Objective To investigate the expression characteristics and clinical significance of endothelial cell-derived extracellular vesicles(EC-EVs)in the peripheral blood of patients with sep-sis-induced cardiomyopathy(SIC).Methods A total of 143 sepsis patients were enrolled and divid-ed into cardiomyopathy group(n=72)and non-cardiomyopathy group(n=71)based on occurrence of SIC.Peripheral blood samples were collected from patients in both groups upon admission for isola-tion and identification of EC-EVs.The number of EC-EVs,apoptosis,and the activity and expression levels of caspase-1 in EC-EVs were compared between the two groups.Spearman correlation analysis was used to assess the correlations of the number of EC-EVs,caspase-1 activity,and N-terminal pro-brain natriuretic peptide(NT-proBNP)with cardiac troponin Ⅰ(cTnⅠ).Multivariable Logistic regres-sion analysis was conducted to explore the factors influencing the occurrence of SIC in sepsis patients.Receiver operating characteristic(ROC)curves were plotted to analyze the predictive value of the number of EC-EVs and caspase-1 activity for SIC.Results EC-EVs with a diameter of approximately 100 nm,intact membrane structure,and expression of extracellular vesicles(EVs)marker molecules(CD9,CD63,CD81)were successfully isolated from samples in both groups.The cardiomyopathy group had significantly higher numbers of EC-EVs in peripheral blood,EC-EV apoptosis levels,caspase-1 activity,and protein expression levels compared to the non-cardiomyopathy group(P＜0.05).Spearman correlation analysis revealed positive correlations between the number of EC-EVs and NT-proBNP(r=0.603,0.685,P＜0.001),and between caspase-1 activity and cTnⅠ(r=0.474,0.711,P＜0.001).Multivariable Logistic regression analysis showed that the number of EC-EVs,caspase-1 activity,NT-proBNP levels,and cTnⅠ levels were all independent influencing factors for the occurrence of SIC in sepsis patients(P＜0.05).The ROC curves indicated that the areas under the curve for predicting SIC based on the number of EC-EVs and caspase-1 activity in peripheral blood were 0.721 and 0.858,respectively.Conclusion The number of EC-EVs and caspase-1 activity in EC-EVs in the peripheral blood of SIC patients are significantly increased,and are closely related to cardiac function and myocardial injury in sepsis patients.Thus,they have the potential to become biomarkers for predicting SIC.

Objective: To investigate the detection of natural infection with pathogens in rodents in Huzhou City, Zhejiang Province, so as to provide a basis for risk assessment and control of rodent-borne diseases. Methods: From August to September each year during the period of 2022-2024, urban residential areas, rural residential areas, key industries, farmland and cultivated land, forests, and shrublands in various counties (districts) of Huzhou City were selected as rodent surveillance sites. Rodents were captured using the trap night method. Following anesthesia, the rodents were euthanized by cervical dislocation. Species were identified based on morphological characteristics. Under sterile conditions, dissection was performed to collect liver, spleen, lung, and kidney tissues. These tissues were then mixed together, and detected for Hantavirus, Dabie bandavirus, Leptospira, and Orientia tsutsugamushi using fluorescence quantitative PCR. The detection rates of these natural infections with pathogens were analyzed across different rodent species, counties (districts), and habitats. Results: A total of 259 rodents were captured from 2022 to 2024, including Rattus norvegicus, Rattus tanezumi, Suncus murinus, Mus musculus, Leopoldamys edwardsi, Niviventer fulvescens, Rattus losea, and Apodemus agrarius. The dominant species were Rattus norvegicus (142 individuals) and Rattus tanezumi (59 individuals), collectively accounting for 77.61%. With the exception of Orientia tsutsugamushi, Hantavirus, Dabie bandavirus, and Leptospira were all detected, with detection rates of 5.02%, 1.93%, and 10.42%, respectively. Hantavirus and Leptospira were simultaneously detected in one Rattus norvegicus, yielding a mixed infection rate of 0.39%. The three pathogens were detected in rodents in Wuxing District, Nanxun District, Deqing County, Changxing County, and Anji County, with detection rates of 6.45%, 5.71%, 26.32%, 4.76%, and 24.00%, respectively. They were also detected in rodents in urban residential areas, rural residential areas, key industries, farmland, and forests, with detection rates of 28.57%, 21.57%, 10.91%, 12.50%, and 14.81%, respectively. Notably, all three pathogens were simultaneously detected in Rattus norvegicus, Rattus tanezumi, rural residential areas, and key industries. Conclusions Rattus norvegicus and Rattus tanezumi were identified as the dominant rodent species in Huzhou City. The detection of Hantavirus, Dabie bandavirus, and Leptospira, including instances of mixed infection. It is necessary to enhance surveillance and control measures targeting these key species and high-risk habitats.

