BACKGROUND: Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. RESULTS: A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis. CONCLUSIONS: For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; ErbB Receptors/genetics* ; Lung Neoplasms/drug therapy* ; Mutation/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Chemoradiotherapy ; Antibodies, Monoclonal/therapeutic use*

Objective To investigate the effect of aqueous extract of Scrophularia ningpoensis(AESN)on AMP-activated protein kinase(AMPK)activity in INS-1 cells under high glucose(HG)conditions.Methods INS-1 cells were cultured in HG medium and treated with different concentrations of AESN.The influences of AESN on cell viability and pyroptotic body formation were detected using the CCK-8 assay.Western blotting was used to observe the effects of AESN on AMPK expression and phosphorylation.The effect of AESN on AMPK activity was measured using time-resolved fluorescence resonance energy transfer(TR-FRET)assay.Results Compared with normal glucose controls,INS-1 cells exposed to HG showed decreased cell viabilities and increased formation of pyroptotic bubbles using CCK-8 assay.Western blotting results indicated that HG exposure led to a decrease in intracellular AMPK phosphorylation levels.However,co-incubation with AESN under HG exposure AESN treatment increased the cell viabilities and phosphorylation of AMPK and decreased the pyroptotic bubbles formation in a concentration-dependent manner.In addition,the results of TR-FRET revealed that AESN treatment effectively increased AMPK activity in a concentration-dependent manner.Conclusion AESN has an activating effect on AMPK activity in HG-treated INS-1 cells.

This study summarizes the construction background, rules and regulations and institutional settings of the MOOC and Micro-course Club in the Second Hospital of Jilin University, discusses the means of teacher training for clinical teachers, and shows the application effect of the club. At the same time, the related problems encountered in the process of club construction are summarized and reflected. The construction of MOOC and micro-course clubs is conducive to improving the information-based teaching level of clinical teachers, and also provides new inspiration and ideas for the construction of medical clubs.

Iodine and fluoride are indispensable elements of human life activities,excessive or insufficient intakes can cause diseases,especially thyroid diseases,the relationship between iodine,fluoride and thyroid diseases has been paid more and more attention.The water iodine and fluoride are an important source of human intakes,so researching the influence of water iodine and fluoride on thyroid diseases is of great significance for guiding the population to maintain normal thyroid morphology and function.

Objective To explore the relationship between iodine and fluoride content in drinking water and the incidence of adult thyroid nodules in Cangzhou,Hebei.Methods According to the previous reports on iodine and fluoride levels in drinking water in Cangzhou,from November 2016 to January 2017,Cangzhou was divided into high iodine,low iodine,normal iodine and fluorine,low iodine and high fluorine,high iodine and high fluorine areas,and according to the different contents of iodine and fluorine in drinking water,high iodine and high fluorine area was further divided into high iodine and high fluorine 1 (iodine:743.30 μg/L,fluorine:4.27 mg/L),2 (iodine:119.31μg/L,fluorine:4.67 mg/L) and 3 (iodine:105.30 μg/L,fluorine:1.64 mg/L) subareas.Subjects who lived for 20 or more years and aged 30 or older,without serious disease and not taken iodized salt were selected.Palpation was used to examine the size,texture,mass,tenderness and mobility of the thyroid gland.The boundary,internal echo,blood flow and quantity of nodules were observed and recorded by color Doppler.Results The prevalence difference of thyroid nodules [36.8％ (629/1 710),32.8％ (636/1 938),25.1％ (427/1 700)] in high iodine,low iodine and normal iodine and fluorine areas was statistically significant (x2 =55.597,P ＜ 0.05).The prevalences of thyroid nodules in both high iodine and low iodine areas were higher than that of normal iodine and fluorine area (P＜ 0.016 7).The prevalence difference of thyroid nodules [43.3％ (749/1 730),39.8％ (712/1 790),34.9％ (623/1 785)] in high iodine and high fluorine 1,2 and 3 subareas was statistically significant(x2 =26.220,P ＜ 0.05).Compared with low iodine area,the prevalence of thyroid nodules [41.2％ (735/1 785)] in low iodine and high fluorine area was increased (x2 =6.288,P ＜ 0.05).Conclusions Both high iodine and low iodine can induce thyroid nodules.In water source areas with high iodine content,both high iodine and high fluorine are the factors inducing thyroid nodules.The prevalence of thyroid nodules in low iodine and high fluorine area is significantly higher than that of low iodine area.

