OBJECTIVE: To evaluate the safety and clinical therapeutic effect of in-line mechanical in-exsufflation to assist sputum clearance in patients with invasive mechanical ventilation. METHODS: A prospective observational study was conducted at the department of critical care medicine, the First Affiliated Hospital of Sun Yat-sen University from April 2022 to May 2023. Patients who were invasively ventilated and treated with in-line mechanical in-exsufflation to assist sputum clearance were enrolled. Baseline data were collected. Sputum viscosity, oxygenation index, parameters of ventilatory function and respiratory mechanics, clinical pulmonary infection score (CPIS) and vital signs before and after day 1, 2, 3, 5, 7 of use of the in-line mechanical in-exsufflation were assessed and recorded. Statistical analyses were performed by using generalized estimating equation (GEE). RESULTS: A total of 13 invasively ventilated patients using in-line mechanical in-exsufflation were included, all of whom were male and had respiratory failure, with the main cause being cervical spinal cord injury/high-level paraplegia (38.46%). Before the use of the in-line mechanical in-exsufflation, the proportion of patients with sputum viscosity of grade III was 38.46% (5/13) and decreased to 22.22% (2/9) 7 days after treatment with in-line mechanical in-exsufflation. With the prolonged use of the in-line mechanical in-exsufflation, the patients' CPIS scores tended to decrease significantly, with a mean decrease of 0.5 points per day (P < 0.01). Oxygenation improved significantly, with the oxygenation index (PaO₂/FiO₂) increasing by a mean of 23.3 mmHg (1 mmHg ≈ 0.133 kPa) per day and the arterial partial pressure of oxygen increasing by a mean of 12.6 mmHg per day (both P < 0.01). Compared to baseline, the respiratory mechanics of the patients improved significantly 7 days after in-line mechanical in-exsufflation use, with a significant increase in the compliance of respiratory system (Cst) [mL/cmH₂O (1 cmH₂O ≈ 0.098 kPa): 55.6 (50.0, 58.0) vs. 40.9 (37.5, 50.0), P < 0.01], and both the airway resistance and driving pressure (DP) were significantly decreased [airway resistance (cmH₂O×L^-1×s^-1): 9.6 (6.9, 10.5) vs. 12.0 (10.0, 13.0), DP (cmH₂O): 9.0 (9.0, 12.0) vs. 11.0 (10.0, 15.0), both P < 0.01]. At the same time, no new lung collapse was observed during the treatment period. No significant discomfort was reported by patients, and there were no substantial changes in heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure before and after the in-line mechanical in-exsufflation treatment. CONCLUSIONS The combined use of the in-line mechanical in-exsufflation to assist sputum clearance in patients on invasive mechanical ventilation can effectively improve sputum characteristics, oxygenation and respiratory mechanics. The in-line mechanical in-exsufflation was well tolerated by the patients, with no treatment-related adverse events, which demonstrated its effectiveness and safety.
Humans ; Prospective Studies ; Respiration, Artificial/methods* ; Respiratory Insufficiency/therapy* ; Sputum

