BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

Objective: To investigate the characteristics of breakthrough cases of varicella in Haishu District, Ningbo City, Zhejiang Province from 2017 to 2022, so as to provide the evidence for varicella prevention and control. Methods: Information on reported cases of varicella and vaccination in Haishu District from 2017 to 2022 were collected through the China Infectious Disease Reporting Management Information System and the Immunization Program Information Management System of Zhejiang Province. The breakthrough cases who had received 1 or 2 doses of varicella vaccine 42 days before the onset of disease were selected. The distribution of sex, age, region and the interval between onset and last immunization were descriptively analyzed. Results: A total of 1 563 varicella cases were reported from 2017 to 2022. There were 928 breakthrough cases (59.37%), of which 660 cases with 1-dose immunization history (42.23%) and 268 cases with 2-dose immunization history (17.15%). The proportion of 1-dose breakthrough cases in total annual cases showed a decreasing trend (P<0.05) from 2017 to 2022, while there was no significant tendency on the proportion of cases with 2-dose immunization history (P>0.05). There were 392 males (59.39%) and 268 females (40.61%) with 1-dose immunization history. There were 150 males (55.97%) and 118 females (44.03%) with 2-dose immunization history. Breakthrough cases with 1- and 2- dose immunization history had an median age of 13.00 (interquartile range, 4.00) and 9.00 (4.00) years, respectively, and the difference was statistically significant (P<0.05). The regional distribution of the breakthrough cases with 1- and 2- dose immunization history was mainly in the rural-urban fringe, with 319 cases (48.33%) and 137 cases (51.12%), respectively, and the difference was statistically significant (P<0.05). The median interval between onset and last immunization was 12.00 (interquartile range, 3.00) and 4.00 (3.00) years, respectively, and the difference was statistically significant (P<0.05). Conclusions The breakthrough cases of varicella in Haishu District from 2017 to 2022 were mainly cases with 1-dose immunization history, males, and residents in rural-urban fringe. The age was older and the interval between onset and the last immunization was longer in cases with 1-dose immunization history than in cases with 2-dose immunization history.

Objective To find out the social competence level of school-age children with speech sound disorders after cleft palate operation and functional speech sound disorders.Methods Thirty-four school-age children with postoperative cleft palate speech sound disorders and thirty-seven school-age children with functional speech sound disorders attending a specialty clinic for the diagnosis and treatment of childhood speech and language disorders in 2023 were selected,and 32 age-and gender-matched normal children in a local elementary school were also randomly selected as the normal group.The Achenbach Child Behavior Checklist was used to assess the so-cial competence of the three groups of children and a cross-sectional study was conducted.Results Children with cleft palate speech sound disorders and functional speech sound disorders had lower scores on activity,communication and academic ability,with specific manifestations varying in different gender groups,but there was no significant difference in scores between the two groups.In contrast,the activity and communication scores of the functional speech sound disordergroup were significantly lower than those of the normal group(P＜0.05).Conclusion School-age children with cleft palate speech sound disorders and functional speech sound disorders are at a higher risk of difficulties in social functioning,in terms of activity,communication and academic ability,whereas speech sound disorders may be one of the most important influencing factors of such difficulties and cleft palate does not have an additional impact on the social competence level of the child.

Background::Early detection of esophageal squamous cell carcinoma (ESCC) can considerably improve the prognosis of patients. Aberrant cell-free DNA (cfDNA) methylation signatures are a promising tool for detecting ESCC. However, available markers based on cell-free DNA methylation are still inadequate. This study aimed to identify ESCC-specific cfDNA methylation markers and evaluate the diagnostic performance in the early detection of ESCC.Methods::We performed whole-genome bisulfite sequencing (WGBS) for 24 ESCC tissues and their normal adjacent tissues. Based on the WGBS data, we identified 21,469,837 eligible CpG sites (CpGs). By integrating several methylation datasets, we identified several promising ESCC-specific cell-free DNA methylation markers. Finally, we developed a dual-marker panel based on methylated KCNA3 and OTOP2, and then, we evaluated its performance in our training and validation cohorts. Results::The ESCC diagnostic model constructed based on KCNA3 and OTOP2 had an AUC of 0.91 [95% CI: 0.85–0.95], and an optimal sensitivity and specificity of 84.91% and 94.32%, respectively, in the training cohort. In the independent validation cohort, the AUC was 0.88 [95% CI: 0.83–0.92], along with an optimal sensitivity of 81.5% and specificity of 92.9%. The model sensitivity for stage I–II ESCC was 78.4%, which was slightly lower than the sensitivity of the model (85.7%) for stage III–IV ESCC. Conclusion::The dual-target panel based on cfDNA showed excellent performance for detecting ESCC and might be an alternative strategy for screening ESCC.

