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 This study aims to investigate the role of genes related to fatty acid metabolism in periodon-titis through machine learning and bioinformatics methods.Methods Periodontitis datasets GSE10334 and GSE-16134 were downloaded from the GEO database,and the fatty acid metabolism-related gene sets were obtained from the GeneCards database.Differentially expressed fatty acid metabolism-related genes(DEFAMRGs)in periodontitis were screened using the"limma"R package.Functional enrichment and pathway analyses were conducted.Recursive Feature Elimination,Least Absolute Shrinkage and Selection Operator,and Boruta algorithm were used to determine hub DEFAMRGs and construct diagnostic models with internal and external validation.Subtypes of periodontitis relat-ed to hub DEFAMRGs were constructed using consis-tency clustering analysis.CIBERSORT was used to ana-lyze immune cell infiltration in gingival tissues and ex-plore the correlation between hub DEFAMRGs and im-mune cells.Results A total of 113 periodontitis DE-FAMRGs were screened out as a result.The enrichment analysis results indicate that DEFAMRGs are mainly associat-ed with immune inflammatory responses and immune cell chemotaxis.Finally,8 hub DEFAMRGs(BTG2,CXCL12,FABP4,CLDN10,PPBP,RGS1,LGALSL,and RIF1)were identified and a diagnostic model(AUC=0.967)was con-structed,based on which periodontitis was divided into two subtypes.In addition,there is a significant correlation be-tween hub DEFAMRGs and different immune cell populations,with mast cells and dendritic cells showing higher cor-relation.Conclusion This study provides new insights and ideas for the occurrence and development mechanism of periodontitis and proposes a diagnostic model based on hub DEFAMRGs to provide new directions for diagnosis and treatment.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

【Objective】 To explore the recruitment and retention strategy of blood donors by investigating the age composition of blood donors in some areas of China, so as to promote blood donation and enhance clinical blood supply. 【Methods】 Through the working platform of Practice Comparison Working Group of China’s Mainland Blood Collection and Supply Institutions, the average age and age composition of blood donors from 22 blood centers were collected, and statistical analysis was conducted after eliminating invalid data. 【Results】 The median average age of blood donors during the survey year was 30.02.The median age in 2.89% of the blood centers was lower than 25. The average age of different genders was statistically significant only in 2018(P<0.05). Fot first-time blood donors, the median constituent ratio of donors <25 and ≥25 years old was 54.53% and 44.28%, with median retention rate at 10.30% and 9.61%, respectively. The median overall participation rate of blood donors was 2.7%, with median participation rate of blood donors <25 years old at 5.1%. 【Conclusion】 The recruitment and retention of blood donor is crucial to enhance clinical blood supply. Blood donors <25 years old, with a longer period for future donation, should be the main target of blood donation recruitment. Meanwhile, the revision of upper age limit for blood donation is another important initiative to grow the blood donor pool.

【Objective】 To provide reference for fine management of blood donors by classifying and analyzing different types of blood donors from domestic blood stations. 【Methods】 The resident population of 15 regions in China from 2016 to 2019 were taken as the research object, among which the blood donors were divided into three categories: age-eligible citizens, registered donors and donated donors. The average value and proportion of the three categories were calculated and statistically analyzed. 【Results】 The resident population of the 15 regions varied greatly. The mean 95% CI of the proportion of age-eligible citizens to resident population from 2016 to 2019 was (60.16%, 67.84%); registered donors to age-eligible citizens and resident population was (2.21%, 2.86%) and (1.41%, 1.79%), respectively; donated donors to registered donors, age-eligible citizens and resident population was (84.63%, 91.68%), (1.93%, 2.55%) and(1.23%, 1.59%), respectively. 【Conclusion】 There were differences in the number and proportion of different types of blood donors in different regions. The fine management of blood donors can help blood stations carry out more effective recruitment and retention strategies.

