previous phase Ⅰ study demonstrated the safety and potential efficacy of intrathecal anti-programmed death receptor 1(anti-PD-1)for LM from melanoma.The synergistic efficacy of systemic chemotherapy combined with anti-PD-1 has been widely known.This study aimed to evaluate the safety and feasibility of intrathecal chemotherapy(pemetrexed)and anti-PD-1(toripalimab)for LM patients from solid tumors.Methods:The subjects were patients with LM from solid tumors who were treated at Affiliated Huizhou Hospital of Guangzhou Medical University/Third People's Hospital of Huizhou City.A 3+3 dose de-escalation strategy was implemented to determine the recommended dose with an initial dose of PD-1 inhibitor(toripalimab)40 mg and pemetrexed 15 mg.Pemetrexed was administered twice weekly for the initial 2 weeks of induction therapy,once weekly for the subsequent 4 weeks of consolidation therapy,and once monthly during maintenance therapy.PD-1 inhibitor was initiated at the 4th administration of pemetrexed,administered every 2 weeks for 6 weeks;subsequently,responders continued monthly maintenance therapy alongside pemetrexed.The primary objective was to assess safety based on adverse events and the recommended dose.All participants were observed to investigate the clinical response rate(CRR),disease control rate(DCR)and overall survival(OS).This study was approved by the ethics committee of Affiliated Huizhou Hospital of Guangzhou Medical University/Third People's Hospital of Huizhou City(ethics number:2024-KY-029-01).Results:Seven patients(male:3,female:4,median age:57 years)were enrolled between June and September 2024,including non-small cell lung cancer(6)and breast cancer(1).All patients presented with positive cerebrospinal fluid(CSF)cytology.Six patients presented LM-related neurological dysfunction.Five patients showed LM-related neuroimaging findings.Six patients completed the induction and consolidation therapy,and subsequently received maintenance therapy.One patient,due to bacterial meningitis,did not complete the final administration of toripalimab during consolidation therapy,and maintenance therapy was administered after infection control.Adverse events rate was 100%(7/7),including myelosuppression(100.00%,n=7),elevation of hepatic aminotransferases(42.86%,n=3),fatigue(28.57%,n=2)and hypothyroidism(14.29%,n=1).Three(42.86%)patients had grade 3 adverse events(myelosuppression).The immune-related adverse event(irAE)rate was 14.29%,manifested as hypothyroidism(Grade 2).No dose-limiting toxicity(DLT)was observed.Thus,no de-escalation was applied.The recommended dose was determined to be PD-1 inhibitor 40 mg in combination with pemetrexed 15 mg.Three patients showed improved neurological dysfunction,1 with CSF cytological response,and 2 with neuroimaging improvement.CRR was 57.14%(4/7)by response assessment in neuro-oncology(RANO)proposal criteria.DCR was 100%(7/7).Three patients exhibited abscopal effects with regression of brain metastasis lesions,primary lung lesion and mediastinal lymph nodes,respectively.As of April 10,2025,1 patient died.The median follow-up time was 7.7(5.9-9.3)months.The median OS was not reached with a 6-month OS rate of 85.71%.Conclusion:The combination therapy of intrathecal pemetrexed and a PD-1 inhibitor was well-tolerated and feasible,while also exhibiting potential clinical efficacy in treating LM from solid tumors including non-small cell lung cancer.

Objective To investigate the value of MRI of the sternal end of clavicle in bone age assessment in Chinese population,especially its applicability in the determination of criminal responsible age.Methods A total of 431 patients aged from 10.00 to 29.99 years with neck or chest MRI were retrospectively collected.According to the Schmeling grading method,the epiphyseal development of the clavicle MRI was divided into five grades.The consistency of methods was evaluated.The correlation and general descriptive analysis between MRI grades and age was analyzed.The sex difference was analyzed.Curve fitting was used to establish a nonlinear model between age and grades.Results The grades of clavicle MRI showed a significant age-related trend(Figure 2),and the correlation was 0.861(0.887 in males and 0.840 in females).Except for grade 1,there was no significant difference between males and females in other grades.The minimum age of male grade 3 was greater than 14 years old,and the minimum age of female grade 3 was greater than 16 years old.The minimum age in grade 4 and grade 5 was over 18 years old in both sexes.The best curve fitting model was cubic model for both sexes(R2=0.805 for men and 0.722 for women).Conclusion Clavicle MRI can be used for the assessment of bone age in Chinese population.Complete epiphyseal plate closure can be used as a reliable indicator for the determination of age at 18 years old,and it is expected to achieve radiation-free forensic bone age assessment.

