BACKGROUND:In the repair of large bone defects,a variety of factors such as seed cell passaging can cause senescence of osteoblasts,leading to a reduction in osteogenic differentiation activity after implantation of tissue-engineered bone.In recent years,a novel mechanism involving primary cilia in cell senescence has been widely studied,but the primary cilia-related mechanism of"passage senescence-reduced osteogenic activity"is not fully understood.OBJECTIVE:To explore the possible mechanisms by which primary cilia regulate the senescence of MC3T3-E1 cells.METHODS:The osteoblast precursor cell lines MC3T3-E1 were passaged to 10th generation cells(early passage)and 40th generation cells(late passage).siRNA was used to silence IFT88 to inhibit primary cilia formation.The cells were than grouped into passage 10 group,passage 40 group,passage 10+siRNA IFT88 group,and passage 40+siRNA IFT88 group.RT-PCR and western blot assays were used to detect the expression of the aging marker P16(CDKN2A),the osteogenic activity markers bone morphogenetic protein 2 and alkaline phosphatase,and the Hedgehog pathway IHH expression.Alizarin red staining and primary cilia immunofluorescence staining were performed.Spearman correlation analysis was conducted to analyze primary cilia positive rate and IHH and bone morphogenetic protein 2 expression.RESULTS AND CONCLUSION:(1)The expression of CDKN2A(P16)in the passage 10 group was significantly higher than in the passage 40 group,but the difference disappeared after siRNA IFT88 intervention.(2)Meanwhile,the positive rate of primary cilia cells in the passage 10 group were higher than in the passage 40 group,while siRNA IFT88-significantly inhibited the expression of primary cilia in both passage 10 and passage 40 cells.(3)The transcriptional activity and protein expression of bone morphogenetic protein 2 and alkaline phosphatase in the passage 10 group were higher than those in the passage 40 group.After inhibiting the expression of primary cilia with siRNA,the above differences were reduced or disappeared.(4)The positive rate of primary cilia cells was correlated with IHH and bone morphogenetic protein 2 protein expression.To conclude,primary cilia mediate the replicative senescence of osteogenic MC3T3-E1 cells and regulate osteogenic differentiation ability.

Mitochondrial diabetes mellitus(MDM)is a genetically heterogeneous disorder caused by mitochondrial DNA(mtDNA)or nuclear DNA mutations,characterized by multi-system involvement and diverse clinical phenotypes.We report a pediatric case presenting with growth retardation followed by subsequent development of diabetes mellitus.Systematic evaluation revealed concurrent bilateral sensorineural hearing loss,bilateral basal ganglia calcification,and electroencephalographic abnormalities.A post-exercise lactate test demonstrated significant elevation of serum lactate levels immediately after physical exertion.Genetic analysis identified a large-scale mitochondrial DNA deletion spanning from m.8649 to m.16084.This case re-port is complemented by a literature review focusing on the pathogenesis,genetic characteristics,and therapeu-tic approaches of mitochondrial diabetes,with particular emphasis on mitochondrial disorders exhibiting large-scale mtDNA deletions alongside diabetic manifestations.Our comprehensive analysis aims to enhance clinical understanding and inform diagnostic strategies for this complex disease entity.

Objective:To investigate the clinical predictive value of Ki67 proliferation index combined with preoperative serum Ctn for postoperative biochemical cure of medullary thyroid carcinoma (MTC) .Methods:Clinical data were collected from Dec. 2008 to Dec. 2024 from 90 patients with surgically confirmed MTC at China-Japan Union Hospital of Jilin University. The optimal cut-off value for preoperative Ctn prediction of biochemical cure (171.18pg/mL) was determined by the ROC curve; the Ki67 proliferation index cut-off value was adopted from the international MTC grading system standard (5%). Patients were divided into three groups based on the above cutoff values: double-low group (Ki67 <5% and Ctn <171.18pg/mL, n=23), single-high group (Ki67 ≥5% and Ctn <171.18pg/mL or Ki67 <5% and Ctn ≥171.18pg/mL, n=49), and double-high group (Ki67 ≥5% and Ctn ≥171.18pg/mL, n=18). The Kaplan-Meier method (Log-Rank and Trend test) was used to compare the differences in biochemical cure rates between groups, and the Cox proportional risk model was used to analyze the risk factors affecting biochemical cure. Results:The correlation between preoperative Ctn and Ki67 proliferation index was not significant. The three groups differed significantly in gender, tumor distribution, tumor size, vascular invasion, N stage, TNM stage, and biochemical cure ( P<0.05), with the double-high group being significantly associated with larger tumors, later N stage and TNM stage, and lower biochemical cure ( P<0.001). Kaplan-Meier analysis showed that the biochemical cure rate in the double-high, single-high, and double-low groups showed a stepwise improvement.Cox univariate analysis showed that tumor size, N stage, TNM stage, preoperative Ctn, and Ki67 combined with Ctn were risk factors for failure to biochemically cure; multivariate analysis confirmed that the double-high group was an independent risk factor ( P<0.05). In the single-high group, the biochemical cure rate of patients in the low Ki67-high Ctn group was lower than that of the high Ki67-low Ctn group and more malignant. Ki67 had less effect on biochemical cure and disease-free survival at the low Ctn level, and Ki67 was an independent risk factor for failure to biochemically cure at the high Ctn level ( P=0.023) and was significantly associated with disease-free survival ( P=0.004) . Conclusions:Serum Ctn is more sensitive than Ki67 index in predicting biochemical cure after MTC, and the correlation between the two was weak. Ki67 proliferation index alone has limited prognostic value, but combines with preoperative Ctn significantly optimize the prognostic assessment of patients.The role of Ki67 index varied at different Ctn levels.