Objective:To analyze of the transmission characteristics of a cluster of COVID-19 cases in Chongqing and evaluate the infectivity of COVID-19 in the incubation period.Methods:A retrospective survey was conducted by using unified questionnaire through field and telephone interviews among 129 close contacts of COVID-19 cases. The relationship of transmission was indicated by transmission chain, and the infectivity was analyzed by the contact history.Results:This cluster of COVID-19 cases occurred after a classmate party involving members in three families and work fellows in a factory ( R0=3.8). The infection rate during the incubation period was 17.57%. On average, it was infectious three days before onset. There was significant difference in infection rate among different contact modes ( χ2=15.10, P<0.01), There was significant difference in infection rate among single exposureswith different time length ( χ2=25.08, P<0.01). Conclusions:COVID-19 is highly infectious in the incubation period. The more confined the space is, the higher the risk is,and the longer the single exposure is, the higher the risk of transmission is. Indirect contact transmission still exists

Objective:To evaluate the efficacy and safety of cell sheets containing allogeneic keratinocytes and fibroblasts in the treatment of partial-thickness burn wounds.Methods:The cell sheets containing allogeneic keratinocytes and fibroblasts were constructed using polyurethane biofilm as carrier. Then gross observation and histological observation were conducted. From April 2016 to December 2017, Changhai Hospital of Naval Medical University recruited patients with acute partial-thickness burn wounds that met the inclusion criteria for this prospective and positively self-controlled clinical trial. Recruitment of 40 acute partial-thickness burn wounds were planned with each selected single wound being not smaller than 10 cm×10 cm and not more than 5% total body surface area (TBSA). Each wound was equally divided into two areas, which were recruited into cell sheet group and conventional treatment group according to the random number table. The wounds in cell sheet group were covered by cell sheet and then sterile gauze as secondary dressings. Depending on the wound healing and exudation, the sterile gauze was replaced every 1 to 3 day (s) after the treatment was started, and the cell sheet was replaced every 7 days (namely dressing changing). The wounds in conventional treatment group were covered by sulfadiazine silver cream gauze and then dressed with sterile gauze, with the dressings changed every 2 to 3 days depending on wound exudation. On treatment day 5, 7, 10, and 14, the wound healing rates in the two groups were calculated. The complete wound healing time, the total number of dressing changes, and the status of wound infection during treatment were recorded. The Visual Analogue Scale was used to score the pain at the first dressing change. Scar formation of patients was followed up for 6 to 12 months after injury. Safety indicators including vital signs, laboratory examination indexes, and adverse reactions during treatment were observed. Data were statistically analysed with Wilcoxon rank sum test and Bonferroni correction.Results:(1) Each prepared cell sheet had a diameter of about 8 cm and was about 49 cm 2 in size, containing 2 or 3 layers of keratinocytes and fibroblasts. (2) A total of 43 patients were enrolled, of whom 3 patients dropped out of the study. Of the 40 patients who completed the treatment, there were 22 males and 18 females who were aged 1 to 57 year (s), with total burn area of 2% to 26% TBSA. (3) On treatment day 5, 7, 10, and 14, the wound healing rates in cell sheet group were significantly higher than those in conventional treatment group ( Z=4.205, 4.258, 3.495, 2.521, P<0.05 or P<0.01). The complete wound healing time in cell sheet group was 7 (6, 8) days, which was significantly shorter than 11 (7, 14) days in conventional treatment group ( Z=4.219, P<0.01). The total number of wound dressing changes in cell sheet group was 1 (1, 2) times, which was significantly less than 6 (4, 7) times in conventional treatment group ( Z=5.464, P<0.01). (4) The wounds in cell sheet group in 31 patients healed before the first dressing change. The pain score of wounds in the first dressing change in cell sheet group of 9 patients was 1 (0, 1) point, while the pain score of wounds in the first dressing change in conventional treatment group of 40 patients was 2 (1, 3) points. There was no obvious infection in the wounds in both groups of 40 patients before the wound healing. Nine patients completed the follow-up after the trial. In 6 patients, no scar formation was observed in cell sheet group or conventional treatment group. The color of wounds in cell sheet group was consistent with normal skin, and there was only a small amount of pigment deposition in the wounds of conventional treatment group. Three patients developed pigment deposition only in the wounds of cell sheet group but obvious scars in conventional treatment group. (5) The abnormal fluctuations of vital signs including body temperature, blood pressure, heart rate, respiratory rate, and laboratory examination indexes of all patients during treatment were alleviated through the process of burn wound healing. No obvious adverse reactions or abnormalities related to the treatment were observed. Conclusions:The cell sheet containing allogeneic keratinocytes and fibroblasts can reduce the number of dressing changes, accelerate wound epithelialization, shorten wound healing time, reduce pain during dressing change in the treatment of partial-thickness burn wounds, and it may reduce scar hyperplasia after wound healing because of accelerating wound epithelization. Its clinical application is simple, safe, and effective.

