Non-small cell lung cancer (NSCLC), as the predominant histological subtype of lung cancer, accounts for approximately 85% of all lung cancer cases. In recent years, immune checkpoint inhibitors (ICIs), represented by programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors, have achieved breakthrough advancements in patients with driver gene-negative NSCLC. They have been established as a key component of first-line treatment regimens and have significantly improved clinical outcomes. However, limited clinical evidence has emerged showing the phenomenon of histological transformation from NSCLC to small cell lung cancer (SCLC) in patients experiencing disease progression after ICIs monotherapy or combination therapy. Systematic research data on the clinical characteristics, molecular biological basis, and subsequent treatment strategies for such transformation events are currently lacking. This article reports a case of SCLC transformation occurring in a patient with KRAS-mutated lung adenocarcinoma after 16 months of ICIs combination therapy and provides a systematic review of 22 similar published cases. The study demonstrates that small cell transformation is a critical mechanism of immunotherapy resistance, and transformed patients exhibit poor prognosis. The research emphasizes the importance of dynamic monitoring of neuron-specific enolase (NSE) and standardized repeat biopsies during treatment, providing a basis for clinical practice. This aids in enhancing the recognition and management capabilities for this rare histological transformation, ultimately improving patient outcomes.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/immunology* ; Carcinoma, Non-Small-Cell Lung/immunology* ; Small Cell Lung Carcinoma/genetics* ; Male ; Middle Aged ; Female

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Ileocecal duplication is a rare congenital gastrointestinal abnormality,with lesions predominantly localized near the ileocecal valve and manifesting as cystic structures.Clinically,it presents with diverse symptoms,including abdominal pain,vomiting,abdominal mass,etc.However,symptoms such as intussusception and appendicitis are easily confused with it.Furthermore,the imaging features of ileocecal duplication are nonspecific,which further increases the risk of misdiagnosis.Treatment options include laparoscopic surgery and laparotomy.Notably,laparoscopic surgery is highly feasible,especially for infants and young children,and achieves a prognosis comparable to that of laparotomy.In the case report presented in this study,a 1-year-old male patient was admitted to the hospital due to abdominal pain.Definitive diagnosis could not be established through comprehensive imaging examinations,and the diagnosis of ileocecal duplication cyst was ultimately confirmed surgically.Additionally,the diagnosis,imaging features,treatment,and prognosis of ileocecal duplication are systematically collated and summarized.

Ileocecal duplication is a rare congenital gastrointestinal abnormality,with lesions predominantly localized near the ileocecal valve and manifesting as cystic structures.Clinically,it presents with diverse symptoms,including abdominal pain,vomiting,abdominal mass,etc.However,symptoms such as intussusception and appendicitis are easily confused with it.Furthermore,the imaging features of ileocecal duplication are nonspecific,which further increases the risk of misdiagnosis.Treatment options include laparoscopic surgery and laparotomy.Notably,laparoscopic surgery is highly feasible,especially for infants and young children,and achieves a prognosis comparable to that of laparotomy.In the case report presented in this study,a 1-year-old male patient was admitted to the hospital due to abdominal pain.Definitive diagnosis could not be established through comprehensive imaging examinations,and the diagnosis of ileocecal duplication cyst was ultimately confirmed surgically.Additionally,the diagnosis,imaging features,treatment,and prognosis of ileocecal duplication are systematically collated and summarized.