Objective To investigate the association between cerebrospinal fluid(CSF)oligoclonal band(OCB)positivity and clinical manifestations in patients with neuromyelitis optica spectrum disorder(NMOSD).Methods A retrospective analysis of clinical data from patients with NMOSD treated at our hospital from May 2019 to January 2024 was conducted.Based on OCB test results,patients were categorized into OCB-positive and OCB-negative groups.We compared baseline characteristics between the two groups and analyzed the relationship between clinical features and OCB positivity.Results This study included a total of 62 patients,comprising 17 in the OCB+group and 45 in the OCB-group.Compared with the OCB-group,patients in the OCB+group exhibited more pronounced central nervous system inflammatory features.Specifically,OCB+group had significantly higher proportions of patients with cerebrospinal fluid white blood cell counts>8×10?/L(64.7%vs.26.7%,P=0.003)and elevated immunoglobulin indices(0.72 vs.0.61,P=0.037).Additionally,the OCB+group exhibited more complex and diverse clinical presentations.Specifically,this group showed a higher incidence of mild consciousness impairment during the acute phase(P=0.005)and a greater tendency to present with multiple core symptoms(≥3 core symptoms)occurring concurrently(52.9%vs.20.0%,P=0.025)and misdiagnosis(29.4%vs.8.9%,P=0.101).This was particularly notable when comparing to acute myelitis involving the cervical spinal cord(82.4%vs.53.3%,P=0.036)and acute diencephalic syndrome[41.2%vs.6.7%,P=0.004,including hyponatremia(35.3%vs.8.9%,P=0.033)].Multivariate logistic regression analysis demonstrated that OCB positivity(OR=3.895,95%CI:1.065-14.249)was significantly associated with the presence of multiple core symptoms.Conclusion In acute-phase NMOSD patients,OCB+is associated with significantly higher rates of co-occurrence of multiple core symptoms(≥3 core symptoms)and misdiagnosis.Notably,acute myelitis involving the cervical spinal cord and acute diencephalic clinical syndrome are particularly prevalent in this OCB+subgroup.The clinical manifestations are complex and diverse,suggesting the need for enhanced clinical identification and timely intervention.

Objective To investigate the association between cerebrospinal fluid(CSF)oligoclonal band(OCB)positivity and clinical manifestations in patients with neuromyelitis optica spectrum disorder(NMOSD).Methods A retrospective analysis of clinical data from patients with NMOSD treated at our hospital from May 2019 to January 2024 was conducted.Based on OCB test results,patients were categorized into OCB-positive and OCB-negative groups.We compared baseline characteristics between the two groups and analyzed the relationship between clinical features and OCB positivity.Results This study included a total of 62 patients,comprising 17 in the OCB+group and 45 in the OCB-group.Compared with the OCB-group,patients in the OCB+group exhibited more pronounced central nervous system inflammatory features.Specifically,OCB+group had significantly higher proportions of patients with cerebrospinal fluid white blood cell counts>8×10?/L(64.7%vs.26.7%,P=0.003)and elevated immunoglobulin indices(0.72 vs.0.61,P=0.037).Additionally,the OCB+group exhibited more complex and diverse clinical presentations.Specifically,this group showed a higher incidence of mild consciousness impairment during the acute phase(P=0.005)and a greater tendency to present with multiple core symptoms(≥3 core symptoms)occurring concurrently(52.9%vs.20.0%,P=0.025)and misdiagnosis(29.4%vs.8.9%,P=0.101).This was particularly notable when comparing to acute myelitis involving the cervical spinal cord(82.4%vs.53.3%,P=0.036)and acute diencephalic syndrome[41.2%vs.6.7%,P=0.004,including hyponatremia(35.3%vs.8.9%,P=0.033)].Multivariate logistic regression analysis demonstrated that OCB positivity(OR=3.895,95%CI:1.065-14.249)was significantly associated with the presence of multiple core symptoms.Conclusion In acute-phase NMOSD patients,OCB+is associated with significantly higher rates of co-occurrence of multiple core symptoms(≥3 core symptoms)and misdiagnosis.Notably,acute myelitis involving the cervical spinal cord and acute diencephalic clinical syndrome are particularly prevalent in this OCB+subgroup.The clinical manifestations are complex and diverse,suggesting the need for enhanced clinical identification and timely intervention.