Objective To investigate the mortality and risk factors of HIV-infected patients complicated with progressive multifocal leukoencephalopathy(PML)to inform the outcomes of these patients.Methods The clinical data of people living with HIV related PML who were treated at Chongqing Public Health Medical Treatment Center from January 1,2019 to December 31,2023 were retrospectively analyzed.Kaplan-Meier method was used for survival analysis.Log-rank test was performed.Cox regression model was used for multivariate analysis.Results A total of 42 people living with HIV related PML were enrolled,including 34 males(81.0％).The median age was 44.5(36.3,51.0)years.PML was confirmed in 76.2％(32/42)of patients,and possible PML was diagnosed in 23.8％(10/42)of patients.The median time to diagnosis was 32.5(14.8,58.3)days.The median CD4+T cell count was 69.0(39.8,112.0)cells/μL.The median HIV viral load was 5.05(2.62,5.77)log10 copies/mL.The overall mortality rate was 54.8％(23/42)for patients with HIV related PML.CD4+T cell count ≤50 cells/μL and initial modified Rankin scale(mRS)score ≥4 points were independent risk factors for the overall mortality of people living with HIV related PML(P＜0.05).Conclusions People living with HIV related PML have a high mortality rate.Low CD4+T cell count and high initial mRS score were independent risk factors for the mortality of patients with HIV related PML.Currently,no definitive and effective drug treatment is available for PML.Early detection,diagnosis and initiation of antiretroviral therapy may improve the outcomes of patients.

ObjectiveTo evaluate the clinical efficacy of different acupuncture-related therapies in treating postoperative pain in patients with osteoporotic vertebral compression fractures (OVCFs) after percutaneous kyphoplasty (PKP) or percutaneous vertebroplasty (PVP) using a network meta-analysis.MethodsA systematic search was conducted in PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database (SinoMed) from their inception to January 15, 2025. Outcome measures included the Visual Analog Scale (VAS) score, Oswestry Disability Index (ODI) score, and overall efficacy rate. Literature screening, data extraction, and risk-of-bias assessment were independently performed by two researchers. Data analysis was conducted using Stata 17.0 software.ResultsA total of 35 randomized controlled trials involving 2860 patients were included. The data analysis revealed that, in terms of improving VAS and ODI scores, the top three effective therapies were Fu's subcutaneous needling, wrist-ankle acupuncture, and acupotomy. For the overall efficacy rates in pain treatment, the top three therapies were wrist-ankle acupuncture, warm acupuncture and moxibustion, and Fu's subcutaneous needling. Based on the combined results across the three outcome measures, Fu's subcutaneous needling was found to be the most effective in relieving pain and improving lumbar function.ConclusionFu's subcutaneous needling, wrist-ankle acupuncture, warm acupuncture and moxibustion, and acupotomy were all effective in treating postoperative pain post-PKP/PVP and improving lumbar function. However, further high-quality, large-sample studies are required to confirm these findings.

ObjectiveTo explore the mechanism by which Buyang Huanwutang regulates the glutathione peroxidase 4 （GPX4）-acyl-CoA synthetase long-chain family member 4 （ACSL4） axis to inhibit ferroptosis and promote neurological functional recovery after spinal cord injury （SCI）. MethodsNinety rats were randomly divided into five groups： sham operation group， model group， low-dose Buyang Huanwutang group （12.5 g·kg^-1）， high-dose Buyang Huanwutang group （25 g·kg^-1）， and Buyang Huanwutang + inhibitor group （25 g·kg^-1 + 5 g·kg^-1 RSL3）. The SCI model was established by using the allen method. Tissue was collected on the 7th and 28th days after operation. Motor function was assessed by using the Basso-Beattie-Bresnahan （BBB） scale. Hematoxylin-eosin （HE）， Nissl， and Luxol fast blue （LFB） staining were performed to observe spinal cord histopathology. Transmission electron microscopy was used to examine mitochondrial ultrastructure. Immunofluorescence staining was used to detect the number of NeuN-positive cells and the fluorescence intensity of myelin basic protein （MBP）， GPX4， and ACSL4. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） was used to analyze the mRNA expression of GPX4 and ACSL4. Enzyme linked immunosorbent assay （ELISA） was performed to measure the levels of reactive oxygen species （ROS）， malondialdehyde （MDA）， glutathione （GSH）， and superoxide dismutase （SOD）. Colorimetric assays were used to determine the iron content in spinal cord tissue. ResultsCompared to the sham operation group， the model group exhibited significantly reduced BBB scores （P<0.01）， severe pathological damage in spinal cord tissue， and marked mitochondrial ultrastructural disruption. In addition， the model group showed a decrease in the number of NeuN-positive cells （P<0.01）， reduced fluorescence intensity of MBP and GPX4 （P<0.01）， lower levels of GSH and SOD （P<0.01）， and downregulated mRNA expression of GPX4 （P<0.01）. Moreover， compared to the sham operation group， the model group had elevated levels of ROS， MDA， and tissue iron content （P<0.01）， along with increased fluorescence intensity and mRNA expression of ACSL4 （P<0.01）. Compared with the model group and Buyang Huanwutang + inhibitor group， the Buyang Huanwutang group showed significantly improved BBB scores （P<0.05， P<0.01） and exhibited less severe spinal cord tissue damage， reduced edema and inflammatory cell infiltration， increased neuronal survival， and more intact myelin structures. Additionally， mitochondrial ultrastructure was significantly improved in the Buyang Huanwutang group. Compared to the model group and Buyang Huanwutang + inhibitor group， the Buyang Huanwutang group significantly increased the number of NeuN-positive cells and the fluorescence intensity of MBP （P<0.05， P<0.01）. Furthermore， Buyang Huanwutang significantly increased the fluorescence intensity and mRNA expression of GPX4 （P<0.01） and decreased the fluorescence intensity and mRNA expression of ACSL4 （P<0.01） compared to the model group and Buyang Huanwutang + inhibitor group. Finally， the Buyang Huanwutang group significantly decreased ROS， MDA， and tissue iron content （P<0.01） and significantly increased GSH and SOD levels （P<0.01） compared to the model group and Buyang Huanwutang + inhibitor group. ConclusionBuyang Huanwutang inhibits ferroptosis through the GPX4/ACSL4 axis， reduces secondary neuronal and myelin injury and oxidative stress， and ultimately promotes the recovery of neurological function.

