ObjectiveTo construct a stable monoclonal human embryonic kidney 293 （HEK293） cell line expressing recombinant human coagulation factor Ⅶ （rhFⅦ） and evaluate the expression level and procoagulant bioactivity of rhFⅦ. MethodsThe plasmid pCDNA3.1-EGFP-FⅦ was transfected into HEK293 cells to verify the effectiveness of the transfection system. The plasmid pCDNA3.1-FⅦ was transfected into HEK293 cells， and monoclonal stable transfected cell lines were selected using geneticin （G418）. The transcription of the FⅦ gene was identified by reverse transcription polymerase chain reaction （RT-PCR）. The expression level of rhFⅦ in the supernatant of the monoclonal stable transfected cell line was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot. The concentration of rhFⅦ was determined by enzyme-linked immunosorbent assay （ELISA）， and the procoagulant activity of rhFⅦ was measured by human coagulation factor Ⅶ potency assay. ResultsHEK293 cells transfected with pcDNA3.1-EGFP-FⅦ showed green fluorescence， indicating that rhFⅦ was successfully expressed in the supernatant of HEK293 cells after transient transfection with pcDNA3.1-FⅦ. The monoclonal stable transfected cell line was obtained by G418 screening. RT-PCR identified that the FⅦ gene was integrated into the genome of the monoclonal stable transfected cell line. The cell viability was good as detected by Cell Counting Kit-8， and a single band of rhFⅦ was obtained by purification of the cell supernatant. The highest rhFⅦ expression was （1.27±0.09） mg/L， and the highest procoagulant activity was （380.29±13.80）%. ConclusionThe monoclonal HEK293 cell lines which can express rhFⅦ protein efficiently and stably with excellent procoagulant bioactivity is successfully screened.

JMJD1C (Jumonji Domain Containing 1C), a member of the lysine demethylase 3 (KDM3) family, is universally required for the survival of several types of acute myeloid leukemia (AML) cells with different genetic mutations, representing a therapeutic opportunity with broad application. Yet how JMJD1C regulates the leukemic programs of various AML cells is largely unexplored. Here we show that JMJD1C interacts with the master hematopoietic transcription factor RUNX1, which thereby recruits JMJD1C to the genome to facilitate a RUNX1-driven transcriptional program that supports leukemic cell survival. The underlying mechanism hinges on the long N-terminal disordered region of JMJD1C, which harbors two inseparable abilities: condensate formation and direct interaction with RUNX1. This dual capability of JMJD1C may influence enhancer-promoter contacts crucial for the expression of key leukemic genes regulated by RUNX1. Our findings demonstrate a previously unappreciated role for the non-catalytic function of JMJD1C in transcriptional regulation, underlying a mechanism shared by different types of leukemias.
Core Binding Factor Alpha 2 Subunit/genetics* ; Humans ; Leukemia, Myeloid, Acute/pathology* ; Jumonji Domain-Containing Histone Demethylases/chemistry* ; Gene Expression Regulation, Leukemic ; Oxidoreductases, N-Demethylating/genetics* ; Cell Line, Tumor

