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 analyze the clinical characteristics and prognosis of patients infected with novel coronavirus Omicron variant in Shanghai, as to provide a reference for epidemic prevention, clinical diagnosis, and treatment.Methods:Altogether 4 264 novel coronavirus Omicron variant-infected patients with positive results of nucleic acid admitted to Shanghai New International Expo Center N3 Mobile Cabin Hospital from April 2 to May 7, 2022, were included. The demographic and baseline clinical characteristics, treatment strategy, prognosis, and different factors affecting the length of hospital stay were analyzed.Results:A total of 4 264 novel coronavirus variant Omicron-infected cases were collected, including 3 111 cases (73.0%) asymptomatic infections and 1 153 cases (27.0%) mild infections. The overall median age was 45 (33, 55) years old with a range from 2 years old to 81 years old. The male to female ratio was 1.37∶1. Altogether 3 305 cases (77.5%) had been vaccinated, of which 3 166 cases completed more than 2 doses. The upper respiratory tract symptoms such as cough and expectoration were the most common clinical manifestations of these infected patients. During the course of the disease, patients with asymptomatic infection were mainly treated with traditional Chinese medicine (TCM, 55.1%) and clinical observation (36.8%), and those with mild infection were mainly treated with TCM (42.2%) or integrated Chinese and Western medicine (30.4%). All patients were cured and discharged. The overall median length of hospital stay and the negative conversion time of nucleic acid were 9 (6, 10) days and 8 (5, 9) days, respectively. Compared with the asymptomatic infected patients, the hospitalization duration and the nucleic acid negative conversion time of the mildly infected patients were slightly longer [days: 10 (8, 11) vs. 9 (5, 10); 8 (6, 10) vs. 7 (4, 9), both P < 0.001]. Multiple linear regression analysis showed that the increasing age and mild infection were associated with longer hospitalization duration, and the treatment of TCM or integrated Chinese and Western medicine was associated with shortened length of hospital stay (all P < 0.05). Conclusions:The current novel coronavirus Omicron variant epidemic in Shanghai mainly caused asymptomatic and mild infections. The young and middle-aged population had a relatively high infection rate. The upper respiratory tract symptoms such as cough and expectoration were the most common clinical symptoms. Elderly and confirmed patients had prolonged hospitalization duration, while for patients receiving TCM treatment, the hospitalization duration was shortened.

Objective:To explore the efficacy of the proximal tibial lateral locking plate with rafting screws combined with Jail screws in the treatment of collapse fracture of the lateral tibial plateau.Methods:A retrospective case series study was performed on clinical data of 36 patients with collapse fracture of the lateral tibial plateau admitted to Suqian Hospital of Nanjing Drum Tower Hospital Group from January 2016 to January 2020, including 19 males and 17 females, aged 34-68 years [(48.6±5.8)years]. Schatzker classification was type II in 28 patients and type III in 8 patients. All patients were treated using the proximal tibial lateral locking plate with raft screws combined with Jail screws. The operation time, intraoperative blood loss and fracture healing were detected. The distance of articular surface collapse of the tibial plateau, posterior inclination angle (PSA) of the tibial plateau, tibial plateau varus angle (TPVA) and Rasmussen anatomical score were compared before operation and at day 2 and 1 year after operation. The Hospital for Special Surgery (HSS) score was used to evaluate knee function at day 2 and 1 year after operation. Complications were also recorded.Results:All patients were followed up for 12-32 months [(19.5±3.1)months]. The operation time was 56-82 minutes [(68.5±9.1)minutes]. The intraoperative blood loss was 40-100 ml [(75.6±10.2)ml]. The fracture was clinically healed by first-stage, with the healing time of 8 to 15 weeks [(12.5±1.3)weeks]. The distance of articular surface collapse of the tibial plateau was improved from (15.5±4.2)mm before operation to (0.7±0.3)mm at day 2 after operation and (1.0±0.2)mm at 1 year after operation (all P<0.01). The PSA was improved from (21.2±2.1)° before operation to (8.9±0.8)° at day 2 after operation and (9.2±0.6)° at 1 year after operation (all P<0.01). The TPA was improved from (100.2±3.7)° before operation to (88.9±1.8)° at day 2 after operation and (87.2±1.6)° at 1 year after operation (all P<0.05). The Rasmussen anatomical score changed from (7.8±1.8)points before operation to (17.1±0.9)points at day 2 after operation and (16.3±0.7)points at 1 year after operation (all P<0.01). There were no significant difference in the distance of articular surface collapse of the tibial plateau, PSA, TPVA and Rasmussen anatomical score at day 2 and 1 year after operation (all P>0.05). The HSS score was (92.8±3.2)points at 1 year after operation, significantly higher than (74.8±3.5) points at day 2 after operation ( P<0.01). Two patients sustained superficial wound infection after operation, which healed after debridement and dressing change. No deep infection occurred. Conclusion:For patients with collapse fracture of the lateral tibial plateau, the proximal tibial lateral locking plate with rafting screws combined with Jail screws can effectively prevent secondary collapse of the articular surface and obtain satisfactory anatomical reduction, good functional recovery and few postoperative complications.

