The transcription factor HOXB13 plays crucial roles in cancer development. HOXB13 is abnormally expressed in most cancers, which makes it a valuable therapeutic target for cancer therapy. The level of HOXB13 differs significantly between healthy and cancer tissues, which indicates that the level of HOXB13 is closely related to carcinogenesis. The regulatory network mediated by HOXB13 in cancer proliferation, metastasis, and invasion has been systematically investigated. Moreover, HOXB13 variants play distinct roles in different cancers and populations. By understanding the molecular mechanisms and mutation features of HOXB13, we provide a comprehensive overview of carcinogenesis networks dependent on HOXB13. Finally, we discuss advancements in anticancer therapy targeting HOXB13 and the roles of HOXB13 in drug resistance to molecular-targeted therapies, which serves as a foundation for developing HOXB13-targeted drugs for clinical diagnosis and cancer therapies.
Humans ; Neoplasms/metabolism* ; Homeodomain Proteins/metabolism* ; Carcinogenesis/genetics* ; Mutation ; Gene Expression Regulation, Neoplastic ; Molecular Targeted Therapy ; Drug Resistance, Neoplasm/genetics*

Objective·To investigate the expression of miR-146a in peripheral blood CD4+T lymphocytes of patients with rheumatoid arthritis(RA)and its correlation with inflammatory cytokines such as tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6).Methods·A total of 30 active RA patients who received medical treatment and 30 healthy controls who underwent physical examinations at the People's Hospital of Longhua,Shenzhen from August 2019 to July 2021 were selected.Peripheral blood mononuclear cells(PBMCs)and CD4+T lymphocytes were isolated from venous blood extracted from RA patients and healthy controls,respectively.Quantitative real-time PCR(qPCR)was used to detect the expression of miR-146a in peripheral blood CD4+T lymphocytes,and enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of TNF-α and IL-6.After transfection of the peripheral blood CD4+T lymphocytes of RA patients with miR-146a mimic,the expression of miR-146a,TNF-α and IL-6 was detected again.The correlations between miR-146a expression and TNF-α and IL-6 expression in RA patients,both before and after transfection,were analyzed by using Pearson correlation coefficient.Results·Before transfection with miR-146a mimic,the expression levels of miR-146a,TNF-α and IL-6 in peripheral blood CD4+T lymphocytes of RA patients were significantly higher than those of healthy controls(all P＜0.001).After transfection,the expression of miR-146a in peripheral blood CD4+T lymphocytes of RA patients was significantly higher,and the expression of TNF-α and IL-6 was significantly lower(all P＜0.001).The results of Pearson correlation analysis showed that the expression of miR-146a in peripheral blood CD4+T lymphocytes of RA patients,both before and after transfection,was positively correlated with the expression of TNF-α and IL-6,respectively(r=0.959,P＜0.001;r=0.916,P＜0.001;r=0.971,P＜0.001;r=0.861,P＜0.001).Conclusion·miR-146a can regulate the levels of TNF-α and IL-6 in peripheral blood CD4+T lymphocytes of RA patients,indicating that miR-146a may play a role in the pathogenesis of RA.

Objective To report single-center experience on CBA combined with LAAC in treat-ment of AF.Methods A retrospective study was conducted on 27 AF patients undergoing one-stop surgery of CBA combined with LAAC in Department of Cardiovascular Diseases of the People's Hospital of Liaoning Provincie from August 2020 to November 2022.The efficacy and safety of the surgery were analyzed.Results There were 22 patients(81.5％)with LAmbre and 5 patients with Watchman(18.5％,including one case of 24 mm Watchman FLX).All the patients achieved complete pulmonary vein isolation,and conversion to sinus rhythm during operation.During a mean follow-up of 30.0±9.2 months,24 patients(88.9％)maintained sinus rhythm at 12-month follow-up,and 22 patients(81.5％)maintained sinus rhythm at 24-month follow-up.TEE at 3 months after operation displayed that all the devices were in good positions and no PDL or DRT was observed.In the 11 patients undergoing cardiac enhanced CT in 12-36 months after surgery,PDL was detected in one patient(9.1％),and uncomplete endothelialisation of the device was observed in another one(9.1％)using the Watchman device.TEE at 26 months revealed one patient(3.7％)of DRT.Conclusion One-stop surgery of CBA combined with LAAC is a feasible treatment option for patients with NVAF and at high risk of stroke.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

