Acute myocardial infarction (AMI) and acute ischemic stroke (AIS) are leading causes of death and disability in the world population. Cardio-cerebral infarction (CCI) is a rare clinical syndrome of AMI combined with AIS, which refers to the critical symptoms of simultaneous acute focal neurological deficits and precordial pain or electrocardiogram changes. The incidence of CCI ranges from 0.09% to 1.6%, but patients have a critical condition, poor prognosis, and high mortality and disability rates. Due to the complexity of the condition, diverse etiology, and limited evidence and mechanistic research, the management of patients with CCI is challenging. This article summarizes the pathogenesis related to CCI, the effectiveness of drug treatment, indications for endovascular treatment, and the selection of surgical sequence, with the aim of shortening thrombolysis/endovascular treatment time and improving outcomes of patients.

The proteolysis targeting chimeras (PROTACs) technology has been rapidly developed since its birth in 2001, attracting rapidly growing attention of scientific institutes and pharmaceutical companies. At present, a variety of small molecule PROTACs have entered the clinical trial. However, as small molecule PROTACs flourish, non-small molecule PROTACs (NSM-PROTACs) such as peptide PROTACs, nucleic acid PROTACs and antibody PROTACs have also advanced considerably over recent years, exhibiting the unique characters beyond the small molecule PROTACs. Here, we briefly introduce the types of NSM-PROTACs, describe the advantages of NSM-PROTACs, and summarize the development of NSM-PROTACs so far in detail. We hope this article could not only provide useful insights into NSM-PROTACs, but also expand the research interest of NSM-PROTACs.

Objective:To investigate the molecular genetic and clinical characteristics of MEF2D-BCL9 fusion gene-positive acute B-cell lymphoblastic leukemia (B-ALL), and to provide the reference for the diagnosis and treatment of the disease.Methods:The medical record and experimental examination data of a 18-year-old female MEF2D-BCL9 fusion gene-positive B-ALL patient were retrospectively analyzed. The clinical manifestations and biological characteristics of MEF2D-BCL9 fusion gene-positive B-ALL were summarized.Results:This 18-year-old female patient was treated in a local hospital in December 2018 and was diagnosed as B-ALL. She achieved complete remission after chemotherapy and recurred at 6 months after the initial onset, and then she was admitted to Hebei Yanda Ludaopei Hospital in the 9 months after the initial onset.MEF2D-BCL9 fusion gene was detected through RNA-sequencing (RNA-seq) and verified by using polymerase chain reaction and Sanger sequencing. Bone marrow cell morphology was similar to mature B cells with vacuoles but without characteristic chromosome karyotype abnormalities. The patient achieved remission after VLD regimen chemotherapy, chimeric antigen receptor T-cell (CAR-T) therapy and bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT). She has maintained complete remission for 2 years at the last follow-up in February 2022.Conclusions:MEF2D-BCL9 fusion gene-positive B-ALL is characterized with high risk, early relapse and poor prognosis. These patients may benefit from CAR-T and allo-HSCT. It further emphasizes the importance of taking MEF2D-BCL9 fusion gene into the detection or identification by using RNA-seq, particularly for those newly diagnosed B-ALL patients in children and adolescents with specific bone marrow morphology.

Objective: To analyze the incidence and mutation characteristics of FLT3 gene mutation and clinical efficacy of tyrosine kinase inhibitor (TKI) in patients with mixed phenotype acute leukemia (MPAL). Methods: A total of 48 patients with MPAL who were admitted to Hebei Yanda Lu Daopei Hospital from June 2015 to February 2018 were retrospectively analyzed. The common mutated 58 genes in hematologic malignancies were detected by using amplicon-targeted next generation sequencing, of which internal tandem duplication (ITD) and point mutation occurred in the hotspot region of exon 14, 15 and 20 in FLT3 gene. Multiplex polymerase chain reaction (PCR) analysis was used to detect 35 gene fusions in hematological neoplams. Results: There were 7 cases of FLT3 mutation in 48 MPAL patients, which were all ITD mutations. The median length of the inserts of FLT3-ITD was 48 bp, and one MPAL patient carried 2 multiple length inserts simultaneously, and the median variant allele frequency (VAF) was 40.5% (7.9%-84.7%). There were no statistically significant differences in clinical and genetic characteristics between FLT3 mutation-positive and FLT3 mutation-negative MPAL patients (both P > 0.05). Among 7 FLT3 mutation-positive MPAL patients, 4 cases were often accompanied with RUNX1 mutation. A total of 4 MPAL patients with FLT3-ITD-positive received sorafenib or sunitinib combined chemotherapy, and 3 of them achieved complete remission. Conclusions ITD mutation is the main part in the FLT3 mutation of MPAL patients. FLT3-ITD-positive MPAL patients are often accompanied with RUNX1 mutation, which may benefit from targeted therapy with FLT3 kinase inhibitor.