Background and purpose:DDX is an adenosine triphosphate(ATP)-dependent RNA helicase closely related to mRNA regulation,tumor proliferation and invasion.This article aimed to explore the effect of DDX6,a member of the DDX family,on the stability of CKMT1A mRNA,as well as the effect of the DDX6 CKMT1A axis on the proliferation and migration ability of human nasopharyngeal carcinoma cell CNE2 and its molecular mechanism.Methods:We retrieved the data of expressions of DDX6 and CKMT1A in human head and neck squamous cell carcinoma from The Cancer Genome Atlas(TCGA)database and performed a correlation analysis.Western blot was performed to detect the expressions of CKMT1A and DDX6 in human nasopharyngeal carcinoma tissues and normal nasopharyngeal tissues preserved by Affiliated Hospital of Nantong University.This study was approved by the Ethics Committee of Affiliated Hospital of Nantong University(Number:2022-L114).We used transwell assay to detect cell migration ability,EdU assay to detect cell proliferation ability,and colony formation assay to detect clone formation ability.We transfect with lentivirus and plasmids to construct sh-DDX6,sh-CKMT1A,sh-CKMT1A+sh-DDX6 and oe-CKMT1A cell models derived from the human nasopharyngeal carcinoma cell line CNE2,preserved by Affiliated Hospital of Nantong University,to clarify the impact of DDX6 and CKMT1A expression levels on the malignant biological phenotypes of nasopharyngeal carcinoma cells.BALB/c nude mice subcutaneous xenograft tumor model was constructed to detect the effects of DDX6 and CKMT1A on nasopharyngeal carcinoma cells in mice.RNA stability assay was used to detect the effect of DDX6 knockout on CKMT1A mRNA and further clarify the molecular mechanism of DDX6.Results:DDX6 was highly expressed,CKMT1A level was low in human nasopharyngeal carcinoma tissue,and DDX6 was negatively correlated with CKMT1A expression.DDX6 inhibited protein translation of CKMT1A by disrupting its mRNA stability.Low expression of CKMT1A in CNE2 cells enhanced cell migration and proliferation ability,while high expression inhibited migration and proliferation ability.Knocking out DDX6 reversed the progression of malignant behavior caused by downregulation of CKMT1A.Low expression of CKMT1A promoted tumor cell growth in BALB/c nude mice subcutaneous xenograft tumor model,while low expression of DDX6 inhibited tumor cell growth.Knocking out DDX6 and CKMT1A simultaneously restored the inhibitory effect caused by knocking down DDX6 alone.Conclusion:DDX6 in nasopharyngeal carcinoma cells disrupts the stability of CKMT1A mRNA,negatively regulates CKMT1A protein translation,upregulates the proliferation and migration ability of nasopharyngeal carcinoma cells,and promotes malignant progression of nasopharyngeal carcinoma.

Objective To explore the characteristics of blood vitamins A, B2, B6, B12, D, E, K1, K2 and folic acid and their correlation with severity in patients with metabolic-related fatty liver disease (MAFLD). Methods　From September to December 2022, a total of 473 cases of residents were recruited through community MAFLD screening activities and their health information was obtained through questionnaire survey and physical examination. The severity of hepatic steatosis was determined with FibroScan, and vitamin concentrations were determined with liquid chromatography-tandem mass spectrometry. Two independent samples' t-tests were used to assess the differences between the two groups, and univariate chi-square tests and multivariate logistic regression analysis were used to explore the related factors of MAFLD. Results　Of the 473 inhabitants, 195 (41.23%, 195/473) met the diagnostic criteria for MAFLD, including mild 43 (22.05%, 43/195) cases of fatty liver, 88 (45.13%, 88/195) cases of moderate fatty liver, and 64 (32.82%, 64/195) cases of severe fatty liver. Using healthy residents collected during the same period as controls, the overall mean of vitamins A, E, K1, and K2 in the MAFLD group was higher than that of the healthy group, with a statistical difference (P<0.05). Furthermore, the concentrations of vitamins A, E, K1 and K2 increased with the severity of fatty liver [R=0.149, P=0.004; R=0.245, P<0.001; R=0.110, P=0.032; R=0.129，P=0.012]. There were statistically significant differences (P<0.05) in the blood levels of vitamin A and E between patients with moderate or severe fatty liver and the healthy population. The blood vitamins K1 and K2 in severe fatty liver patients were also different from those of healthy people (P<0.05). However, there was no significance between folic acid, vitamin D, B2, B6, B12, and MAFLD (P>0.05). Through univariate chi-square analysis and multivariate logistic regression analysis, it was found that male [Wald=5.789, P=0.034，OR=1.598(1.037-2.463)] and vitamin E≥8.13 μg/mL[Wald=14.632，P<0.001，OR=2.378(1.522-3.674)] were risk factors for moderate and severe MAFLD. Conclusions The concentrations of vitamin A, E, and K in the blood are increased in patients with MAFLD compared to the healthy population, and they are positively correlated with the severity of MAFLD. ale gender and high levels of vitamin E may be related to moderate to severe MAFLD.