Objective: To investigate the awareness of knowledge about hepatitis C prevention and control among outpatients in Ningbo City, Zhejiang Province, and its influencing factors, so as to provide the evidence for strengthening health education on hepatitis C prevention and control. Methods: Based on sentinel surveillance of hepatitis C, the outpatients aged 15 to 65 years at seven hospitals in Yinzhou District, Cixi City and Xiangshan County of Ningbo City were selected using the convenient sampling method from April to June during 2020 and 2022. Demographic information, knowledge and behaviors related to hepatitis C prevention and control were collected through questionnaire surveys. The influencing factors for knowledge about hepatitis C prevention and control were analyzed using a multivariable logistic regression model. Results: A total of 2 792 participants were surveyed, including 1 157 males (41.44%) and 1 635 females (58.56%). The awareness rate of knowledge about hepatitis C prevention and control was 56.23%, and was lower in knowledge about hepatitis C vaccine and treatment. The awareness rates of knowledge about hepatitis C prevention and control among outpatients from 2020 to 2022 were 47.11%, 53.22% and 70.65%, respectively, showing an upward trend (P<0.05). Multivariable logistic regression analysis showed that participants aged 25 to <50 years (OR=1.358, 95%CI: 1.073-1.719), with an educational level of high school or junior college (OR=1.431, 95%CI: 1.134-1.806) or above junior college (OR=3.728, 95%CI: 2.958-4.699), with household monthly income per capita of 3 000 to <5 000 yuan (OR=1.828, 95%CI: 1.344-2.486) or ≥5 000 yuan (OR=1.858, 95%CI: 1.366-2.526), without a history of invasive treatments such as pedicure in public places (OR=1.287, 95%CI: 1.024-1.618), without a history of contact with family members' blood-contaminated items (OR=2.050, 95%CI: 1.552-2.707), and always using condoms during sexual contacts (OR=1.740, 95%CI: 1.273-2.378) had higher awareness of knowledge about hepatitis C prevention and control. Conclusions The awareness of knowledge about hepatitis C vaccine and treatment among outpatients in Ningbo City needs to be improved. Age, educational level, household monthly income per capita, history of invasive treatments such as pedicure in public places, history of contact with family members' blood-contaminated items and frequency of condom use during sexual contacts are associated with outpatients' awareness of knowledge about hepatitis C prevention and control.

Objective To investigate the clinical characteristics in an elderly patient with sellar multiple myeloma.Methods Clinical features,laboratory data and radiologic profile of an elderly patient with sellar multiple myeloma were collected.Results The patient was an 85-year-old male.The main clinical manifestations were fatigue,poor appetite and polyuria.Laboratory examinations showed a significant decrease in blood sodium,several anterior pitu-itary hormones and an increase in total protein,mass of pituitary lesion and concentration of prolactin.During etio-logical screening,it was found that the blood immunoglobulin G(IgG)level was significantly increased,the blood M protein was positive and the bone marrow smear showed myeloma cells accompanied by multiple osteolytic lesions in the bones of the whole body.Considering the diagnosis of multiple myeloma,the pituitary lesion was likely to be the extra-medullary involvement.Conclusions The intrasellar plasmacytoma is not common.The disease onset is insidious with clinical features and imaging findings lacking specificity.Therefore,diagnosis relies on biopsy which poses risks for elderly patients and increases diagnostic challenges leading to misdiagnosis.

