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

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

The United States has established a perfect specialist training system for developmental and behavioral pediatrics (DBP), while the DBP specialist training system in China is still in the early stage of development and has been constantly improved. This article analyzes and compares the current status of DBP specialist training system between the United States and China from the aspects of training pattern, eligibility criteria, training plans and contents, assessment and evaluation, and certification. With reference to the training system in the United States, we can further improve the DBP specialist training system in China by perfecting the training system and related documents, constructing reasonable eligibility criteria, establishing a training pattern guided by post competency, improving the DBP assessment and evaluation system based on competency, and enhancing the certification of DBP physicians.

Objective: To investigate the epidemiological characteristics of respiratory syncytial virus (RSV) in hospitalized children in Ningbo City, so as to provide insights into developing prevention and control strategies for RSV. Methods: Basic information, clinical data and throat swab samples were collected from hospitalized children with respiratory infection in Ningbo University Affiliated Women and Children's Hospital from July 2019 to December 2023. Multiple fluorescence PCR-capillary electrophoresis was employed to detect nucleic acids of 11 non-bacterial respiratory pathogens. RSV detection in hospitalized children by time, gender and age was descriptively analyzed. Results: A total of 49 449 throat swab samples of hospitalized children with respiratory infections were detected. There were 4 310 samples positive for RSV, with a detection rate of 8.72%. The detection of positive specimens peaked from November to February in 2019 and 2020, from August to October in 2021, and from May to September in 2023. The RSV detection rate in boys was higher than that in girls (9.25% vs. 8.04%, P<0.05). The detection rate of RSV was highest in the children under 1 year of age (16.37%). The RSV detection rate tended to decrease with age (P<0.05). Among the specimens with positive RSV detection, 3 407 were positive for RSV alone (79.05%), while 903 were detected as mixed infections (20.95%). The non-bacterial pathogens with higher percentages of mixed detection were human rhinovirus, Mycoplasma pneumoniae and human parainfluenza virus. Conclusion Atypical seasonal epidemic of RSV infections appeared in 2021 and 2023 among hospitalized children in Ningbo City, with high detection rates in boys and children under 1 year of age, and a certain percentage of mixed infections.

To analyze the infection and drug-resistant gene 23S rRNA mutations of mycoplasma pneumoniae (Mp) in hospitalized children aged 0-17 in Ningbo City from 2019 to 2023. Throat swabs were collected from hospitalized children with respiratory tract infections in Ningbo University Affiliated Women and Children′s Hospital from 2019 to 2023. They were subjected to real-time fluorescence quantitative polymerase chain reaction detection to analyze Mp infection and drug-resistant gene (23S rRNA) mutations. Intergroup comparisons were made by the Chi-square test or Fisher′s exact probability method. A total of 18 968 hospitalized children were included, with a total positive rate of 30.37% (5 760/18 968). The total positive rate of drug-resistant gene mutations was 82.45% (4 749/5 760). The positive rate of Mp in male children was 29.26%, which was lower than that in female children (31.67%, χ 2=12.948, P<0.001). The positive rate of Mp drug-resistant gene mutations in male children was 82.52%, which was higher than that in female children(82.37%, χ 2=0.021, P=0.885). The positive rates of Mp increased with age ( χ 2=1 722.21, P<0.001). The positive rates of Mp drug-resistant gene mutations also increased with age ( χ 2=13.152, P<0.001). In the four seasons, the total positive rate of Mp in summer and autumn was significantly higher than that in winter and spring ( χ 2=1 085.149, P<0.001). Among them, the Mp positive rates in the summer and autumn of 2019 were as high as 38.26% and 34.49%, while in the summer and autumn of 2020, the Mp positive rates were 2.55% and 1.65%, respectively, which were the lowest in previous years. In the summer and autumn of 2023, the Mp positive rates increased to 47.22% and 51.06%. There was no statistically significant difference in the detection rate of Mp drug-resistant gene mutations among the four seasons. In Conclusion, Mp infection was more prevalent in the summer and autumn in Ningbo city and females and children aged 7-17 were more susceptible. The epidemic of Mp infection in Ningbo occurred in the summer of 2019. After the COVID-19 pandemic in 2020, the positive rate of Mp rapidly decreased and later remained in a low incidence state. After the lifting of restrictive prevention and control measures in 2023, the Mp positive rate returned to an epidemic state. The positive rate of Mp drug-resistant gene (23S rRNA) mutations was relatively high.