  Objective  To evaluate the clinical and paraclinical features of Chinese patients with anti- LGI1 encephalitis.  Methods  Patients with memory deficits, psychiatric symptoms, seizures or altered level of consciousness, suspicious of encephalitis, at presentation to Peking Union Medical College Hospital were recruited between July 2013 and January 2018, and tested for anti-LGI1 antibodies in their serum and/or cerebrospinal fluid(CSF) samples. Patients with anti-LGI1 antibodies were enrolled. The demographic characteristics, clinical manifestations, laboratory examination results, neuroimaging features, immunotherapy, follow-up practices and outcomes for included patients were registered and analyzed.  Results  The study enrolled 120 patients, of whom 66.7% were male. The median age was 61 years (interquartile range [IQR]: 49-66 years). Seizures(65.0%) were the most common initial symptoms. Most patients developed seizures (95.0%), including faciobrachial dystonic seizures (54.2%), memory deficits (92.5%), and psychiatric symptoms (69.1%). Brain MRI and ¹⁸F-FDG PET / CT showed that the lesions were mainly located in unilateral or bilateral medial temporal lobes, and (or) basal ganglia. Of the patients, 95.0% received intravenous immunoglobulin (IVIg) or corticosteroids, 47.5% received mycophenolate mofetil as long-term immunotherapy, and no one received second-line immunotherapy. The median follow-up was 34.2 months(IQR: 22.0-45.6 months). 91.2% had a good outcome (modified Rankin Scale score≤2 points). Residual mild memory deficits were present in 47.8% of the patients. Nine deaths were documented. Relapses occurred in 24.8% of the patients in the first year. In total, 24 (20%)cases were young patients(onset age ≤45 years).There were fewer males among the younger patients(37.5% vs. 74.0%, P < 0.01). Besides, there were fewer younger patients with psychiatric symptoms(50.0% vs. 74.0%, P=0.02), hyponatremia(33.3% vs. 68.8%, P < 0.01), and abnormalities on brain ¹⁸F-FDG PET/CT(20.8% vs. 47.9%, P=0.02). The relapse-free survival rate was significantly higher in the young patients.  Conclusions  Elderly males were predominant in patients with anti-LGI1 encephalitis. Most patients developed symptoms of limbic encephalitis and/or FDBS during the disease course. Several patients were young adults and lacked typical symptoms. Neuroimaging features were consistent with the involvement of limbic system or basal ganglia. Patients with anti-LGI1 encephalitis respond well to immunotherapy, irrespective of the age.

BACKGROUND: Dabrafenib+Trametinib/Dabrafenib targeted therapy has been approved for V-RAF murine sarcoma viral oncogene homolog B1 with amino acid substitution for valine at position 600 (BRAF V600E) in lung cancer patients, however, the targeted therapy strategy for lung cancer patients with BRAF non-V600E mutations has not been determined yet. This study intends to explore the efficacy of targeted therapy for BRAF non-V600E mutant lung cancer, and provide a reference for clinical treatment. METHODS: Computer search of PubMed, Cochrane Library, Embase, Web of Science, Clinicaltrials.gov, CBM, CNKI, Wanfang database. Collect the relevant literature relevant on the targeted therapy of BRAF non-V600E mutant lung cancer, and conduct a descriptive analysis of the included literature. RESULTS: There were 10 articles that met the inclusion criteria, including 3 cohort studies and 7 case reports. 18 patients with BRAF non-V600E mutant lung cancer were ineffective to vermurafenib; 1 patient obtained partial response (PR) after applying vermurafenib, 5 patients did not respond to BRAF inhibitors; 9 patients showed a potential clinical benefit rate of 34% after monotherapy with trametinib; 7 patients have different degrees of benefit from dabrafenib and trametinib on progression-free survival (PFS); 1 patient is effective to sorafenib. CONCLUSIONS At present, there is no standard treatment specification for BRAF non-V600E mutation targeted therapy. The challenge lies in the heterogeneous mutation of BRAF gene. Different mutation types respond differently to targeted therapy. In addtion, real-world research evidence is scarce, so it is necessary to carry out further large-sample high-quality research to provide reference for clinical practice.
Animals ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; Lung Neoplasms/genetics* ; Mice ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins B-raf/genetics*