Objective: To investigate the effects of Casein kinase 2-interacting protein 1 (CKIP-1) gene silencing on the proliferation of glioma cells U87-MG. Methods: The recombinant lentiviral vectors targeting CKIP-1 gene or negative control were constructed and then used to infect glioma U87-MG cell line.The effects of knock-down on the mRNA or protein expression of CKIP-1 were evaluated by real-time qPCR and western blotting.Cell cycle was detected by the flow cytometry assay, and cell proliferation changes were evaluated by cell counting, MTT, and BrdU assay, respectively.Lastly, the colony formation was used to investigate the effect of CKIP-1 knock-down on the clone formation. Results: Compared with the group of Ctrl, CKIP-1 siRNA was observed to significantly inhibit CKIP-1 expression at the mRNA levels (Ctrl (1.01±0.13) vs CKIP-1 siRNA (0.23±0.02), P<0.01) and protein levels in the U87-MG cells.Also, CKIP-1 suppression mediated by RNAi decreased the ratio of G0/G1 phase (Ctrl (69.64±0.79) vs CKIP-1 siRNA(62.64±0.66), P<0.01), increased that of G2/M phase (Ctrl (8.36±0.52) vs CKIP-1 siRNA(13.87±2.90), P<0.05), and significantly inhibited the cell proliferation and clone formation (Colony number: Ctrl (25±2) vs CKIP-1 siRNA(2±1), P<0.05) of transfected U87-MG cells. Conclusion Knocking down the expression of CKIP-1 significantly inhibit cell proliferation in human U87-MG glioma cells, indicating that CKIP-1 is involved in the development of gliomas and could promote the cell proliferation.

Objective:To discuss the accuracy of stereolithography (SLA)-3D printing model in orthopedics and maxillofacial surgery,and to clarify the reliability of its clinical application.Methods:A total of 33 cases of SLA-3D printing models were randomly included (10 long bones,13 irregular bones and 10 prostheses),and the CT scanning and three-dimensional reconstruction were performed.According to the clinical application characteristics of the models,the max height (MH),max length (ML),max width (MW),width of the trochlear (WT),length of the trochlear (LT),length of the glenoid cavity (LGC),width of the glenoid cavity (WGC),distance of pubic tubercle-anterior superior iliac spine (DPI),diameter of the acetabulum (DA),diameter of the marrow cavity (DMC),anterior height of right ramus (AHRR) and posterior height of right ramus (PHRR) were selected to measure the original data and model data,respectively.The absolute / relative errors were calculated.Intraclass correlation coefficient (ICC) was used to evaluate the consistency of the data.The three-dimensional error analysis of the prosthesis model was carried out.Results:There were no significant differences in the anatomical parameters except MW of irregular bone (P＞0.05) in 33 cases of SLA-3D printing model.The values of ICC were all greater than 0.950;the maximum values of absolute / relative errors were-0.58 mm and-1.37％,respectively;the maximum 3D error of prosthesis model was 0.237 mm,and the average value was 0.132 mm.Conclusion:The CT data of SLA-3D model is highly consistent with the original data,and it is accurate and reliable in the diagnosis and treatment of the diseases in orthopedics and maxillofacial surgery.

Objective To investigate the changes of cognitive impairment with disease progression in patients with minor stroke/transient ischemic attack (TIA).Methods Consecutive patients with minor stroke/TIA were enrolled prospectively.Montreal Cognitive Assessment (MoCA) was used to conduct the cognitive function assessment within 7 d of the onset (baseline),at 1 and 3 months,respectively.Compared with the baseline,the total scores of MoCA in patients increased by ≥2 at 3 months were cognitive function improvement and increased <2 were no cognitive function improvement.Multivariate logistic regression analysis was applied to identify the independent risk factors for no cognitive improvement.ResultsA total of 112 patients with minor stroke/TIA were enrolled in the study,including 63 patients (56.2%) with TIA and 49 (43.8%) with minor stroke.At baseline,1 month,and 3 months,77 (68.8%),72 (64.3%) and 60 (53.6%) patients had cognitive impairment.At 3 months after the onset,the cognitive function of 25 patients (22.3%) were improved,in which 19 (76.0%) and 6 (24.0%) patients had TIA/minor stroke respectively;87 (77.7%) did not have any improvement.Compared with the improvement group,the level of education was significantly lower (3.29±3.48 years vs.5.63±4.26 years;t=2.814,P=0.006),the level of glycosylated hemoglobin was significantly higher (6.35%±1.26% vs.7.21%±1.26%;t=-3.088,P=0.003) in the no improvement group,and the proportions of patients with minor stroke (49.4% vs.24.0%;χ2=5.101,P=0.024),hypertension (52.9% vs.24.0%;χ2=6.509,P=0.011),hyperlipidemia (51.7% vs.24.0%;χ2=6.019,P=0.014),diabetes (41.4% vs.16.0%;χ2=5.448,P=0.020),and coronary heart disease (32.2% vs.8.0%;χ2=5.792,P=0.016) were significantly higher.Multivariate logistic regression analysis showed that the level of education (odds ratio [OR] 1.364,95% confidence interval [CI] 1.059-1.756;P=0.016),atrial fibrillation (OR 2.509,95% CI 1.020-6.167;P=0.045),and higher glycosylated hemoglobin level (OR 1.586,95% CI 1.021-2.034;P=0.030) were the independent risk factors for no cognitive function improvement at 3 months after the onset of minor stroke/TIA.As time went on,the MoCA score and visual spatial execution,memory,abstract and directional scores were increased significantly (P<0.001),while there were no significant differences in naming,attention,and language scores.Conclusion s About 2/3 patients with minor stroke/TIA had cognitive impairment,and as time went on,they were improved.The lower education level,atrial fibrillation and higher baseline glycated hemoglobin were the independent risk factors for affecting no cognitive impairment improvement after monor stroke/TIA.