Objective This study aimed to investigate the effects of silencing Ras homolog family member C(RhoC)on the proliferation,apoptosis,invasion,migration,and epithelial-mesenchymal transition(EMT)of salivary adenoid cystic carcinoma(SACC)and its molecular mechanisms.Methods A total of 27 SACC lesions and normal salivary gland tissues that were surgically resected at Qingdao Municipal Hospital from January 1,2019 to March 1,2024 were selected,and the expression levels of RhoC were detected by Western blot and immunohistochemistry.Three small interfering RNA(siRNAs)were designed to target the RhoC gene sequence,transfected into SACC-LM and SACC-83 cell lines,and evaluated for transfection efficiency.The protein expression levels of RhoC,Rho-asso-ciated protein kinase-1(ROCK1),p38 mitogen-activated protein kinase(p38MAPK),phosphorylated-p38MAPK(p-p38MAPK),twist family bHLH transcription factor 1(TWIST1),E-cadherin,N-cadherin,and Vimentin were com-pared using Western blot.CCK-8 assay,flow cytometry,transwell invasion assay,and wound healing assay were conducted to assess the differences in cell proliferation,apoptosis,invasion,and migration abilities among the groups.Bioinformatics methods were also used to predict possible upstream micro RNAs(miRNAs)of RhoC and their expression levels in SACC.Moreover,dual-luciferase reporter gene experiments were performed to verify the binding sites of miR-138-5p and RhoC.Results RhoC was highly expressed in SACC(P＜0.05).After silencing RhoC,the test group showed a significant decrease in the expression level of ROCK1,p-p38MAPK,TWIST1,N-cadherin,and Vimentin,as well as a significant increase in the expression level of E-cadherin(P＜0.05).No signifi-cant difference in the expression level of p38MAPK was observed(P＞0.05).The cell proliferation,invasion,and mi-gration ability decreased in the test group,whereas the apoptosis rates significantly increased(P＜0.05).miR-138-5p was lowly expressed in SACC,and miR-138-5p mimic can significantly downregulated the luciferase activity of 293T cells after transfection with a RhoC wild-type plasmid(P＜0.05).Conclusion RhoC is highly expressed in SACC,and RhoC silencing may target the downstream ROCK1/p38MAPK/TWISTl signaling pathway,thereby in-hibiting the proliferation,invasion,migration,and EMT of SACC while promoting its apoptosis.On the contrary,miR-138-5p is lowly expressed in SACC and is a potential upstream gene of RhoC,and there may be binding sites between the two genes.

Objective To construct a nomogram risk prediction model for symptomatic cerebrovas-cular ischaemia based on intra-plaque neovascularisation in carotid arteries in patients with ische-mic cerebrovascular disease(ICVD).Methods A retrospective study was conducted on 320 ICVD patients who were consecutively admitted to Wuhan Fourth Hospital from April 2020 to April 2024.In a ratio of 3∶1,240 cases were assigned into a training set and 80 cases into a validation set.The patients in the training set were further divided into 147 cases in the symptomatic sub-group and 93 cases in the asymptomatic subgroup according to the presence or absence of relevant symptoms or signs.Multifactorial logistic regression analysis was used to identify the risk factors for symptomatic ischemia in ICVD patients,and a nomogram risk prediction model was construc-ted and the prediction efficacy of the model was evaluated.Results The proportions of plaque multiplicity,ulcerated plaque,stenosis ≥70％,and intra-plaque neovascularization were signifi-cantly higher in the symptomatic subgroup than the asymptomatic subgroup(P＜0.05,P＜0.01).Multifactorial logistic regression analysis showed that plaque multiplicity(OR=1.261,95％CI:1.088-1.539,P=0.003),ulcerated plaque(OR=1.458,95％CI:1.132-1.661,P=0.001),and stenosis ≥70％(OR=2.023,95％CI:1.458-2.561,P=0.001),and intra-plaque neovasculariza-tion(OR=1.206,95％CI:1.057-1.489,P=0.002)were independent risk factors for the occur-rence of symptomatic cerebral ischemia in ICVD patients.H-L deviation test showed that the con-structed nomogram risk prediction model had a good fit(x2=9.362,P=0.295).Internal and ex-ternal validation showed that the calibration curves for both the training and validation sets were consistent with the original curves,and the AUC value was were 0.871 and 0.864,respectively.De-cision curve analysis showed that the model had a significant standardized clinical net benefit when the predicted risk threshold exceeded 0.01.Conclusion Ultrasonography is instructive in as-sessment of the presence or absence of intra-plaque neovascularization in carotid atherosclerotic plaques.And our constructed nomogram risk prediction model has good predictive value for the development of symptomatic cerebral ischemia.