Objective:To investigate the value of dynamic contrast-enhanced(DCE)-MRI based textural analysis in differentiating IDH mutated high-grade gliomas from IDH gene wild types.Methods:Twenty-nine patients with high grade gliomas collected from April 2016 to December 2019 in First People's Hospital of Changzhou were assessed retrospectively, including 10 patients with IDH mutation and 19 patients with IDH gene wild type. All patients underwent DCE, conventional plain and enhanced MR scanning. Omni Kinetics software was used to perform DCE-MRI data processing, volume transfer constant (K trans), ratio constant of tracer refluxing from tissue to plasma (Kep), extravascular extracellular space per unit volume of tissue (Ve), blood plasma volume (Vp) and area under the gadolinium concentration-time curve (AUC) were obtained. Five commonly used textural features, including Energy, Entropy, Inertia, Correlation, and Inver Difference Moment (IDM), were generated based on gray-level co-occurrence matrices. The independent samples t test (normal distributionand equal variance) or Mann-Whitney rank sum test (abnormal distribution or unequal variance) was used to compare the differences in textural features of DCE-MRI parameters between IDH mutated group and IDH gene wild type group. Receiver operating characteristic (ROC) curves were used to evaluate the efficiency of textural features of DCE-MRI parameters in differentiating IDH mutated high-grade gliomas from IDH gene wild types for statistically significant textural features. Results:Entropy of K trans and Ve for IDH mutated group were 5.368±1.458 and 6.698±1.081, respectively; while the corresponding values were 7.334±1.385 and 8.213±1.320 for IDH gene wild type group, respectively. The difference between the two groups was statistically significant ( t values were-3.570, -3.113, P values were 0.001, 0.004, respectively). Inverse difference moment of K trans and Ve for IDH mutated group were 0.567±0.147 and 0.417±0.106, respectively; while for IDH gene wild type group, the values were 0.393±0.119 and 0.296±0.101, respectively. The difference between the two groups was statistically significant ( t values were 3.452, 3.014, P values were 0.002, 0.006, respectively). In all textural features, the area under the ROC curve of entropy of K trans was the largest (0.874), and the sensitivity was the highest (100%), and the specificity of IDM of Ve was the highest (94.7%). Conclusion:Textural analysis of DCE-MRI can help to differentiate IDH mutated high-grade gliomas from IDH gene wild types.

Objective: This study collected and analyzed data from patients with microtia in multiple clinical centers to obtain the incidence characteristics of microtia in Chinese. Methods: Data from 746 patients with microtia were collected from six hospitals, including theThird Hospital of Hebei Medical University, Hunan Provincial People′s Hospital, the Second Hospital of Hebei Medical University, Weihai Municipal Hospital, West China Hospital Sichuan University, Plastic Surgery Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2017. These data included the results of physical examination and the results of auxiliary examination such as electrocardiogram, chest CT, and abdominal ultrasound. Then, the accompanying malformations of the microtia were statistically analyzed and discussed. Data were entered and processed using SPSS 19.0 statistical software. The relationship between microtia deformities and associated malformations was analyzed by Pearson χ² test. P<0.05 was considered statistically significant. Results: A total of 746 patients with microtia were included, including 513 males and 233 females, aged 5-27 years old. There were 678 cases of unilateral microtia, 68 cases of bilateral microtia; 128 cases of Ⅰ degree, 564 cases of Ⅱ degree, and 54 cases of Ⅲ degree. In addition, 336 cases (45%) were associated with dysplasia of other systems. Detected anomalies were 321 cases of the ear, face, and neck, 261 cases of musculoskeletal system and 76 cases of cardiovascular system, 30 cases of anomalies of the urogenital system, eye, 27 cases of respiratory system, 7 cases of central nervous system, 5 case of digestive system and 1case of diaphragmatic hernia. The proportion of male and female with microtia was 47.0% (241/513) and 40.8% (95/233), respectively, and there was no significant difference in between (χ²=2.493, P=0.114); The composition ratios of unilateral and bilateral associated malformations were 45.7% (310/678) and 38.2% (26/68 ), and there was no significant difference in between (χ²=1.400, P=0.237); The composition ratios of Ⅰ, Ⅱ, Ⅲ degree-associated malformations were 39.8% (51/128), 42.6% (240/564), and 83.3% (45/54), and the difference was statistically significant (χ²= 34.794, P<0.001). Conclusions Microtia has significant clinical heterogeneity with a higher proportion of associated malformations. A higher incidence of associated deformities in patients with severe microtia was observed. Systematic examination is required, which will be helpful to clinical therapy and etiology analysis.