Objective·To investigate the regulatory effects and underlying mechanisms of mouse mandibular osteoblasts on B cell differentiation and development.Methods·Single-cell suspensions from mouse mandibular bone were prepared using an optimized enzymatic digestion method and induced to differentiate into osteoblasts in vitro.Osteogenic potential was validated by real-time quantitative PCR(RT-qPCR),alkaline phosphatase(ALP)staining,and alizarin red S(ARS)staining.The spatial localization relationship between osteoblasts and B cells in mandibular tissues was examined via immunofluorescence staining.High-purity hematopoietic progenitor cells were isolated using fluorescence-activated cell sorting.A Transwell co-culture system was established to assess the regulatory effects of different osteoblast concentrations(5×104,2.5×105,and 5×105 cells/well)on B cell differentiation(5×104 cells/well).Flow cytometry and RT-qPCR were employed to evaluate B cell viability and differentiation.Additionally,RT-qPCR was used to analyze the expression of osteoblast-secreted factors associated with B cell development during osteogenic differentiation.Results·Mandibular osteoblasts exhibited robust osteogenic potential,as confirmed by ALP/ARS staining and high expression of osteogenic markers(Runx2,Osx,Ocn,and Alp)via RT-qPCR.Immunofluorescence revealed close spatial proximity between osteoblasts and B cells in mandibular tissues.In the co-culture system,osteoblasts promoted B cell differentiation in a concentration-dependent manner.RT-qPCR and immunofluorescence demonstrated that osteoblasts significantly upregulated key genes involved in B cell development(Ebf1,Rag1,Il7r,and Pax5;all P<0.001).Furthermore,osteoblast-derived factors(Il7,Baff,and Flt3l)were markedly elevated during osteogenic differentiation(all P<0.05).Conclusion·Mandibular osteoblasts enhance B cell differentiation and development in a concentration-dependent manner,likely through secreting growth factors that upregulate critical B cell differentiation genes.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Objective:To investigate the efficacy of virtual simulation-guided unilateral locking plate combined with Jail screw technique for double column tibial plateau fractures involving the posterolateral plateau.Methods:A retrospective case series study was conducted to analyze the clinical data of 32 patients with double column tibial plateau fractures involving the posterolateral plateau admitted to Nanjing Drum Tower Hospital Group Suqian Hospital from March 2018 to March 2022, including 20 males and 12 females, aged 37-69 years [(47.5±6.9)years]. According to AO/OTA classification, the fractures were classified as type 41B in 17 patients and type 41C in 15. According to the three-column classification, the fractures were classified as lateral column+posterior column in 17 patients and medial column+posterior column in 15. Virtual simulation technique was used to simulate surgical operation before surgery. After reduction, the patients′ tibial plateau mirror models of the healthy side were used to simulate the implantation of internal fixators on the affected side. The position data of the placed internal fixators were obtained to guide the personalized treatment with unilateral locking plate combined with Jail screw technique. The total number of Jail screws, average number of Jail screws, distribution and accuracy of screw placement, operative duration, intraoperative blood loss, and fracture healing status were recorded. The posterior tibial plateau angle (PTSA), proximal medial tibial angle (MPTA) and Rasmussen anatomical score were compared before operation, at 1, 3, 6, 12 months after operation and at the last follow-up. The Lysholm scores at 6, 12 months after operation and at the last follow-up were used to evaluate the knee function. At the last follow-up, the knee range of motion was measured. Postoperative complications were observed.Results:All the patients were followed up for 28-36 months [(30.7±2.3)months]. The total number of Jail screws inserted was 48, with an average of (1.5±0.5) screws. In the sagittal direction, 1-2 Jail screws were inserted in each patient, with an accuracy rate of 88% (42/48). The operative duration was 78-116 minutes [(98.7±10.5)minutes]. The intraoperative blood loss was 70-120 ml [(96.6±15.6)ml]. All the fractures had healing of stage I, with a healing time of 4-7 months [(5.4±0.9)months]. At 1, 3, 6, 12 months after operation and at last follow-up, the PTSA, MPTA, and Rasmussen anatomical scores were significantly improved when compared with those before operation ( P<0.05), while there was no statistically significant difference between those at various postoperative time points ( P>0.05). The Lysholm knee scores were (83.6±3.9)points, (88.5±3.6)points, and (93.7±2.6)points at 6, 12 months after operation, and at the last follow-up, respectively, which were gradually increased with the passage of the follow-up time ( P<0.05). The range of motion was (121.4±4.6)° in flexion and was 0.0(0.0, 3.0)° in extension at the last follow-up. Two patients had superficial wound infection and 1 had wound dehiscence after operation, which recovered with dressing change or debridement and suturing. No deep infection, vascular injury or nerve damage occurred. Conclusions:The virtual simulation-guided unilateral locking plate combined with Jail screw technique has the advantages of high accuracy of screw placement, shorter operative duration, less intraoperative blood loss, satisfactory fracture reduction, favorable recovery of knee function and range of motion, and fewer postoperative complications in the treatment of double column tibial plateau fractures involving the posterolateral plateau.

Objective:To analyze the influencing factors of image quality of high-frequency ultrasound at the level of the glottis in healthy adults.Methods:A cross-sectional study was conducted on 433 healthy voluteers who underwent routine neck ultrasound examination at the Second Affiliated Hospital of Xi'an Jiaotong University from October 2023 to April 2024 and met the inclusion criteria. General data of the subjects were collected，and the image quality was graded. Gender，age，height，weight，body mass index，body surface area，thyroid cartilage calcification ratio，thickness of anterior cervical subcutaneous soft tissue and thickness of anterior cervical muscle group were analyzed by using multivariable Logistic regression for the influencing factors of image quality.Results:The display rates of the vocal cord epithelial layer and lamina propria，vocal cord muscle layer and paraglottic space structures in the para-thyroid cartilage section were superior to those in the anterior median section，with statistically significant differences（all P<0.05）. There were statistically significant differences in image quality grading among different age groups（all P<0.05），and image quality deteriorated as age increased. Logistic multivariate analysis indicated that gender，age and thyroid cartilage calcification ratio were independent factors affecting image quality（all P<0.05）. With age increased，thyroid cartilage calcification at the glottic level could be concentrated in the anterior，middle and posterior parts，respectively，and subsequently，calcification in the anterior and middle or middle and posterior parts gradually fused until complete calcification occurred. Conclusions:High-frequency ultrasound can clearly display the structures of most normal adult larynges at the glottis level，with the lateral section of the thyroid cartilage being superior to the median anterior neck section. As age increases，the degree of thyroid cartilage calcification increases，and image quality worsens.