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective:To compare the effectiveness between the unilateral biportal endoscopy (UBE) and the bilateral biportal endoscopy (BBE) decompression in the treatment of two-level central lumbar spinal stenosis (LSS).Methods:From January 2022 to April 2024, the clinical data of 31 patients with two-level central LSS treated with UBE and BBE unilateral approach with bilateral decompression were retrospectively analyzed. There were 17 males and 14 females; the age ranged from 60 to 82 years, with a mean of (71.2±5.9) years. The operative segments were L 2-3 and L 3-4 in 2 cases, L 3-4 and L 4-5 in 29 cases. Among them, 15 cases were treated with UBE and the other 16 cases were treated with BBE. The age, gender, course of disease, operation time, intraoperative fluoroscopy frequency, ambulation time, hospitalization days, incision healing grade and surgical complications were compared between the two groups. Visual analogue scale (VAS) and Oswestry disability index (ODI) were used to assess the low back and leg pain degree and functional improvement situation before operation, 3 months after operation and at last follow-up. Imaging examinations were performed before and after operation to evaluate the height of intervertebral space, the rate of articular process preservation and the area of dural sac in the two groups. Measurement data with normal distribution were represented as mean±standard deviation( ± s), and the comparison between groups was conducted using the t-test; measurement data with skewed distribution were represented as (interquartile range) [ M( Q1, Q3)], inter-group comparisons were conducted using the two-sample rank sum test, and intra-group comparisons before and after surgery were conducted using the rank sum test for two related samples or the rank sum test for multiple related sample data. The count data were represented as cuses and percentages, and the comparison between groups was conducted using the Chi-square test or Fisher exact probability method. Results:Thirty-one patients were successfully operated and followed up for 6-18 months, with an average follow-up time of (11.4±3.2) months. There was no significant difference in age, gender, course of disease, ambulation time and hospitalization days between the two groups ( P>0.05). There were significant differences between UBE and BBE in fluoroscopy frequency [(4.2±0.7) vs (2.3±0.4)] and operation time [(118.2±12.8) min vs (72.3±5.6) min] ( P<0.001). Three months after operation and at last follow-up, the VAS scores and ODI were significantly lower than that befor the operation, and the dural sac area was significantly larger than that before the operation in the two groups ( P<0.001), but there was no significant difference in VAS, ODI and dural sac area before or after operation between the two groups ( P>0.05). There was no statistical difference in the intervertebral height between the two groups compared to their respective preoperative measurements( P>0.05). The rate of articular process preservation on the operated side was about 80% in both groups. There were no complications such as dural nerve injury and hemorrhage in both groups. One patient in the UBE group had incision infection, which was improved after symptomatic treatment. Conclusions:Both UBE and BBE can achieve satisfactory effectiveness in the treatment of two-level central LSS, and the clinical effectiveness is similar. BBE can improve the operation efficiency, shorten the surgical duration and reduce the fluoroscopy frequency, so it has more advantages in the treatment of two-level central LSS.

Objective:To evaluate the safety and efficacy of tumor-treating fields (TTFields) and chemoradiation in patients with high-grade glioblastoma.Methods:Clinical data of 38 patients admitted to the Jiangsu Cancer Hospital from September 2021 to May 2023 who were diagnosed with high-grade glioblastoma (36 cases of World Health Organization grade Ⅳ and 2 cases of grade Ⅲ) were retrospectively analyzed. All patients received TTFields combined with concurrent chemoradiation after surgery. Response assessment in neuro-oncology (RANO) criteria was used to evaluate the glioma responses as tumor remission, stable or progression. Common terminology criteria for adverse events v5.0 and TTFields related skin adverse reaction (dAE) criteria were used to evaluate the adverse events. Treatment compliance was assessed by data on the NovoTTF-200A therapeutic device, calculated as a percentage of daily TTFields usage time. Survival analysis was estimated by the Kaplan-Meier method and compared by the log-rank test.Results:The median duration of treatment with TTFields in 38 patients was 20 h (rang: 2.4-22.6 h), and the median treatment compliance was 83% (range: 10%-94%). After 42 days of TTFields combined with concurrent chemoradiation, 12 patients who underwent complete tumor resection were assessed as stable according to RANO criteria. Among the 26 patients who underwent partial tumor resection, 23 (88%) were evaluated as disease remission according to RANO criteria. The 7-, 10-, 13-month progression-free survival rate was 81.0%、64.0%、49.5%, repectively. The common adverse events included grade 1 (45%) and grade 2 (8%) dAE, without grade 3-4 dAE. Typical presentations included contact dermatitis, blisters, lesions or ulcers, and abscesses. The median follow-up time was 10.0 months (range: 1.6-21.3 months). At follow-up as of July 2023, 26 of the 38 patients were stable and 12 had disease progression (8 died).Conclusion:The preliminary results show that TTFields combined with chemoradiation is effective, safe and reliable treatment for high-grade glioblastoma.

