Patients with anaplastic lymphoma kinase(ALK)fusion lung adenocarcinoma may develop drug resistance after treatment with ALK-tyrosine kinase inhibitor(ALK-TKI),and the mechanisms of this resistance are not yet fully defined.The Affiliated Hospital of Zunyi Medical University admitted a patient who was resistant to ALK fusion after ALK-TKI treatment,leading to disease progression and subsequent biopsy indicating a transformation to small cell lung cancer in September 2021.The patient,a 54-year-old female,initially presented with symptoms of cough,sputum production,and chest pain for 4 months.Chest CT showed a neoplastic lesion in the posterior segment of the right upper lobe to right lower lobe with obstructive pneumonia,metastasis in the right lower lobe,increased and enlarged mediastinal and right hilar lymph nodes,and thickening of the right hilar soft tissue.Bronchoscopy and pathological biopsy confirmed the diagnosis of lung adenocarcinoma.The results of next-generation sequencing indicated that echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase(EML4-ALK)fusion is associated with tumor protein 53(TP53)and retinoblastoma 1(RB1)gene mutations.The patient received second-generation ALK-TKI aletinib,achieving a progression-free survival of 11 months before disease progression suggested aletinib resistance.Subsequently,the third-generation ALK-TKI lorlatinib administered for one month without efficacy,resulting in rapid systemic disease progression.The neuron specific enolase(NSE)was significantly increased,and the patient developed new pleural,pericardial,intracranial,liver,and multiple bone metastases occurred in a short period.A second biopsy indicated small cell lung cancer.Modification of treatment regimen to chemotherapy combined with immunotherapy proved effective.The mechanisms of drug resistance of ALK-TKI treatment for advanced non-small cell lung cancer with ALK fusion are complex,and small cell transformation of pathological type is one such mechanism,although rare.Concurrent TP53 and RB1 gene mutations may be characteristic of this transformation.Elevated NSE can serve as a predictive serum marker for adenocarcinoma transforming to small cell carcinoma.Timely re-biopsy and selection of subsequent treatments based on different resistance mechanisms are crucial for comprehensive disease management.

Objective:To explore the value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) parameters in different regions of the kidney in distinguishing IgA nephropathy (IgAN) patients from healthy volunteers.Methods:This study was a cross-sectional study. Eighty-four patients diagnosed with IgAN (IgAN group) who underwent renal biopsy (lower pole of the left kidney) and were pathologically confirmed at the First Medical Center of PLA General Hospital from February 2022 to September 2023 and thirty-four healthy volunteers (control group) were included prospectively. The regions of interest were outlined in the right renal cortex, medulla, and parenchyma for all subjects, and the apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D *), and perfusion fraction (f) were measured in the corresponding regions. The differences in IVIM-DWI parameters between the IgAN group and the control group were compared using the student′s t-test or the Mann-Whitney U test. Receiver operating characteristic curve analysis was performed on the parameters with statistically significant differences, and the area under the curve (AUC) was calculated. Results:There were statistically significant differences in renal cortical ADC, renal parenchymal ADC, renal cortical D, renal parenchymal D, and renal medullary f values between the IgAN group and the control group ( Z=-3.03, -2.21, -2.62, -2.03, -2.03; P=0.002, 0.027, 0.009, 0.043, 0.042). The AUCs (95% CI) for diagnosing IgAN using renal cortical ADC, renal parenchymal ADC, renal cortical D, renal parenchymal D, and renal medullary f values were 0.679 (0.586-0.762), 0.630 (0.537-0.717), 0.654 (0.535-0.774), 0.619 (0.497-0.742), and 0.620 (0.495-0.745), respectively. There were no statistically significant differences in renal medullary ADC, D, renal cortex, medulla and parenchyma D *, renal cortical and renal parenchymal f values between the two groups ( P>0.05). Conclusion:The quantitative parameters of renal IVIM-DWI are influenced by different measurement regions, among which the ADC, D of renal cortex and parenchyma, and f of renal medulla can be used for the initial diagnosis of IgAN.

CRISPR-Associated Protein 9 ; Gene Editing ; CRISPR-Cas Systems/genetics*

The risk factors of acute kidney injury caused by strenuous exercise include dehydration of the body, elevated body temperature, and intake of large amounts of sugary drinks after exercise, etc. The possible mechanism of the injury may be the inflammatory reaction of the body or the kidney itself, and the accumulation of various metabolites causing damage to the structure and function of the kidney under the induction of various risk factors. Repeated exposure to those risk factors not only increase the risk of acute kidney disease, but also may lead to chronic kidney disease. The paper reviews the definition, epidemiology, clinical manifestations, pathogenesis, and prevention measures of exercise-related kidney injury, to provide guidance for the formulation of appropriate exercise programs.

In recent years, the prevalence of chronic diseases among children in China has increased significantly, which has become an important public health problem affecting children's health. This paper reviews the research status of family empowerment nursing for children with chronic diseases and elaborates from the aspects of intervention objects, nursing methods, nursing content and effects, as well as limitations and prospects, in order to provide a basis for exploring the norms and models of family nursing for children with chronic diseases in China.