Objective:Efficacy of prothrombin complex concentration (PCC) and analysis of prognostic factors in patients with traumatic trauma-induced coagulopathy (TIC).Methods:A retrospective study was conducted on patients with TIC admitted to 11 hospitals from January to December 2021. The data included baseline characteristics, injury information, blood product transfusions (including PCC treatment), laboratory examination at admission and 24 hour-after admission, treatment measure, pre-hospitalization time, and clinical outcomes (improvement at discharge, length of hospital stay). The patients were divided into a conventional group and a PCC group according to whether they were treated with PCC. Propensity score matching method was used to match the patients at a 1:1 ratio, and the differences in different indicators between the groups were compared. Univariate and multivariate logistic regression analyses were performed to identify prognostic factors for TIC patients.Results:After propensity score matching, 103 patients were identified in both the PCC and conventional groups. Univariate logistic regression analysis revealed no significant differences in age, gender, Glasgow Coma Scale (GCS) score, injury severity score, acute physiology and chronic health evaluation score, underlying diseases, pre-hospitalization time, injury type and site, and treatment measure (use of vasoactive drugs, calcium agents, tranexamic acid, and emergency surgery) between the two groups (all P>0.05). Compared with the conventional group, the PCC group exhibited lower 24-hour white blood cell counts, lactate level, prothrombin time, and international normalized ratio (INR) (all P<0.05), whereas hemoglobin level and pH value were higher (both P<0.05). The PCC group also had a shorter hospital stay (13 d vs. 15 d, P<0.05). However, there was no significant difference in the rate of improvement at discharge between the two groups ( P=0.308). Multivariate logistic regression revealed that age (>68 years), GCS score (<5 points), fibrinogen (FIB) level (after 24 h, <2.04 g/L), and INR (after 24 h, >1.455) were independent risk factors affecting the prognosis of TIC patients, and the AUCs were 0.632, 0.702, 0.733, and 0.752, respectively. Conclusions:Treatment with PCC in TIC patients can correct coagulation dysfunction and reduce hospital stay. Age, GCS score, FIB level and INR after 24 h affect the clinical prognosis of TIC patients, which requires special attention.

Objective:To investigate the clinical characteristics and risk factors associated with secondary systemic capillary leak syndrome (SSCLS) induced by acute organophosphorus pesticide poisoning (AOPP). The goal is to enhance clinical understanding of this complication and provide a theoretical foundation for the early identification of high-risk patients and the optimization of individualized treatment strategies.Methods:Clinical data were collected from patients admitted to the Emergency Department of Fuyang People’s Hospital Affiliated to Anhui Medical University between October 2019 and October 2024, who were diagnosed with acute dichlorvos poisoning. The clinical features of SSCLS were described, and patients were categorized into SSCLS and non-SSCLS groups. Binary multivariate logistic regression analysis was conducted on statistically significant indicators to identify independent risk factors for SSCLS. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive value of these factors.Results:Among the 96 patients studied, 37 (38.5%) developed SSCLS. The median time from toxin ingestion to the onset of SSCLS was 3.0 (2.0-5.0) hours. In the 14 SSCLS survivors, the median duration of SSCLS was 50.0 (24-72) hours, whereas in the 23 non-survivors, it was 24.0 (12.0-35.0) hours. The mortality rate in the SSCLS group (62.16%, 23/37) was significantly higher than that in the non-SSCLS group (1.69%, 1/59) ( χ2=44.343, P<0.001). Blood toxin analysis detected trichlorfon components in 92 patients (95.83%). Binary multivariate logistic regression identified APACHE Ⅱ score and trichlorfon concentration (≥706.35 ng/mL) as independent risk factors for SSCLS ( P<0.05). ROC analysis revealed that the combination of these two factors had a higher predictive value ( P<0.05). Conclusions:In the diagnosis and treatment of acute dichlorvos (organophosphorus pesticide) poisoning, particular attention should be given to the combined toxic effects of dichlorvos and trichlorfon, which can lead to SSCLS. The onset and progression of SSCLS are rapid, and the condition is associated with a high mortality rate. Both APACHE Ⅱ scores and trichlorfon concentrations (≥706.35 ng/mL) are independent risk factors for the development of SSCLS, and their combined use enhances predictive accuracy. Early identification of high-risk patients and timely administration of individualized treatment are critical for reducing mortality rates. This revised abstract maintains the original meaning while improving clarity, flow, and readability. It ensures that the key points are presented in a structured and professional manner, suitable for a clinical audience.