Objective: To investigate the effect of endoscopic tympanic membrane repair in the clinical treatment of patients with chronic suppurative otitis media with tympanic membrane perforation. Methods: From November 2014 to September 2018, 72 patients with chronic suppurative otitis media with tympanic membrane perforation in Taizhou Central Hospital were divided into control group and observation group according to different treatment methods, with 36 cases in each group.The control group underwent microsurgical tympanic membrane repair, the observation group underwent endoscopic tympanic membrane repair.The bleeding volume and operation time of the two groups were compared.The pain degrees of the two groups were evaluated by numerical simulation scale (VAS). The postoperative hospital stay and complications were recorded.The postoperative follow-up of 6 months was used to evaluate the aesthetics of the two groups.The hearing improvement status and treatment effect of the two groups were evaluated. Results: The average surgical bleeding volume of the observation group was (6.14±1.25)mL, which was significantly less than that of the control group [(19.87±2.65)mL], and the operation time was (75.69±2.54)min, which was significantly shorter than that of the control group [(102.34±3.69)min](t=28.116, 35.694, all P<0.05). The VAS score of the observation group was (2.34±0.62)points, which was significantly lower than that of the control group [(3.59±0.85)points](t=7.128, P<0.05). The average length of hospital stay in the observation group was (4.89±1.25)d, which was significantly shorter than that in the control group [(9.18±1.36)d](t=13.935, P<0.05). The incision satisfaction of the observation group was significantly higher than that of the control group(P<0.05). The improvement in hearing of the observation group was (22.058±10.129)dB, which of the control group was (21.695±9.764)dB, the difference was not statistically significant (P=0.487). The effective rate of the observation group was 94.44%(34/36), which of the control group was 91.67%(33/36) (χ²=3.598, P=0.165). The incidence rate of complications in the observation group was 2.78%(1/36), which was significantly lower than 16.67%(6/36) in the control group(χ²=3.956, P=0.046). Conclusion Chronic suppurative otitis media tympanic membrane perforation patients treatment with endoscopic tympanic membrane repair is more effective, and the surgical method is better after surgery, so it is more acceptable to patients, it is worthy of promoting.

Objective To investigate the analgesic effects of inhaling 50% nitrous oxide on burn pediatric patients during and after dressing change. Methods A total of 120 burn pediatric patients received outpatient dressing and hospitalized from September 2012 to September 2014 were enrolled in our study, and they were all in accordance with the inclusion criteria. The 120 pediatric patients were divided into control group (n=30) treated with inhalation of oxygen during dressing change) and treatment group (n=90) treated with inhalation of 50% nitrous oxide during dressing change ) according to the computer-generated list of random number. The other treatments in control group and treatment group were the same. Before, during and after dressing change, degree of pain, heart rate, systolic blood pressure, diastolic blood pressure, oxygen saturation and adverse effects were observed at the same time points. Data were processed with analysis of chi-square test, covariance and Student′s t test. Results There were no significant differences between the two groups in levels of HR, SBP, DBP, and SpO2 before dressing change (t=0. 34, 0. 57, 0. 11, 0. 98, respectively;P>0. 05). Compared with those of control group, levels of HR, SBP, DBP, and SpO2 in treatment group were significantly ameliorated during dressing change (t=25. 96, 24. 11, 8. 37, 20. 29, respectively;P<0. 01). After dressing change, the levels of DBP in the two groups were close (t=1. 57,P>0. 05), but the levels of HR, SBP, and SpO2 showed statistical differences (t=5. 20, 8. 64, 3. 37, respectively;P<0. 01). Before dressing change, the pain scores were approximate between control group and treatment group (t=0. 18,P>0. 05). Compared with those in control group, the pain scores in treatment group during and after dressing change were (2. 82 ± 0.8) and (1.2 ±0. 84), which were significantly lower than those in the control group (t =23. 00, 4. 30, respectively;P<0. 01). There were no obvious adverse effects in two groups during and after dressing change. The results of the covariance analysis of pain scores during dressing change showed statistical differences ( F=867. 956,P <0. 01). Conclusions 50% nitrous oxide seems to have obvious analgesic effects on burns pediatric patients during dressing change, and it can be widely used.