BACKGROUND:Titanium and its alloys are widely used in orthopedic implants due to their excellent biocompatibility,corrosion resistance,and mechanical properties.However,it has biological inertia itself,cannot provide a good growth environment for osteoblasts,and it is difficult to form good osseointegration. OBJECTIVE:To construct a composite hydrogel material of gelatin methacryloyl and polyacrylamide on the surface of titanium alloy scaffold,and analyze its osteogenic ability in vitro. METHODS:Gelatin methacryloyl was mixed with acrylamide.Crosslinking agent and catalyst were added to synthesize gelatin methacryloyl and acrylamide(Gelma-PAAM)composite hydrogel.The titanium alloy scaffold modified by affinity silane was mixed with the Gelma hydrogel and Gelma-PAAM composite hydrogel to complete the loading(recorded as Ti-Gelma and Ti-Gelma-PAAM,respectively).The swelling ratio and degradation rate of the two hydrogels on the surface of the scaffold were compared.The bonding state between hydrogels and titanium alloy was observed by scanning electron microscope.Rat bone marrow mesenchymal stem cells were inoculated into Ti,Ti-Gelma and Ti-Gelma-PAAM scaffolds,separately.Cell proliferation,adhesion,and osteogenic differentiation were detected. RESULTS AND CONCLUSION:(1)Compared with Gelma hydrogel,Gelma-PAAM hydrogel had higher swelling rate and lower degradation rate.(2)Scanning electron microscope showed that the surface of the two kinds of hydrogels was honeycomb structure.After being combined with porous titanium alloy scaffold,the film was wrapped on the surface of scaffold and filled with pores.Among them,the Gelma-PAAM composite hydrogel coated the scaffold more fully.(3)CCK-8 assay and live/dead fluorescence staining showed that bone marrow mesenchymal stem cells proliferated well after coculture with Ti-Gelma and Ti-Gelma-PAAM scaffolds and maintained high activity.After osteogenic induction culture,alkaline phosphatase activity,calcium deposition,and osteogenic gene expression of cells of titanium alloy scaffold group were the lowest,and alkaline phosphatase activity,calcium deposition,and osteogenic gene expression of cells of Ti-Gelma-PAAM scaffold group were the highest.(4)Phalloidin cytoskeletal staining exhibited that the cells of pure titanium alloy scaffold group and Ti-Gelma scaffold group were sparse and insufficiently extended,while the cells of Ti-Gelatin-PAAM group had the most adequate stretching and the densest filamentous actin.(5)The results show that Gelma-PAAM hydrogel has good biocompatibility and osteogenic ability,and is more suitable for osteogenic modification on the surface of titanium alloy than Gelma hydrogel.

BACKGROUND:The low catalytic activity and lack of targeting of commonly used metal ions have severely limited the clinical application of chemodynamic therapy in tumor treatment.On the other hand,although the composite nanoplatforms are endowed with tumor-targeting functions by surface functionalization,the lack of tumor microenvironment acidity also severely weakens the efficacy of chemodynamic therapy. OBJECTIVE:To prepare novel composite nanoplatforms and assess their feasibility to enhance the effects of chemodynamic therapy at the cellular level. METHODS:SLC-0111-loaded zeolite imidazole framework-8 doped with divalent iron ions(Fe2+)and divalent cobalt ions(Co2+)(Fe-Co/ZIF-8@SLC-0111)was synthesized by ion-exchange reaction and self-assembly,and loaded with hyaluronic acid(HA)by electrostatic adsorption,followed by obtaining the target nanoparticles Fe-Co/ZIF-8@SLC-0111-HA(abbreviated as FC-S).Meanwhile,nanoparticles Fe-Co/ZIF-8-HA(abbreviated as FC)without SLC-0111 were synthesized by the same method.The nanocomposite platform was tested for particle size,zeta potential,surface morphology,in vitro reactive oxygen species generation,and ability to consume glutathione.Human osteosarcoma cell MG-63 and mouse fibroblast cell L929 were used as experimental subjects.The cytotoxicity of FC-S was detected by CCK-8 assay.Human osteosarcoma cell MG-63 was used as the experimental object to detect the cell internalization of FC-S.In addition to H2O2,the effects of FC-S and FC on intracellular pH,carbonic anhydrase 9 protein expression,cell viability and apoptosis,intracellular reactive oxygen species and glutathione content,and mitochondrial membrane potential were investigated. RESULTS AND CONCLUSION:(1)The FC-S composite nanoplatform was successfully prepared with a well-defined rhombic dodecahedral structure,uniform size and good dispersion.Its particle size was about 323 nm;zeta potential was about-11.1 mV,and the nanoplatform had a certain reactive oxygen species generation capacity in vitro.(2)FC-S nanoplatforms accumulated intracellularly in a time-dependent manner and could successfully escape from lysosomes.When the mass concentration of FC-S was≤20 μg/mL,there was no obvious cytotoxicity to MG-63 cells and L929 cells,and 20 μg/mL FC-S was selected to act on MG-63 cells in subsequent experiments.(3)Compared with FC group,the protein expression of carbonic anhydrase 9 in MG-63 cells in FC-S group was decreased(P<0.01);the intracellular acidic environment was enhanced;the content of reactive oxygen species was increased(P<0.001);the mitochondrial damage was aggravated;the number of dead cells was increased,and the apoptosis rate was increased(P<0.001).(4)The results indicate that FC-S,as a novel composite nanoplatform,can effectively improve the weakly acidic microenvironment in tumor cells and enhance the level of intracellular reactive oxygen species production,thus enhancing the efficacy of chemodynamic therapy.