Humans ; Neoplasms, Second Primary/epidemiology* ; Neoplasms/epidemiology* ; Risk Factors ; Prognosis

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

Objective:To investigate the efficacy and safety of bronchoscopic lavage in children with severe adenoviral pneumonia.Methods:Patients with severe adenovirus pneumonia who were admitted to ICU department of Hunan Children′s Hospital for bronchoscopy were collected from February to June 2019 and divided into lavage group( n=36) and non-lavage group( n=15) in line with whether lavage was performed.Their results, namely, bronchoscopic diagnosis, blood gas analysis before and 2 hours, 24 hours and 48 hours after bronchoscopy, improvement time of clinical symptoms(fever and pulmonary moist rales), the positive rate of pathogen detection and mortality rate, main vital signs such as heart rate, respiratory rate, mean arterial pressure and bronchoscopy-related complications were recorded before and 1 hour, 2 hours and 24 hours after bronchoscopy. Results:A total of 51 children were collected, all of whom suffered from endobronchitis.More secretions were observed in the airways of 36 patients in the lavage group, and only a little or no secretions were observed in 15 patients in the non-lavage group.P/F value and PCO 2 at 2 hours, 24 hours and 48 hours after treatment in the lavage group were improved comparing to those before treatment and were superior to those in the non-lavage group( P<0.05). P/F values at 24 hours and 48 hours after treatment in the non-lavage group increased and PCO 2 decreased at 48 hours after treatment( P<0.05). The thermal duration, time to resolution of moist rales in the lungs in the lavage group were shorter than those in the non-lavage group( P<0.05). The mortality rate in the lavage group was lower than that in the non-lavage group[2.8%(1/36) vs.26.7%(4/15), P<0.05]. The positive rate of pathogen detection in lavage group was higher than that in non-lavage group[55.6%(20/36) vs. 20.0%(3/15), P<0.05]. There was no significant difference in heart rate, respiratory rate, and mean arterial pressure at each time point before and after bronchoscopic treatment( P>0.05). Associated complications were 11 cases of intraoperative transient hypoxemia, four cases of bronchial mucosal bleeding, and one case each of postoperative hypoxemia, intraoperative hypertension and hypotension.There was no significant difference in the incidence of complications between the two groups( P>0.05). Conclusion:Bronchoscopic lavage, in treating children with severe adenovirus pneumonia, may improve clinical symptoms, respiratory function, and rate of pathogen detection, reduce mortality, and is effective and safe.

OBJECTIVE: To study the clinical features of severe type 7 adenovirus pneumonia in children. METHODS: A retrospective analysis was performed for the clinical data of children who were diagnosed with severe type 7 adenovirus pneumonia from February to June, 2019. RESULTS: Among the 45 children, the male/female ratio was 3:2 and the median age was 14 months. All children had repeated fever, cough, and pulmonary moist rales, and the mean duration of fever was 14±4 days. The median time from fever to dyspnea was 8 days, and the time from fever to mechanical ventilation was 11.6±2.5 d. There was no significant increase in white blood cell count, with neutrophils as the main type. There were slight reductions in hemoglobin and albumin, while platelet and fibrinogen remained normal. There were increases in aspartate aminotransferase, lactate dehydrogenase, procalcitonin, and C-reaction protein. The detection rate of mixed pathogens was 84%. Effusion in both lungs was the major change on chest imaging (64%). Bronchoscopic manifestations were endobronchitis, tracheomalacia, and plastic bronchitis. The incidence rate of respiratory complications was 100%, and extrapulmonary complications mainly involved the circulatory system (47%), digestive system (36%), and nervous system (31%). Among the 45 children, 16 were administered with 400 mg/kg intravenous immunoglobulin (IVIG) daily for 5 days, with a mean duration of fever of 16±5 days, and 29 were administered with 1 g/kg IVIG daily for 2 days, with a mean duration of fever of 13±4 days; there was a significant difference in the mean duration of fever between the two groups (P=0.046). The overall mortality rate was 11%. CONCLUSIONS Severe type 7 adenovirus pneumonia in children has severe conditions, with a high incidence rate of complications and a high mortality rate, so it should be diagnosed and treated as early as possible.
Adenoviridae ; Bronchitis ; Female ; Fever ; Humans ; Infant ; Male ; Pneumonia, Viral ; Retrospective Studies