Objective:To investigate the effects and mechanisms of subchronic exposure to pyrethrin on the mice nervous system.Methods:Twenty-four male mice were randomly divided into a control group,low-,medium-,and high-dose groups,and were exposed continuously for 28 days.The control group received corn oil.The general condi-tion of the mice was observed,and the body weight and brain organ coefficient were measured.Neurobehavioral tests were conducted after the exposure period.The histopathological changes of the hippocampus in mice were observed by HE and nissl staining.The activities of lactate dehydrogenase(LDH),superoxide dismutase(SOD),catalase(CAT)and the contents of malondialdehyde(MDA),glutathione(GSH),acetylcholine(ACh)and glutamate(Glu)in brain tissue of mice were detected by biochemical kit.The Western blot was employed to measure the expression levels of kelch-like ech-associated protein 1(Keap1),nuclearfactorerythroid2-relatedfactor2(Nrf2),and heme oxygenase 1(HO-1)in brain tissue of mice.Results:Compared with the control group,the body weight of the mice in the high-dose group decreased,the brain organ coefficient increased,and the neurological function test showed that the mice had reduced autonomic activity,delayed nerve reflex,and impaired sensory and motor function.Histopathology showed that the hippocampal neurons in the middle-and high-dose groups presented with pyknosis,vacuolization,and disordered arrangement of the CA3 area.Biochemical analysis indicated that in the brain tissue of mice,the activity of LDH and the content of MDA were increased in the medium-and high-dose groups,while the activity of CAT and the content of GSH were decreased.The content of Glu was increased and the content of ACh was decreased.The activity of SOD was reduced in the low-,medium-,and high-dose groups.Western blot analysis showed that the expression of HO-1 and Nrf2 protein in the brain tissue of mice in the middle-and high-dose groups was down-regulated,while the expression of Keap1 protein in the high-dose group was up-regulated.Conclusion:Pyrethrin may cause damage to the nervous system by affecting the Keap1/Nrf2/HO-1 signaling pathway and neurotransmitter levels.

Calcitonin-negative medullary thyroid carcinoma(CNMTC)is a rare subtype of medullary thyroid carcinoma,characterized by normal serum calcitonin levels,which often leads to misdiagnosis or missed diagnosis.The pathogenesis of CNMTC remains unclear and may involve impaired secretion mechanisms or assay-related false negatives.Diagnostic approaches include ultrasound-guided fine needle aspiration cytology,serum CEA and ProGRP measurements,and RET gene testing.Surgical resection remains the mainstay of treatment,while neoadjuvant therapy may be considered in selected cases.This review summarizes recent advances in the understanding,diagnosis,treatment,and prognosis of CNMTC,aiming to provide clinical guidance for better management of this challenging condition.

Objective:To investigate the clinical predictive value of Ki67 proliferation index combined with preoperative serum Ctn for postoperative biochemical cure of medullary thyroid carcinoma (MTC) .Methods:Clinical data were collected from Dec. 2008 to Dec. 2024 from 90 patients with surgically confirmed MTC at China-Japan Union Hospital of Jilin University. The optimal cut-off value for preoperative Ctn prediction of biochemical cure (171.18pg/mL) was determined by the ROC curve; the Ki67 proliferation index cut-off value was adopted from the international MTC grading system standard (5%). Patients were divided into three groups based on the above cutoff values: double-low group (Ki67 <5% and Ctn <171.18pg/mL, n=23), single-high group (Ki67 ≥5% and Ctn <171.18pg/mL or Ki67 <5% and Ctn ≥171.18pg/mL, n=49), and double-high group (Ki67 ≥5% and Ctn ≥171.18pg/mL, n=18). The Kaplan-Meier method (Log-Rank and Trend test) was used to compare the differences in biochemical cure rates between groups, and the Cox proportional risk model was used to analyze the risk factors affecting biochemical cure. Results:The correlation between preoperative Ctn and Ki67 proliferation index was not significant. The three groups differed significantly in gender, tumor distribution, tumor size, vascular invasion, N stage, TNM stage, and biochemical cure ( P<0.05), with the double-high group being significantly associated with larger tumors, later N stage and TNM stage, and lower biochemical cure ( P<0.001). Kaplan-Meier analysis showed that the biochemical cure rate in the double-high, single-high, and double-low groups showed a stepwise improvement.Cox univariate analysis showed that tumor size, N stage, TNM stage, preoperative Ctn, and Ki67 combined with Ctn were risk factors for failure to biochemically cure; multivariate analysis confirmed that the double-high group was an independent risk factor ( P<0.05). In the single-high group, the biochemical cure rate of patients in the low Ki67-high Ctn group was lower than that of the high Ki67-low Ctn group and more malignant. Ki67 had less effect on biochemical cure and disease-free survival at the low Ctn level, and Ki67 was an independent risk factor for failure to biochemically cure at the high Ctn level ( P=0.023) and was significantly associated with disease-free survival ( P=0.004) . Conclusions:Serum Ctn is more sensitive than Ki67 index in predicting biochemical cure after MTC, and the correlation between the two was weak. Ki67 proliferation index alone has limited prognostic value, but combines with preoperative Ctn significantly optimize the prognostic assessment of patients.The role of Ki67 index varied at different Ctn levels.