Background and purpose:DDX is an adenosine triphosphate(ATP)-dependent RNA helicase closely related to mRNA regulation,tumor proliferation and invasion.This article aimed to explore the effect of DDX6,a member of the DDX family,on the stability of CKMT1A mRNA,as well as the effect of the DDX6 CKMT1A axis on the proliferation and migration ability of human nasopharyngeal carcinoma cell CNE2 and its molecular mechanism.Methods:We retrieved the data of expressions of DDX6 and CKMT1A in human head and neck squamous cell carcinoma from The Cancer Genome Atlas(TCGA)database and performed a correlation analysis.Western blot was performed to detect the expressions of CKMT1A and DDX6 in human nasopharyngeal carcinoma tissues and normal nasopharyngeal tissues preserved by Affiliated Hospital of Nantong University.This study was approved by the Ethics Committee of Affiliated Hospital of Nantong University(Number:2022-L114).We used transwell assay to detect cell migration ability,EdU assay to detect cell proliferation ability,and colony formation assay to detect clone formation ability.We transfect with lentivirus and plasmids to construct sh-DDX6,sh-CKMT1A,sh-CKMT1A+sh-DDX6 and oe-CKMT1A cell models derived from the human nasopharyngeal carcinoma cell line CNE2,preserved by Affiliated Hospital of Nantong University,to clarify the impact of DDX6 and CKMT1A expression levels on the malignant biological phenotypes of nasopharyngeal carcinoma cells.BALB/c nude mice subcutaneous xenograft tumor model was constructed to detect the effects of DDX6 and CKMT1A on nasopharyngeal carcinoma cells in mice.RNA stability assay was used to detect the effect of DDX6 knockout on CKMT1A mRNA and further clarify the molecular mechanism of DDX6.Results:DDX6 was highly expressed,CKMT1A level was low in human nasopharyngeal carcinoma tissue,and DDX6 was negatively correlated with CKMT1A expression.DDX6 inhibited protein translation of CKMT1A by disrupting its mRNA stability.Low expression of CKMT1A in CNE2 cells enhanced cell migration and proliferation ability,while high expression inhibited migration and proliferation ability.Knocking out DDX6 reversed the progression of malignant behavior caused by downregulation of CKMT1A.Low expression of CKMT1A promoted tumor cell growth in BALB/c nude mice subcutaneous xenograft tumor model,while low expression of DDX6 inhibited tumor cell growth.Knocking out DDX6 and CKMT1A simultaneously restored the inhibitory effect caused by knocking down DDX6 alone.Conclusion:DDX6 in nasopharyngeal carcinoma cells disrupts the stability of CKMT1A mRNA,negatively regulates CKMT1A protein translation,upregulates the proliferation and migration ability of nasopharyngeal carcinoma cells,and promotes malignant progression of nasopharyngeal carcinoma.