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
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Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) system is a hotspot of gene editing and gene expression research, in which CRISPR/Cas13 system provides a new direction for RNA interference and editing. In this study, we designed and synthesized the corresponding gRNAs of CRISPR/Cas13a and CRISPR/Cas13b systems in non-homologous end joining (NHEJ) pathway, such as Ku70 and Lig4, and then detected the expression of ku70 and lig4 in HEK293T cells. The CRISPR/Cas13a system could efficiently knockdown the mRNA expression of ku70 and lig4 more than 50%, and CRISPR/Cas13b system also suppressed ku70 and lig4 about 92% and 76%, respectively. Also, CRISPR/Cas13a, b systems could down-regulate Ku70 and Lig4 proteins level to 68% and 53%, respectively. The study demonstrates that the CRISPR/Cas13 system could effectively knockdown the expression of RNA and protein in HEK293T cells, providing a new strategy for gene function and regulation research.
CRISPR-Cas Systems ; DNA Ligase ATP ; genetics ; Gene Expression Regulation ; genetics ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Ku Autoantigen ; genetics

Objective ToevaluatetheefficacyandsafetyofCT-guidedmicrowaveablation (MWA)forstageIVlungcanceraccompanied withcontrolledsingleintracranialmetastasis.Methods From November2011toOctober2016,78patientsinourhospitaldiagnosed withstageIVnon-smallcelllungcanceraccompaniedwithcontrolledsingleintracranialmetastasiswerestudied.Patientsweredividedintotwo groupsaccordingtowhethertheywerewillingtoacceptlocalMWAtreatmentornot:thegeneralgroup (groupA)with42cases, and MWAgroup(groupB)with36cases.Aftertheintracranialmetastasiswascontrolled,patientsingroupAweretreatedwithGP regimenforsimplechemotherapy,whilepatientsingroupB weretreatedwithlocalMWAcombinedwithGPregimen(gemcitabine combinedwithcisplatin).Allthepatientswerefollowed-upevery3monthsafterthesurgerytoassesstheefficacyandsafetyofthe correspondingtreatment.Thedeadlineofthefollow-upwasJune2017orwhenthetumorrestarteditsdevelopment.Results Thesuccessrateof theMWAofthe39lesionsinthe36patientsingroupBwas100%.TheKaplan-Meiersurvivalanalysisofthefollow-updataofthe twogroupsshowedthattheaverageprogressionfreesurvival(PFS)ofgroupA was(9.9 ± 0.8)monthsandthemedianPFSwas (8.0±0.5)months,whilethePFSofgroupB was (14.1±1.1)monthsandthe medianPFS was (15.0±1.5)months.The Log Rank testshowedthatχ2=8.780andP=0.03<0.05,whichreflectedthatthereweresignificantdifferencesinsurvivaltimebetweenthe twogroups.Theoverallsurvival(OS)ofgroupA was(20.5±1.1)months,andthemedianOSwas(21.0±1.3)months.TheOSof group B was (24.1±1.5)months,andthe median OS was (25.0±3.6)months.The Log Rank testshowedthat χ2=10.57and P=0.02<0.05, whichprovedthattheOSdifferencesbetweenthetwogroupshadstatisticalsignificance.ThemainadverseeffectsofMWA werepain,pleural effusion,pneumothorax,hemoptysis,infectionandsoon.There werenoseriouslife-threateningcomplicationsingroupB.Conclusion LocalMWAtreatmentforstageⅣnon-smallcelllungcancer withcontrolledsingleintracranialmetastasisisasafeandeffective method.Itisworthyofporularizing.

Objective To explore the techniques and strategies for the retrieval of the retractable inferior vena cava filter (IVCF).Methods Celect IVCF retrieval was not removed successfully with Gtünther Celect recovery device in 9 cases and exchange-wire-loop removal of inferior vena cava filter method were applicated.Results The longest implanted time of 9 patients was 142 days,the shortest implanted time was 37 days,and the average time was (88.67±33.85)days.Eight fil ters were successfully removed and one failed due to severe bending of inferior vena cava.Filter retrieval rate was 88.89％ (8/9).The average retrieval time was (69.89± 12.12)min (57-162 min).No perforation of the wall and contrast agent were found in all patients after the inferior vena cava angiography.Conclusion For the retrieval of the hook heavily atta ched to the IVCF,the retrieval technique of using the exchange wire into the loop method can effectively improve the retrieval rate and has a certain clinical value.

Objective To discuss the feasibility of the establishment of a Y-shaped channel with windowing technique in treating the stent shunt obstruction occurring after transjugular intrahepatic portosystemic shunt (TIPS).Methods From February 2012 to December 2016,puncture windowing technique was employed in 7 patients to establish a Y-shaped channel in order to treat the stent shunt obstruction complicated by gastric varices bleeding or ascites due to recurrent portal hypertension.The preoperative Child-Pugh scores of liver function ranged from 5 to 10 points,with a mean of (6.85±1.56) points.The blood flow in both the portal vein and the shunt was determined before operation as well as at 5 days and 1,3,6months after operation;the post operative results were compared with preoperative ones.Results Y-shaped channel was successfully reconstructed in all 7 patients.The patients were followed up for a mean of 11months.Neither death nor hepatic encephalopathy occurred.Conclusion For the treatment of post-TIPS stent shunt obstruction,Y-shaped channel reconstruction within the occluded stent by using windowing technique is safe and effective,the operation is simple and easy.Therefore,this technique has certain clinical value.