Missed diagnosis can often be noted in mild traumatic brain injury (mTBI), resulting from atypical symptoms, diverse performances and subjectively dependent report. Blood biomarkers can not only reflect the pathophysiological process of mTBI to a certain extent, but also have important clinical value in assessing brain injury severity and predicting adverse outcomes. This article systematically describes the research progress of blood biomarkers that can assist mTBI diagnosis, distinguish CT manifestations and predict prognoses in recent years, aiming to provide references for clinical application of blood biomarkers in mTBI.

Objective:To determine the expression of small nucleolar RNA host gene 16(SNHG16)in fibroblast-like synovio-cytes(FLS)of patients with rheumatoid arthritis(RA)and its role in the development of RA.Methods:RT-qPCR was performed to measure SNHG16,miR-182-5p and peroxisome proliferator-activated receptor gamma(PPARG)mRNA expression;dual-luciferase assay was performed to measure the interaction between SNHG16,miR-182-5p and PPARG mRNA;EdU and Transwell were per-formed to measure cell proliferation and invasion;Western blot was performed to measure PPARG protein level.Results:SNHG16 and PPARG mRNA expression were up-regulated and miR-182-5p expression was down-regulated in RA synovial tissue and human RA-FLS line(HFLS-RA).SNHG16 negatively targeted miR-182-5p expression and positively regulated PPARG(miR-182-5p target)expression.Silencing of SNHG16 inhibited the proliferation and invasion of HFLS-RA;down-regulation of miR-182-5p partially re-versed the inhibitory effect of SNHG16 silencing on cell proliferation and invasion;overexpression of PPARG partially reversed the in-hibitory effect of up-regulation of miR-182-5p on the proliferation and invasion of HFLS-RA.Conclusion:Silencing SNHG16 target-ing miR-182-5p/PPARG axis inhibits the proliferation and invasion of HFLS-RA.

To analyze the infection and drug-resistant gene 23S rRNA mutations of mycoplasma pneumoniae (Mp) in hospitalized children aged 0-17 in Ningbo City from 2019 to 2023. Throat swabs were collected from hospitalized children with respiratory tract infections in Ningbo University Affiliated Women and Children′s Hospital from 2019 to 2023. They were subjected to real-time fluorescence quantitative polymerase chain reaction detection to analyze Mp infection and drug-resistant gene (23S rRNA) mutations. Intergroup comparisons were made by the Chi-square test or Fisher′s exact probability method. A total of 18 968 hospitalized children were included, with a total positive rate of 30.37% (5 760/18 968). The total positive rate of drug-resistant gene mutations was 82.45% (4 749/5 760). The positive rate of Mp in male children was 29.26%, which was lower than that in female children (31.67%, χ 2=12.948, P<0.001). The positive rate of Mp drug-resistant gene mutations in male children was 82.52%, which was higher than that in female children(82.37%, χ 2=0.021, P=0.885). The positive rates of Mp increased with age ( χ 2=1 722.21, P<0.001). The positive rates of Mp drug-resistant gene mutations also increased with age ( χ 2=13.152, P<0.001). In the four seasons, the total positive rate of Mp in summer and autumn was significantly higher than that in winter and spring ( χ 2=1 085.149, P<0.001). Among them, the Mp positive rates in the summer and autumn of 2019 were as high as 38.26% and 34.49%, while in the summer and autumn of 2020, the Mp positive rates were 2.55% and 1.65%, respectively, which were the lowest in previous years. In the summer and autumn of 2023, the Mp positive rates increased to 47.22% and 51.06%. There was no statistically significant difference in the detection rate of Mp drug-resistant gene mutations among the four seasons. In Conclusion, Mp infection was more prevalent in the summer and autumn in Ningbo city and females and children aged 7-17 were more susceptible. The epidemic of Mp infection in Ningbo occurred in the summer of 2019. After the COVID-19 pandemic in 2020, the positive rate of Mp rapidly decreased and later remained in a low incidence state. After the lifting of restrictive prevention and control measures in 2023, the Mp positive rate returned to an epidemic state. The positive rate of Mp drug-resistant gene (23S rRNA) mutations was relatively high.