Objective:To investigate the iodine nutrition levels of children aged 8 - 10 and pregnant women in iodine deficient areas and iodine adequate areas of Inner Mongolia Autonomous Region (Inner Mongolia for short), and to provide scientific basis for prevention and treatment of iodine deficiency disorders.Methods:From March to July 2022, iodine nutrition analysis was conducted in iodine deficient areas and iodine adequate areas of 104 banners (counties, cities and districts) in 12 league cities in Inner Mongolia. Each monitoring banner (county, city and district) was divided into five sampling areas by east, west, south, north, and center, with one Sumu (township, street) selected from each area. One primary school was selected from each Sumu (township, street), and 40 non-boarding students aged 8 - 10 were selected from each primary school. One third of the students underwent thyroid ultrasound examination. Twenty pregnant women were selected from each of the 5 Sumus (townships, streets) in each monitoring banner (county, city and district). Household salt samples and random urine samples of children and pregnant women were collected to detect salt iodine and urinary iodine levels.Results:In 2022, the median thyroid volume of children aged 8 - 10 in iodine deficient areas and iodine adequate areas of Inner Mongolia was 2.44 ml, and the goiter rate was 1.89% (123/6 496). There were statistically significant differences in thyroid volume and goiter rate between different league cities ( H = 1 229.05, χ 2 = 34.13, P < 0.001). The coverage rate of iodized salt in 12 league cities was 98.51% (30 628/31 090), the consumption rate of qualified iodized salt was 94.42% (29 355/31 090), and the median salt iodine was 22.80 mg/kg. The median urinary iodine of children ( n = 20 968) was 195.00 μg/L, among which the median urinary iodine in 7 league cities was at the appropriate level of iodine nutrition (100 - 199 μg/L), and the median urinary iodine in 5 league cities was at the level of iodine nutrition exceeding the appropriate level (200 - 299 μg/L). The median urinary iodine of pregnant women ( n = 10 122) was 168.00 μg/L, among which, except for Bayannur (149.18 μg/L), the median urinary iodine in other 11 league cities was at the appropriate level of iodine nutrition (150 - 249 μg/L). Conclusions:The overall iodine nutrition of children and pregnant women in Inner Mongolia is at an appropriate level, but some pregnant women still face the risk of iodine deficiency. In the future, the focus of iodine deficiency disorders prevention and control should be on iodine nutrition monitoring for special needs populations.

Purpose: The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti–programmed cell death-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT. Materials and Methods: This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child-Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles. Results: During a median follow-up of 11.23 months (range, 3.07 to 34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The 2-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively. Conclusion Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.

Objective:To study the iodine nutrition status of children in non-high water iodine areas of Inner Mongolia Autonomous Region, analyze the monitoring results of iodine deficiency disorders, so as to provide a basis for further guidance on scientific iodine supplementation for children in Inner Mongolia Autonomous Region.Methods:According to the requirements of the National IDD Monitoring Program and the IDD Monitoring Program of Inner Mongolia in 2021, cluster sampling method was used to select non boarding children aged 8 - 10 from 104 counties (cities, districts) in 12 cities within the jurisdiction of Inner Mongolia Autonomous Region. Random urine samples and household salt samples were collected to detect iodine content. At the same time, 1/3 of the selected children were selected for thyroid B-ultrasound examination to measure thyroid volume.Results:In 2021, a total of 19 968 children aged 8 - 10 in non-high water iodine areas of Inner Mongolia were monitored, and 19 968 urine samples were collected, with a median urine iodine of 199.23 μg/L. There was a statistically significant difference in the frequency distribution of urinary iodine in different cities (χ 2 = 839.51, P < 0.001). The median iodine content of children's household edible salt was 22.64 mg/kg, and the coverage rate of iodized salt, qualified iodized salt coverage rate, and non-iodized salt rate in the entire region was 99.05% (19 778/19 968), 94.98% (18 785/19 778), 94.08% (18 785/19 968) and 0.95% (190/19 968), respectively. Thyroid B-ultrasound were performed in 6553 children, the goiter rate was 1.30% (85/6 553), and there were statistically significant differences in goiter rates among children of different ages and cities (χ 2 = 87.09, P < 0.001; χ 2 = 10.40, P = 0.006) . Conclusions:In 2021, the iodine nutrition of children aged 8 - 10 in non-high water iodine areas of Inner Mongolia is at an appropriate level. However, in the future we should continue to adhere to the monitoring of iodine deficiency disorders, strengthen health education on iodine deficiency disorders, consolidate existing achievements in iodine deficiency disease prevention and control, and achieve the goal of continuous elimination of iodine deficiency disorders.