Objective To investigate the clinical and molecular biological characteristics of mixed_phenotypic acute leukemia (MPAL) with SET_NUP214 fusion gene positive and extramedullary infiltration. Methods The clinical characteristics, diagnosis and treatment of one MPAL patient with SET_NUP214 and extramedullary infiltration who was admitted to Hebei Yanda Ludaopei Hospital in November 2017 were analyzed, and the literature was reviewed. Results The patient was diagnosed as MPAL with extramedullary infiltration. Gene detection found SET exon7_NUP214 exon17 fusion positive accompanied with PHF6, SRSF2 and NRAS mutations. After intensive chemotherapy, the patient achieved complete remission, and then received hematopoietic stem cell transplantation (HSCT), followed by early extramedullary relapse after transplantation, and achieved secondary remission after consolidation chemotherapy. Conclusions MPAL with SET_NUP214 fusion gene positive and extramedullary infiltration has a poor prognosis, and it is easy to relapse. Currently, HSCT is the best available treatment strategy for such patients.

Objective To understand the implementation and application situation of Hierarchical Diagnosis and Treatment Guidelines of Obstetrics in Sichuan Province (version 2016).Methods The sampling survey was performed on the obstetric medical staffs from the various medical institutions in whole province by the questionnaire survey and on-spot investigation,and some tertiary hospital experts were interviewed.Results A total of 2015 valid questionnaires (93.85 ％) were received.Among them,1 369 people (77.7 ％) read the Guidelines;1 752 (95.0 ％) people thought that the Guidelines had practical operability in their hospitals;the causes considering that it had no practical operability were mainly disagree with referral by pregnant women or their family members,cumbersome referral,beds tension in superior hospital,etc.Improper referral sequencing was improper diagnosis and treatment during the referral process,non-standardized referral process,improper referral timing,no referral indications and so on.Conclusion The Guidelines promote the progress of obstetric hierarchical diagnostic and treatment work.It is necessary to strengthen the training of grassroots medical personnel and strengthen the management,supervision and assessment of referral.

Objective To investigate the expression of a proliferation-inducing ligand (APRIL) in urothelial carcinoma tissue and its clinical significance. Methods We investigated the expression of APRIL mR-NA in urothelial carcinoma tissue of 33 patients in urothelial carcinoma in Cangzhou Central Hospital from July 2013 to March 2015, Among of them, 23 cases of adjacent pericancerous tissues were detected by qRT-PCR. Immunohistochemistry and western blot were used to detect the APRIL protein expression level in urothelial carci-noma tissue and adjacent pericancerous tissues. We analyzed the relationship between APRIL expression and clinical pathology in patients with urothelial carcinoma by statistical methods. Results The qRT-PCR revealed that the expression of APRIL in urothelial carcinoma tissue was significantly higher than that in the adjacent peri-cancerous tissues (P < 0.05). Immunohistochemistry and western blot showed that the expression of APRIL in urothelial carcinoma tissue was higher than that in the adjacent pericancerous tissues. Correlation analysis found that the high expression of APRIL in urothelial carcinoma tissue was not significantly related to gender , age , size of tumor, lymph node metastasizing or not, and clinical stages (P > 0.05). Conclusion The APRIL is a high abnormal expression in urothelial carcinoma tissues , and maybe related to the occurrence and development of urothelial carcinoma.