Objective:To investigate any effect of combining mirror visual feedback (MVF) training with robot-assisted gait training (RGT) in promoting the recovery of lower limb motor function among stroke survivors.Methods:Sixty stroke survivors were randomly divided into a combined treatment group, an RGT group and a control group, each of 20. In addition to traditional rehabilitation, the RGT group received 30min of RGT 5 days a week for 4 weeks, while the combined treatment group underwent 30min of RGT and also 20min of MVF training with the same frequency and duration. Before and after the treatment, the lower extremities motor functioning and walking ability of all of the patients were assessed using the Fugl-Meyer Assessment for the lower extremities (FMA-LE), the Berg Balance Scale (BBS) and Functional Ambulation Categories (FAC).Results:There were no systematic differences in any of the measurements before the treatment. After the 4 weeks, however, the average FMA-LE, BBS and FAC scores of the combined treatment and RGT groups were significantly better than the control group′s averages, and those of the combined treatment group were significantly superior to the RGT group′s. All of the groups had, however, improved significantly compared with before the treatment.Conclusions:Robot-assisted gait training is more effective in enhancing the motor functioning of the lower extremities and walking ability when it is combined with MVF.

As guided by the policy of building national regional medical centers, it is imperative to advance the construction of the national regional medical centers for mental health to achieve the sustainable and balanced development of the mental health cause of the country. The authors summarized the current status of national regional medical centers, and analyzed challenges faced in management and operation mode, government investment and compensation mechanism, expansion of high-quality psychiatric medical resources, as well as research and innovation of mental diseases of these centers. On such basis, the authors put forward corresponding countermeasures and suggestions for the next stage of development.

ObjectiveTo study the effect of anodal transcranial direct current stimulation (atDCS) combined with mirror therapy (MT) on upper limb function for stroke patients. MethodsFrom July, 2018 to June, 2019, 54 stroke patients from the Department of Rehabilitation Medicine, Xuanwu Hospital, Capital Medical University, were randomly divided into groups A, B and C, with 18 cases in each group. All the patients received routine medication and rehabilitation training, while group A accepted 60 minutes of MT, group B accepted 20 minuts of atDCS first and then 40 minuts of MT, and group C accepted 40 minutes of MT first and then 20 minuts of atDCS in addittion; for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), Action Research Arm Test (ARAT), Motor Assessment Scale (MAS) and modified Barthel Index (MBI) before and after treatment. ResultsThe main effect of time was significant in scores of FMA-UE (F = 159.811, P < 0.001), ARAT (F = 353.227, P < 0.001), MAS (F = 513.494, P < 0.001) and MBI (F = 85.982, P < 0.001), and all of them improved after treatment. The main effect of groups was significant in scores of FMA-UE (F = 12.502, P < 0.001), ARAT (F = 20.095, P < 0.001), MAS (F = 16.371, P < 0.001) and MBI (F = 11.882, P < 0.001). The interacted-effect between time and groups was significant in scores of FMA-UE (F = 37.659, P < 0.001), ARAT (F = 78.681, P < 0.001), MAS (F = 97.997, P < 0.001) and MBI (F = 48.015, P < 0.001); while all the scores were the best in group B (P < 0.01), and there was no significant difference between groups A and C (P > 0.05). ConclusionThe combination of atDCS first and then MT can promote the recovery of motor function of the affected limbs for stroke patients.