With the continuous development and maturity of anti-tumor immunotherapy technology,im-mune checkpoint inhibitors as one of the main methods of immunotherapy were increasingly widely used in clinical tumor cases,bringing new hope for many advanced cancer patients with poor response to tradi-tional treatment,but at the same time,reported on adverse reactions of various organs related to this were also increasing,and the immune damage caused by them was harmful to patients,especially immune checkpoint inhibitor-associated pneumonia,immune checkpoint inhibitor-associated myocarditis and im-mune checkpoint inhibitor-associated encephalitis,which could even seriously endangered the lives of pa-tients.Therefore,it was necessary for clinicians to fully understand and master the mechanism,clinical characteristics,laboratory and imaging examination characteristics,diagnostic criteria and differential di-agnosis conditions,and treatment principles of adverse reactions that may be caused by immune check-point inhibitors,so as to find a more optimized anti-tumor treatment regimen and actively prepared for the treatment of possible immune-related adverse reactions.In this paper,we reported a case of immune checkpoint inhibitor-associated severe pneumonia,referred to the relevant guidelines,introduced its clinical features,laboratory and imaging findings,difficulties encountered in the diagnosis and treatment process,briefly analyzed the causes,and reviewed the possibility of immune-related pneumonia should be considered when respiratory symptoms occurred in patients receiving immunotherapy;the increased ratio of blood neutrophil count to lymphocyte count,and the increased ratio of eosinophil count to lymphocyte count could be used as indicators to indicate immune-related adverse reactions in patients;bronchoalveo-lar lavage fluid examination and bronchoscopy and lung biopsy were helpful for the diagnosis;when im-mune checkpoint inhibitor-associated severe pneumonia occurred,in addition to symptomatic and sup-portive treatment,adequate glucocorticoid-based immunosuppressive therapy should be given in time,and combined with cytokines monoclonal antibodies and other biological agents,immunoglobulin co-therapy,but the current indications for the use of biological agents were not fully clear,and the use of high-dose immunosuppressive drugs might cause the risk of severe infection.Therefore,according to the relevant literature and the findings in the process of clinical diagnosis and treatment,this paper proposed that the serum levels of IL-6,TNF-α,CRP and other inflammatory mediators in patients may be used as a quantitative indication to initiate biological agent therapy and accumulate experience for better solving similar problems in the future.

With advancements in radiology,endoscopic techniques,surgical treatments,cell biology and molecular biology,the un-derstanding of temporomandibular disorders(TMD)has increased.The temporomandibular joint(TMJ)is a complex structure comprising both soft and hard tissues.Within the TMJ,the temporomandibular disc is a soft tissue structure that connects the mandible to the skull,providing cushioning and stability during joint movement.Different imaging techniques have their own advantages and limi-tations in the diagnosis and treatment of TMD.Therefore,using image registration technology to assess the condition and position of the articular disc provides new research perspectives for evaluating TMD,which may contribute to the diagnosis and treatment.This article reviews the latest advancements in TMJ imaging,explores the applications of various image registration techniques,particularly in the context of TMD diagnosis and treatment,and discusses future prospects.Combining the research results of some scholars at home and a-broad with the author’s clinical experience,the article aims to provide valuable insights for clinicians.

Objective:To assess the clinical features and effectiveness of antiviral therapy in newborns with sensorineural hearing loss (SNHL) caused by congenital congenital cytomegalovirus (cCMV) infection, and to speculate the risk factors for poor hearing outcomes.Methods:A multicenter prospective cohort study wasconducted, enrolling 176 newborns diagnosed with cCMV at four research centers in Zhejiang Province from March 1, 2021, to April 30, 2024. Clinical characteristics at birth were recorded and hearing was followed up. The children were divided into groups based on their condition at birth, specifically into asymptomatic, mild symptom, and moderate to severe symptom groups. Additionally, they were divided into SNHL and normal hearing groups based on the results of air conduction brainstem audiometry at birth. And they were also divided into treatment and untreated groups according to antiviral treatment. Mann Whitney U test, and chi square test were used for inter group comparison to analyze the differences in clinical features between different disease groups, and to analyze the effects of clinical features, antiviral therapy, and other factors on hearing improvement. Logistic regression analysis was employed to identify the risk factors influencing hearing outcomes. Results:Among the cohort of 176 children diagnosed infection with cCMV, 90 cases were male and 86 cases were female. Of these, 79 cases were asymptomatic, 12 cases classified as mild cCMV and 85 cases as moderate to severe cCMV. Fifty cases belonged to SNHL group, with different degrees of severity, including 30 cases of mild, 9 cases of moderate, 5 cases of severe, and 6 cases of extremely severe SNHL. Among the 121 cases in the normal hearing group, 2 cases (1.7%) exhibited late-onset hearing loss despite having normal hearing at birth. Among 81 cases (46.0%) who completed the hearing follow-up, 71 cases (87.7%) had good hearing outcomes and 10 cases (12.3%) had poor hearing outcomes. Among the 81 children, 29 cases (35.8%) had SNHL at birth. During follow-up, the hearing threshold improved in 19 cases (65.5%), remained stable in 7 cases (24.1%) and progressed in 3 cases (10.3%). A total of 26 cases in the treatment group and 55 cases in the untreated group completed the hearing follow-up assessment. The rate of hearing improvement in the treatment group was found to be higher compared to the untreated group (13 cases (50.0%) vs. 6 cases (10.9%), χ2=15.00, P<0.01), with individuals in the treatment group having a 4.58 times greater likelihood of experiencing hearing improvement ( RR=4.58,95% CI 1.96-10.70, P<0.05). However, no statistically significant difference was observed in hearing outcomes between the antiviral treatment group and the untreated group ( RR=0.90, 95% CI 0.57-1.41, P=0.517). Multivariate analysis further confirmed SNHL ( OR=11.58, 95% CI 2.10-63.93, P=0.005) and preterm birth ( OR=4.98, 95% CI 1.06-23.41, P=0.042) as independent risk factors for poor hearing outcomes. Conclusions:SNHL resulting from cCMV infection presents symptoms at birth and can be improved by antiviral therapy. Poor hearing outcomes are associated with SNHL and prematurity.