Objective:To detect the expression of Shank1 protein in renal cell carcinoma (RCC), to investigate its difference between the tumor and carcinoma adjacent tissue, and to analyze its correlation with RCC clinicopathological characteristics and prognosis. Methods:The renal carcinoma and carcinoma adjacent tissues of 120 patients were selected from Cangzhou Central Hospital and Ji'nan Central Hospital from May 2008 to December 2014. The expression level of Shank1 was determined by immunohistochemistry and Western blot. Statistical analysis was performed to determine the relationship between the expression of Shank1 and the clinicopathological features of RCC patients. Results:Results of immunohistochemistry showed that the expression level of Shank1 in renal cancer tissue was significantly higher than that in carcinoma adjacent tissue, and the difference was statistically significant (P<0.05). Western blot results showed that the expression level of Shank1 protein in renal cancer tissue was also significantly higher than in carcinoma adjacent tissue. Correlation analysis found that the high expression level of Shank1 in renal cancer tissue was not significantly related to gender, age, tumor size, and TNM stage, but was significantly associated with the histological differentiation of RCC (P<0.05). Conclusion:Shank1 is abnormal y expressed in RCC renal cancer tissues and is correlated with the histological differentiation of RCC.

BACKGROUNDDistinguishing inverted papilloma (IP) from malignant tumors in the nasal cavity is difficult in a substantial number of cases, thus hindering the administration of appropriate therapeutic strategies. This study aimed to evaluate whether magnetic resonance imaging (MRI), including dynamic contrast enhanced MRI (DCE-MRI), could improve differentiation between IP and malignant tumors, and to identify which MRI features were the best in discriminating IP from malignant tumors in the nasal cavity.

METHODSNon-enhanced, static, and dynamic contrast enhanced MRI was performed in 88 patients with an IP or a malignant tumor in the nasal cavity that had been confirmed by histological results. MRI features of IP and malignant tumors including side, margin, T1 signal intensity, T1 homogeneity, T2 signal intensity, T2 homogeneity, lobulation signs, convoluted cerebriform pattern, extra-sinonasal involvement, pattern of enhancement, Tpeak, Tmax, CImax, and TIC type were evaluated and correlated with histological findings.

RESULTSThere were significant differences between IP and malignant tumors in T2 homogeneity, lobulation signs, convoluted cerebriform pattern, extra-sinonasal involvement, Tpeak, Tmax and TIC types. A convoluted cerebriform pattern had a higher sensitivity and specificity in diagnosis of IP while washout-type TIC had a higher sensitivity and specificity in diagnosis of malignant tumors in the nasal cavity. Non-enhanced combined with static and dynamic enhancement MRI was significantly superior to non-enhanced combined with static enhancement MRI in the differentiation of IP and malignant tumors in the nasal cavity. Multivariate logistic regression analysis identified that the best MRI features were a convoluted cerebriform pattern, extra-sinonasal involvement, and washout-type TIC for both observers (Wang XY and Zhang ZY).

CONCLUSIONNon-enhanced and static combined with dynamic contrast-enhanced MRI improves differentiation of IP and malignant tumors in the nasal cavity.

Adult ; Aged ; Contrast Media ; Female ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Nasal Cavity ; pathology ; Nose Neoplasms ; diagnosis ; Papilloma, Inverted ; diagnosis

Neural mass models are able to produce epileptic electroencephalogram (EEG) signals in different stages of seizures. The models play important roles in studying the mechanism analysis and control of epileptic seizures. In this study, the closed-loop feedback control was used to suppress the epileptic-form spikes in the neural mass models. It was expected to provide certain theory basis for the choice of stimulus position and parameter in the clinical treatment. With the influence of measurement noise taken into account, an unscented Kalman filter (UKF) was added to the feedback loop to estimate the system state and an UKF controller was constructed via the estimated state. The control action was imposed on the hyper-excitable population and all populations respectively in simulations. It was shown that both UKF control schemes suppressed the epileptic-form spikes in the model. However, the control energy needed in the latter scheme was less than that needed in the former one.
Computer Simulation ; Electroencephalography ; Epilepsy ; physiopathology ; Feedback ; Humans ; Models, Neurological