Objective: To investigate the metastatic sequence of cervical lymph node in hypopharyngeal carcinoma aimed at guiding neck exploration. Methods: Seventy-five serial sections of integrally dissected lateral neck specimens from 67 patients of hypophayryngeal carcinoma were histopathologically observed, and the metastatic sequence of cervical lymph node of hypophayryngeal carcinoma were analysed. Results: In 75 integrally dissected lateral neck specimens, 63 laterals were found to occur cervical lymph node metastases, the metastatic ratio was 84.0%. The analytic result of 63 dissected lateral neck specimens with positive lymph nodes showed that the metastatic lymph node ratio in descending order was level Ⅱ (90.5%), level Ⅲ (76.2%), level Ⅳ (41.3%), level Ⅴ (15.9%), level Ⅰ (7.9%) and level Ⅵ (3.2%). The metastatic ratio of lymph node between level Ⅰ~Ⅵ were significantly different from each other (P<0.01). When the tumor metastasized to one cervical lymph node, this could be found in levels Ⅱ or Ⅲ, when metastasized to two cervical lymph nodes, these could be found in levels Ⅱ, Ⅲ, Ⅳ, and when metastasized to more than 5 of cervical lymph nodes, these could be found in levels Ⅱ, Ⅲ, Ⅳ, Ⅴ, Ⅰand Ⅵ. According to the occurring sequence, metastatic ratio and number of cervical lymph node metastasis (LNM), levels Ⅱ and Ⅲ were identified as the first station, level Ⅳ was the second station and levels Ⅴ, Ⅰ and Ⅵ were the third station of cervical LNM in hypopharyngeal carcinoma. Conclusion The confirmation of metastatic sequence of cervical lymph node in hypophayryngeal carcinoma provides a reliable evidence for neck lymph node dissection and reference value for clinic therapy.

Objective To investigate the incidence,characteristics and risk factors of cognitive impairment in patients with transient ischemic attack(TI A) or minor stroke.Methods Montreal cognitive assessment(MoCA) was carried out in 279 patients with TIA or minor stroke and 150 healthy controls to assess their cognitive function.Results (1) Compared with the healthy controls,the TIA/minor stroke patients scored significantly lower on MoCA total score((23.98±2.55) vs (26.60±0.99),t=12.084,P＜0.01) and subtests including visuoexecutive function((3.68±0.94) vs (4.41±0.64),t=8.483,P＜0.01),digital span ((1.81±0.40) vs (1.95±0.23),t=3.771,P＜0.01),attention((0.84±0.37) vs (0.95±0.23),t=3.357,P＜ 0.01),repetition((1.59±0.62) vs (1.89±0.37),t=5.496,P＜0.01),verbal fluency((0.88±0.33) vs (0.95 ± ±0.23),t=2.286,P＜0.05),abstraction((1.55±0.64) vs (1.91±0.34),t=6.357,P＜0.01) and recall ((2.87±1.13) vs (3.18±0.41),t=3.281,P＜0.01) were significantly decreased.(2) Of 279 TIA/Minor stroke patients,213 (76.3％) suffered from cognitive impairment.The incidence of cognitive impairment was positively correlated with the gender,age,educational level,smoking,course,leukoaraiosis,comorbidities such as hypertension,diabetes mellitus(P＜0.05),and negatively correlated with hyperlipidemia(P＞0.05).Conclusion Extensive impairments of cognitive functions occur along with the incidence of TIA or minor stroke.It is thus suggested that cognitive assessment and interventions may be carried out at an early stage.