Objective To construct clinical imaging model,radiomics model,and a combined model based on the above two for predicting lymph node metastasis(LNM)of colon cancer(CC),and to compare the diagnostic performance of each model.Methods The data from 328 CC patients confirmed by surgical pathology were analyzed retrospectively,including 156 with LNM.All patients were randomly divided into training group(229 cases)and validation group(99 cases)at a ratio of 7∶3.The difference of clinical imaging indicators were compared between groups and a clinical imaging model for diagnosing LNM was constructed.The tumor three-dimensional volume of interest(VOI)was used for radiomics feature extraction,and after dimensionality reduction and selection,8 features were obtained to construct the Radiomics score(Radscore).A combined model of clinical imaging indicators and Radscore was built.The diagnostic performance of each model for LNM was compared,and the calibration and clinical benefit of the optimal model were evaluated.Results There were statistical differences in clinical imaging indicators between the two groups:carcinoembryonic antigen(CEA),CA199,tumor long diameter,and lymph node short diameter(P＜0.05).The area under the curve(AUC)of the clinical imaging model,radiomics model,and combined model were 0.721,0.814,0.854(training group),and 0.744,0.732,0.808(validation group),respectively.The AUC of the combined model was the highest,and both the training and validation groups were higher than that of the clinical imaging model(P＜0.05).The combined model demonstrated higher calibration,with a clinical benefit from decision curve analysis(DCA)threshold range of 0.09 to 0.91.Conclusion The nomogram constructed based on clinical imaging indicators and CT radiomics holds high value in diagnosing LNM of CC.

Objective To explore the clinical value of serum cysteine-rich protein 61(CYR61)and cardiac fatty acid-binding protein(H-FABP)in the diagnosis of neonatal acute respiratory distress syndrome.Methods A total of 105 children with acute respiratory distress syndrome who received treatment in the hos-pital from November 2020 to November 2022 were selected as the study group,and divided into mild group(42 cases),moderate group(35 cases)and severe group(28 cases).In addition,60 healthy newborns in the same period were selected as the control group.Serum CYR61 and H-FABP levels were detected and com-pared in all subjects after admission.Receiver operating characteristic(ROC)curve and area under curve(AUC)were used to evaluate the diagnostic value of serum CYR61 and H-FABP in neonatal acute respiratory distress syndrome.The related factors affecting the occurrence of neonatal acute respiratory distress syndrome were explored by multivariate Logistic regression.Results The levels of serum CYR61 and H-FABP in the study group were higher than those in the control group,and the differences were statistically significant(P＜0.05).Serum CYR61 and H-FABP levels in severe group were higher than those in moderate and mild groups(severe group＞moderate group＞mild group),and the differences were statistically significant(P＜0.05).ROC curve analysis showed that the AUC of serum CYR61 for neonatal acute respiratory distress syndrome was 0.843(95％CI:0.824-0.893).The AUC of serum H-FABP for neonatal acute respiratory distress syn-drome was 0.864(95％CI:0.814-0.914).The AUC of the combined detection for neonatal acute respiratory distress syndrome were 0.925(95％CI:0.875-0.975).Multivariate Logistic stepwise regression analysis showed that serum CYR61(OR=3.050,95％CI:1.738-5.352),H-FABP(OR=3.773,95％CI:1.845-7.717),C-reactive protein(OR=2.349,95％CI:1.584-3.483)and oxygenation index(OR=1.944,95％CI:1.444-2.619)were risk factors for neonatal acute respiratory distress syndrome(P＜0.05).Conclusion Ser-um CYR61 and H-FABP are both elevated in neonatal acute respiratory distress syndrome,and are closely re-lated to the severity of the disease,which are expected to be effective biological indexes for early diagnosis of neonatal acute respiratory distress syndrome.