Objective To investigate the prevalence and influencing factors of thyroid enlargement in school-age children in Tianjin. Methods School-age children were randomly selected in Tianjin to undergo thyroid ultrasound examination, and salt iodine, urine iodine, height, and weight tests. A questionnaire survey was conducted. Univariate and multivariate regression models were used to analyze the risk factors for thyroid enlargement. Results A total of 917 children aged 7-13 years in Tianjin were surveyed, with a thyroid enlargement rate of 4.03% and a median thyroid volume of 2.60 ml. There was a non-linear relationship between children's body mass index (BMI) and the incidence of thyroid enlargement in children (P=0.008), and a linear relationship between children's body surface area (BSA) and the incidence of thyroid enlargement in children (P<0.001). Being 9 years old (OR=3.728, 95%CI: 1.343-10.343, P=0.012), obesity (OR=3.886, 95%CI: 1.801-8.384, P=0.001), having lunch at school (OR=3.157, 95%CI: 1.497-6.658, P=0.003) and frequent consumption of preserved foods (OR=4.611, 95%CI: 1.643-12.945, P=0.004) were risk factors for goiter in children. Regular consumption of seaweed (OR=0.305, 95%CI: 0.100-0.927, P=0.036) was a protective factor for goiter in children. Conclusion The incidence of thyroid enlargement in children in Tianjin meets national standards. Obesity, eating lunch at school, frequently consuming pickled foods, and being 9 years old may be risk factors for thyroid enlargement in children. Eating seaweed or kelp regularly is a protective factor. At the same time, attention should be paid to the relationship between BMI, BSA, and thyroid enlargement rate in children..

Objective To explore the association between different levels of fluoride exposure and dyslipidemia in elderly people, and to analyze the influencing factors and their interactions. Methods A total of 1 143 elderly people over 60 years old were randomly selected from historical high water fluorosis areas and control areas in Tianjin. Logistic regression model and classification tree model were used to analyze the influencing factors of dyslipidemia, and to analyze the interaction between high fluoride exposure and relevant influencing factors on dyslipidemia. Results The prevalence of elevated low density lipoprotein cholesterol (LDL-C) was 5.69% (65/1 143). There was a significant difference in the prevalence of high LDL-C in different fluoride-exposed areas (2 = 0.092，P = 0.762). Multivariate logistic analysis showed that high fluoride exposure (OR=2.306，95%CI：1.185-4.491) and abdominal obesity (OR=2.274，95%CI：1.299-3.978) were risk factors for high LDL-C, while type B personality (OR=0.529，95%CI：0.308-0.908) was a protective factor for high LDL-C. The results of classification tree model showed that abdominal obesity contributed the most to the prevalence of high LDL-C in the elderly, followed by high fluoride exposure and hyperglycemia. There was a significant multiplicative interaction between high fluoride exposure and abdominal obesity on dyslipidemia (OR=5.191,95%CI：1.609-16.745，P=0.006). Conclusion High fluoride exposure may increase the risk of high LDL-C, and there is a multiplicative interaction between high fluoride exposure and abdominal obesity on dyslipidemia.