Objective To investigate the potential value of pre-treatment dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting long-term survival of cervical cancer treated by concurrent chemoradiotherapy. Methods Uterine cervical cancer patients who received chemo-radiation therapy during 2008 to 2014 in a single institute were retrospectively collected and followed up. Pre-treatment DCE-MRI images were retrieved to generate four hemodynamic related parameters including positive enhancement integral (PEI), maximum slop of increase (MSI), maximum slope of decrease (MSD) and signal enhancement ratio (SER). Region of interests were drawn manually on T2WI along the rim of tumors on each slice, and were then registered to DCE-MRI parametric maps. Histogram analysis software was used to calculate the mean, median, maximum, minimum,10th percentile, 90th percentile, kurtosis and skewness values for each DCE-MRI parameters. Median follow-up time was 54.7 months (range 2.1 to 94.6 months). Uni-and multivariable Cox regression analyses were used to evaluate correlation between the above values and the disease free survival (DFS). Kaplan-Meier curve was used to evaluate survival time. Results Of the 75 patients, 16 of them died from cervical cancer, 3 patients had metastasis, and 1 patient continued to progress. Median, mean, 10th and 90th percentile from MSI, and minimum, kurtosis, skewness were the influencing factors of disease-free survival of cervical cancer with concurrent chemoradiotherapy (P<0.1) Pearson relationship analysis and multivariable Cox regression analysis was performed which indicated PEI kurtosis value of cervical cancer was an independent influencing factor for cervical cancer without disease survival (hazard ratio 1.658, P=0.001). Conclusion PEI kurtosis was an independent factor for DFS of locally advanced cervical cancer treated with concurrent chemoradiotherapy.

Objective To investigate the effects of fasting serum triglycerides (TG) levels at different baseline on the risk of new-onset acute pancreatitis (AP) in in-service and retired employees of Kailuan Group.Methods A total of 125 178 in-service and retired employees of Kailuan Group who received health check-ups from 2006 to 2009 and had no AP history but had complete TG data were prospectively enrolled.According to quantile level,the baseline serum fasting TG level of study subjects were divided into ＜1.01 mmol/L group (n=42 128),1.01 to 1.64 mmol/L group (n=41 711) and ＞ 1.64 mmol/L group (n=41 339).The incidence of new-onset AP of these three groups was analyzed.The survival curve was plotted by Kaplan-Meier method.The cumulative incidence rate was calculated and tested by log-rank method.And multivariate Cox proportional hazards regression model was performed to calculate hazard ratios (HR) of baseline fasting serum TG level for AP.Results After followed up for (7.36±1.23) years,a total of 193 cases of AP occurred.The incidences of AP in ＜1.01 mmol/L group,1.01 to 1.64 mmol/L group and ＞ 1.64 mmol/L group were 1.43 events/10 000 person-years,2.37 events/10 000 person-years and 2.49 events/10 000 person-years,respectively.The cumulative incidence rates of AP in ＜1.01 mmol/L group,1.01 to 1.64 mmol/L group and ＞1.64 mmol/L group were 0.10％ (44/42 128),0.18％ (73/41 711) and 0.18％ (76/41 339),respectively,and the difference was statistically significant (x2 =9.998,P=0.007).The results of multivariate Cox proportional hazards regression model analysis indicated that the risk of AP increased in 1.01 to 1.64 mmol/L group and ＞ 1.64 mmol/L group compared with that of ＜1.01 mmol/L group,HR and 95％ confidence interval (CI) were 1.56 (1.07 to 2.29) and 1.57 (1.06 to 2.32),respectively.After excluded onset AP within one year,with a control group of ＜1.01 mmol/L group,the results of multivariate Cox proportional hazards regression model analysis indicated that the HR and 95％CI for AP of 1.01 to 1.64 mmol/L group and ＞ 1.64 mmol/L group were 1.70 (1.11 to 2.58) and 1.69 (1.10 to 2.60),respectively.Conclusion Baseline fasting serum TG levels over 1.01 mmol/L may increase the risk of AP.