Objective:To estimate the incidence and mortality of corpus uteri cancer in China, 2015.Methods:Quality audit and evaluation of the data from 2015 cancer registration reported by 501 cancer registries were conducted, and 368 cancer registries were included in the analysis. The incidence rate and mortality rate of corpus uteri cancer were calculated according to the factors of the region (urban, rural, east, central, western), sex and age groups. The incidence and mortality of corpus uteri cancer with the 2015 population were estimated. Chinese standard population in 2000 and world Segi′s population were used for the calculation of age-standardized rates (ASR) of incidence and mortality.Results:In 2015, 368 cancer registries included in the analysis covered a total of 309 553 499 populations in China, accounting for 22.52% of the national population. It is estimated that there were about 68 900 new cases of corpus uteri cancer in 2015, the incidence rate was 10.28/10 5, age-standardized incidence rates by Chinese standard population (ASR China) and world standard population (ASR world) were 6.86/10 5 and 6.66/10 5, respectively. The incidence rate of urban area (11.35/10 5) was higher than that of rural area (8.90/10 5), and the incidence of eastern region (12.12/10 5) was higher than the central region (9.94/10 5) and the western region (8.25/10 5). It is estimated that in 2015, there were about 16 000 deaths of corpus uteri cancer, the mortality rate was 2.39/10 5, ASR China was 1.49/10 5, ASR world was 1.47/10 5. The mortality in urban areas (2.40/10 5) is close to rural areas (2.39/10 5); the mortality in central areas (2.55/10 5) was higher than the eastern areas (2.32/10 5) and the western areas (2.31/10 5). Conclusions:In China, the incidence of corpus uteri cancer is on the rise and has a trend of youth, the burden of disease is gradually increasing, which threatens the health of women. Targeted prevention and control measures should be carried out in the different regions.

Objective:To estimate the incidence and mortality of corpus uteri cancer in China, 2015.Methods:Quality audit and evaluation of the data from 2015 cancer registration reported by 501 cancer registries were conducted, and 368 cancer registries were included in the analysis. The incidence rate and mortality rate of corpus uteri cancer were calculated according to the factors of the region (urban, rural, east, central, western), sex and age groups. The incidence and mortality of corpus uteri cancer with the 2015 population were estimated. Chinese standard population in 2000 and world Segi′s population were used for the calculation of age-standardized rates (ASR) of incidence and mortality.Results:In 2015, 368 cancer registries included in the analysis covered a total of 309 553 499 populations in China, accounting for 22.52% of the national population. It is estimated that there were about 68 900 new cases of corpus uteri cancer in 2015, the incidence rate was 10.28/10 5, age-standardized incidence rates by Chinese standard population (ASR China) and world standard population (ASR world) were 6.86/10 5 and 6.66/10 5, respectively. The incidence rate of urban area (11.35/10 5) was higher than that of rural area (8.90/10 5), and the incidence of eastern region (12.12/10 5) was higher than the central region (9.94/10 5) and the western region (8.25/10 5). It is estimated that in 2015, there were about 16 000 deaths of corpus uteri cancer, the mortality rate was 2.39/10 5, ASR China was 1.49/10 5, ASR world was 1.47/10 5. The mortality in urban areas (2.40/10 5) is close to rural areas (2.39/10 5); the mortality in central areas (2.55/10 5) was higher than the eastern areas (2.32/10 5) and the western areas (2.31/10 5). Conclusions:In China, the incidence of corpus uteri cancer is on the rise and has a trend of youth, the burden of disease is gradually increasing, which threatens the health of women. Targeted prevention and control measures should be carried out in the different regions.

Objective:To construct the teaching quality evaluation index system for clinical teachers of undergraduate nursing students based on teaching managers' perspective so as to provide a basis for clinical teaching management of undergraduate nursing students.Methods:From May 2018 to September 2019, the expert enquiry questionnaire on the teaching quality evaluation index system for clinical teachers of undergraduate nursing students based on teaching managers' perspective was developed by the literature review and expert interview. Delphi technique was used to select 20 nursing teaching management experts, 16 of them from 4 ClassⅢ Grade A teaching hospitals in Beijing, 4 of them from a nursing undergraduate university to carry out two rounds of expert enquiry.Results:The initial construction of the teaching quality evaluation index system for clinical teachers of undergraduate nursing students based on teaching managers' perspective included 5 first-level indexes and 30 second-level indexes. The valid recovery rates, expert authoritative coefficients, Kendall coordination coefficients of two rounds of expert enquiry questionnaire were 100%, 0.83 and 0.86, 0.395 and 0.554 respectively ( P<0.01) with the satisfied consistency test results and credible enquiry results. Conclusions:The construction of the teaching quality evaluation index system for clinical teachers of undergraduate nursing students based on teaching managers' perspective is scientifically rigorous. The system has definite evaluation indexes, rational administrative levels, objective and reliable system which could provide a basis for clinical teaching management of undergraduate nursing students.