Objective:To compare the clinical effects of minimally invasive reduction through a bone tunnel combined with Jail screwing and those of posterolateral locking plating in the treatment of simple posterolateral tibial plateau fractures.Methods:A retrospective analysis was conducted of the data of 48 patients who had been operatively treated and completely followed up at Department of Orthopedics, Suqian Hospital of Nanjing Drum Tower Hospital Group for simple posterolateral tibial plateau fractures from October 2016 to October 2020. There were 26 males and 22 females, aged from 35 to 68 years. They were divided into a minimally invasive group (25 cases subjected to minimally invasive reduction through a bone tunnel combined with Jail screwing) and an incision group (23 cases subjected to posterolateral locking plating) according to their surgical methods. The operation time, incision length, intraoperative blood loss, fracture healing time, cumulative fluoroscopy time, hospital stay and posterior inclination angles of the tibial plateau and Hospital for Special Surgery (HSS) knee function scores at 1, 3, 6, 9, and 12 months after operation were compared between the 2 groups. Complications in the 2 groups of patients were recorded.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). The 48 patients were followed up for 12 to 36 months (average 16.5 months). The minimally invasive group was significantly better than the incision group in operation time [(42.6±9.1) min versus (65.7±11.5) min], incision length [(4.0±0.4) cm versus (15.0±1.5) cm], intraoperative blood loss[(22.6±5.8) mL versus (31.5±8.8) mL], hospital stay [(7.6±1.4) d versus (11.1±2.4) d], and HSS score one month after operation [(84.8±1.9) points versus (72.9±4.1) points], but the cumulative fluoroscopy time in the incision group [(4.1±1.4) s]was significantly less than that in the minimally invasive group [(22.3±4.2) s] ( P<0.05). There were no significant differences in fracture healing time, HSS scores at 3, 6, 9, or 12 months after operation, or posterior inclination angle of the tibial plateau between the 2 groups ( P>0.05). There were no such complications as wound infection, vascular injury, internal fixation failure, nonunion or malunion of fractures in either of the 2 groups. Two cases in the incision group presented with symptoms of common peroneal nerve injury but recovered 3 months after operation. Conclusions:Although both minimally invasive reduction through a bone tunnel combined with Jail screwing and posterolateral locking plating can achieve satisfactory outcomes in the treatment of simple posterolateral tibial plateau fractures, the minimally invasive technique is preferable because it shows the advantages of a smaller incision, less bleeding, shorter operation time, a lower operation risk, quicker postoperative recovery and shorter hospital stay.

Gonorrhea, caused by Neisseria gonorrhoeae, is one of the most frequently reported infectious diseases. With the increasing antibiotic resistance in Neisseria gonorrhoeae, gonorrhea has become a major public health problem worldwide, making it imperative to develop a safe and effective vaccine. Lipooligosaccharides (LOS), which exist on the outer surface of gram-negative bacteria, contain many important antigenic determinants. In recent years, a large number of studies have shown that LOS may become the most potential target of Neisseria gonorrhoeae vaccine and immunotherapy. This article reviewed the structure of LOS, its role in Neisseria gonorrhoeae infection, research progress in LOS vaccine and the challenges faced in vaccine development, aiming to provide reference for further study.

To rapidly and accurately manipulate genome such as gene deletion, insertion and site mutation, the whole genome of a very virulent strain Md5 of Marek's disease virus (MDV) was inserted into bacterial artificial chromosome (BAC) through homogeneous recombination. The recombinant DNA was electroporated into DH10B competent cells and identified by PCR and restriction fragment length polymorphism analysis. An infectious clone of Md5BAC was obtained following transfection into chicken embryo fibroblast (CEF) cells. Furthermore, a lorf10 deletion mutant was constructed by two step Red-mediated homologous recombination. To confirm the specific role of gene deletion, the lorf10 was reinserted into the original site of MDV genome to make a revertant strain. All the constructs were rescued by transfection into CEF cells, respectively. The successful packaging of recombinant viruses was confirmed by indirect immunofluorescence assay. The results of growth kinetics assay and plaques area measurement showed that the lorf10 is dispensable for MDV propagation in vitro. Overall, this study successfully constructed an infectious BAC clone of MDV and demonstrated its application in genome manipulation; the knowledge gained from our study could be further applied to other hepesviruses.
Animals ; Chick Embryo ; Chickens ; Chromosomes, Artificial, Bacterial ; DNA, Recombinant ; Herpesvirus 2, Gallid/genetics* ; Marek Disease

