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.

Objective To determine the neurotoxic effects of amyloid beta 42(Aβ42)oligomers and investigate the mechanism of their induction of Alzheimer's disease(AD)-like pathogenesis in neuronal cells.Methods Western blotting and transmission electron microscopy were used to identify the synthesized Aβ42 oligomers.In order to assess the impact of the oligomers,MTT assay was employed to measure cell viability in neuroblastoma cell line SH-SY5Y treated with 10μmol/L Aβ42 oligomers for 12 or 24 h,glutamatergic neurons derived from human embryonic stem cells(hESC)exposed to Aβ42 oligomers for 24,48,or 96 h,and corresponding control cells.TUNEL assay was utilized to assess the apoptosis of glutamatergic neurons.Additionally,immu-nofluorescence assay was applied to detect the changes in Aβ plaques and p-tau pathology.Results Western blotting displayed monomers and small-molecule aggregation(＜30 000)in our synthe-sized Aβ42 oligomers,and transmission electron microscopy showed that the synthesized oligomers were mainly in a shape of spherical particles.Treatment of 10 μmol/L Aβ42 oligomers for 12 and 24 h in SH-SY5Y cells significantly decreased cell viability when compared with the control cells[(70.89±2.54)％vs(100.00±2.02)％,(52.63±3.37)％vs(100.00±2.80)％,P＜0.05].The 10μmol/L oligomers treatment for 24,48 and 96 h also decreased cell viability in glutamatergic neu-rons(P＜0.05).The apoptotic rates was significantly higher in glutamatergic neurons after treat-ment for 48 and 96 h when compared to the control cells[(1.44±0.31)％vs(1.00±0.38)％,(1.75±0.64)％vs(1.00±0.31)％,P＜0.05].Furthermore,circular granular Aβ-positive plaque signals were observed in the glutamatergic neurons after treated with the oligomers for 24,48,and 96 h,but no such plaque signals were seen in the control cells.Additionally,glutamatergic neurons incu-bation with 10 μmol/L oligomers for 24 h resulted in tau hyperphosphorylation at the Thr231 site,with the average fluorescence intensity significantly higher than that in control cells(P＜0.05).Conclusion Aβ42 oligomers show toxic effects to both SH-SY5Y cells and glutamatergic neurons,and they can also induce glutamatergic neurons to produce AD pathology.

Objective To analyze and discuss the medication rule of professor Ruan Yan in the treatment of children with allergic rhinitis by using data mining method,and to provide reference for the clinical research and patented drugs development for the treatment of children with allergic rhinitis.Methods The outpatient medical records of professor Ruan Yan for the treatment of children with allergic rhinitis were collected.Microsoft Excel 2010 software was used for frequency statistics.SPSS Clementine 12.0 software was used for association rule analysis,cluster analysis and factor analysis to obtain the data.The frequency of use of various drugs and the association rules between drugs were obtained.Then the medication rules in professor Ruan Yan's prescription were analyzed.Results A total of 308 Chinese medicine compounds were included,involving 80 kinds of Chinese medicines,among which relieving drugs and qi-invigorating herbs were high-frequently used.The distribution of traditional Chinese medicine syndrome types was mainly characterized by lung-qi deficiency-cold syndrome and lung-spleen qi deficiency syndrome.The medicinal properties were mainly spicy,warm and sweet,and most of them belonged to the lung,spleen and stomach meridians.Five core prescriptions were extracted by factor analysis.Four drug combinations were obtained by systematic cluster analysis.Conclusion Ventilating lung and opening the orifices,expelling wind and removing cold,strengthening the spleen and replenishing qi are basic therapeutic principles for professor Ruan Yan in the treatment of children with allergic rhinitis.The treatment mainly focused on dispelling evil,ventilating lung and opening the orifices,expelling wind and removing cold during the acute stage of allergic rhinitis.In the remission period,according to the principle of"treating disease must be based on its origin",the treatment should enhance children's physical fitness,tonify lung and strengthen spleen,thereby reducing recurrence.

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.

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.

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.