Background and objective Lung cancer in young patients (less or equal to 45 years) is relatively rare. We explored the effcacy and survival of Geiftinib for young patients with unknown epidermal growth factor receptor (EGFR) gene mutation of advanced lung adenocarcinoma. Methods hTe clinical data of 55 young patients with unknown EGFR gene mutation in advanced lung adenocarcinoma referred to the Cancer Hospital&Institute, Chinese Academy of Medical Sciences from Jan 2006 through Dec 2010 were analyzed retrospectively. Results Of 55 young patients enrolled, the me-dian age was 41 years. hTe objective response rate and disease control rate were 43.6%and 90.9%, respectively. hTe median progression-free survival (PFS) was 9.0 months. Among the factors analyzed, brain metastasis had signiifcant effect on PFS (P=0.017). hTe median overall survival (OS) was 24.0 months. hTe independent prognostic factors to signiifcantly improve OS included non-smoking history (P=0.028) and receiving other anti-cancer treatment atfer Geiftinib therapy (P<0.001). Conclusion hTe median PFS and OS of the young patients with Unknown EGFR gene mutation in advanced lung adeno-carcinoma were similar with general population.

Objective To investigate characteristics of memory-guided saccade in Parkinson' s disease (PD),and to evaluate the application of memory-guided saccade in diagnosing PD.Methods Fiftythree subjects with early- or mid- stage PD were chosen as PD group,meanwhile,36 age-matched healthy subjects were chosen as control group.Memory-guided saccade test and event-related potential P300 were performed in all subjects,and results of the two groups were compared; furthermore,results of subgroups comprised of 29 patients with early-stage PD were analyzed.Results In comparison with control group,memory-guided saccade in PD group showed decreased velocity and primary gain,prolonged latency,extremely increased incidence of unwanted saccade and multi-step saccade ( U =124.000,37.000;both P ＜0.01 ),such abnormalities has already stood out even in subgroup comprised of early-stage PD patients.Meanwhile,latency of event-related potential P300 in PD group was prolonged compared with control group ((384.76 ± 34.48) ms vs (352.42 ± 24.99) ms,t =- 4.791,P ＜ 0.01 ).Multi-step saccade measurement demonstrated excellent sensitivity (96.2％ ) and specificity (94.4％) in the ability to discriminate PD patients from controls.Conclusion Memory-guided saccade in PD patients shows highly abnormal which may reflect the impairment of pontine saccade pathway and the dysfunction of frontal lobe.Memory-guided saccade test may be a useful examination in assisting the diagnosis of PD.

Objective To investigate the association of serum ferritin and hemoglobin with the pathogenesis of primary restless legs syndrome(RLS). Methods Thirty-five patients with primary restless legs syndrome and twenty insomnia controls were included in this study. The level of serum ferritin and hemoglobin were measured, and the data have been analyzed using t-test. Results The level of serum ferritin in the primary RLS patients (89.77μg/L (SD:48.52)) was significantly lower than in the contruls (123.36 μg/L (SD:35.06)) (t=-2.713,P <0.01), whereas the level of hemoglobin have no statistical difference between the RLS group (142.77 g/L (SD: 11.79)) and the control group (139.05 g/L (SD: 12.33)) (t = 1.108, P > 0.05). Conclu-sions The decrease of serum ferritin may be a risk factor of primary restless legs syndrome, but the level of hemo-globin is not associated with primary restless legs syndrome.

Objective To evaluate the eyeball movement examination on Parkinson' s disease (PD) and investigate their vestibular function.Methods Thirty healthy volunteers and 55 PD patients served as subjects.Thirty-one patients had bradykinesia, 23 patients had resting tremor at first visit and 1 had both.Electronystagmogram examinations were performed in all the subjects.The eyeball movment gain (G) of PD group was compared with controls and the difference between the bradykinesia group and resting tremor group was analyzed.Dissymmetry of the bilateral pursuit movement was investigated.Results The eyeball movement gains decreased in PD patients (Left G 0.79±0.10, Right G 0.78±0.11) significantly (U = 394.500, t = 3.547, P < 0.01) compared with controls (Left G 0.86±0.05, Right G 0.85±0.06).There was no difference (t = -0.100,2.005, P0.05) between the bradykinesia group (Left G 0.79± 0.14,Right G 0.74±0.14) and the resting tremor group ( Left G 0.79±0.06,Right G 0.81±0.07).The dissymmetry of the bilateral movement increased significantly (U = 755.500, P < 0.05) in PD group (1.03±0.97) than in controls (0.87±0.86).Conclusion The velocity of the eyeball movement has decreased in patients with PD.There is no difference of the pursuit gain between bradykinesia group and the resting tremor group.The bilateral vestibular function is involved dissymmetrically.