Objective·To investigate the regulatory effects and underlying mechanisms of mouse mandibular osteoblasts on B cell differentiation and development.Methods·Single-cell suspensions from mouse mandibular bone were prepared using an optimized enzymatic digestion method and induced to differentiate into osteoblasts in vitro.Osteogenic potential was validated by real-time quantitative PCR(RT-qPCR),alkaline phosphatase(ALP)staining,and alizarin red S(ARS)staining.The spatial localization relationship between osteoblasts and B cells in mandibular tissues was examined via immunofluorescence staining.High-purity hematopoietic progenitor cells were isolated using fluorescence-activated cell sorting.A Transwell co-culture system was established to assess the regulatory effects of different osteoblast concentrations(5×104,2.5×105,and 5×105 cells/well)on B cell differentiation(5×104 cells/well).Flow cytometry and RT-qPCR were employed to evaluate B cell viability and differentiation.Additionally,RT-qPCR was used to analyze the expression of osteoblast-secreted factors associated with B cell development during osteogenic differentiation.Results·Mandibular osteoblasts exhibited robust osteogenic potential,as confirmed by ALP/ARS staining and high expression of osteogenic markers(Runx2,Osx,Ocn,and Alp)via RT-qPCR.Immunofluorescence revealed close spatial proximity between osteoblasts and B cells in mandibular tissues.In the co-culture system,osteoblasts promoted B cell differentiation in a concentration-dependent manner.RT-qPCR and immunofluorescence demonstrated that osteoblasts significantly upregulated key genes involved in B cell development(Ebf1,Rag1,Il7r,and Pax5;all P<0.001).Furthermore,osteoblast-derived factors(Il7,Baff,and Flt3l)were markedly elevated during osteogenic differentiation(all P<0.05).Conclusion·Mandibular osteoblasts enhance B cell differentiation and development in a concentration-dependent manner,likely through secreting growth factors that upregulate critical B cell differentiation genes.

Objective:To investigate the efficacy of virtual simulation-guided unilateral locking plate combined with Jail screw technique for double column tibial plateau fractures involving the posterolateral plateau.Methods:A retrospective case series study was conducted to analyze the clinical data of 32 patients with double column tibial plateau fractures involving the posterolateral plateau admitted to Nanjing Drum Tower Hospital Group Suqian Hospital from March 2018 to March 2022, including 20 males and 12 females, aged 37-69 years [(47.5±6.9)years]. According to AO/OTA classification, the fractures were classified as type 41B in 17 patients and type 41C in 15. According to the three-column classification, the fractures were classified as lateral column+posterior column in 17 patients and medial column+posterior column in 15. Virtual simulation technique was used to simulate surgical operation before surgery. After reduction, the patients′ tibial plateau mirror models of the healthy side were used to simulate the implantation of internal fixators on the affected side. The position data of the placed internal fixators were obtained to guide the personalized treatment with unilateral locking plate combined with Jail screw technique. The total number of Jail screws, average number of Jail screws, distribution and accuracy of screw placement, operative duration, intraoperative blood loss, and fracture healing status were recorded. The posterior tibial plateau angle (PTSA), proximal medial tibial angle (MPTA) and Rasmussen anatomical score were compared before operation, at 1, 3, 6, 12 months after operation and at the last follow-up. The Lysholm scores at 6, 12 months after operation and at the last follow-up were used to evaluate the knee function. At the last follow-up, the knee range of motion was measured. Postoperative complications were observed.Results:All the patients were followed up for 28-36 months [(30.7±2.3)months]. The total number of Jail screws inserted was 48, with an average of (1.5±0.5) screws. In the sagittal direction, 1-2 Jail screws were inserted in each patient, with an accuracy rate of 88% (42/48). The operative duration was 78-116 minutes [(98.7±10.5)minutes]. The intraoperative blood loss was 70-120 ml [(96.6±15.6)ml]. All the fractures had healing of stage I, with a healing time of 4-7 months [(5.4±0.9)months]. At 1, 3, 6, 12 months after operation and at last follow-up, the PTSA, MPTA, and Rasmussen anatomical scores were significantly improved when compared with those before operation ( P<0.05), while there was no statistically significant difference between those at various postoperative time points ( P>0.05). The Lysholm knee scores were (83.6±3.9)points, (88.5±3.6)points, and (93.7±2.6)points at 6, 12 months after operation, and at the last follow-up, respectively, which were gradually increased with the passage of the follow-up time ( P<0.05). The range of motion was (121.4±4.6)° in flexion and was 0.0(0.0, 3.0)° in extension at the last follow-up. Two patients had superficial wound infection and 1 had wound dehiscence after operation, which recovered with dressing change or debridement and suturing. No deep infection, vascular injury or nerve damage occurred. Conclusions:The virtual simulation-guided unilateral locking plate combined with Jail screw technique has the advantages of high accuracy of screw placement, shorter operative duration, less intraoperative blood loss, satisfactory fracture reduction, favorable recovery of knee function and range of motion, and fewer postoperative complications in the treatment of double column tibial plateau fractures involving the posterolateral plateau.

Objective:To analyze the influencing factors of image quality of high-frequency ultrasound at the level of the glottis in healthy adults.Methods:A cross-sectional study was conducted on 433 healthy voluteers who underwent routine neck ultrasound examination at the Second Affiliated Hospital of Xi'an Jiaotong University from October 2023 to April 2024 and met the inclusion criteria. General data of the subjects were collected，and the image quality was graded. Gender，age，height，weight，body mass index，body surface area，thyroid cartilage calcification ratio，thickness of anterior cervical subcutaneous soft tissue and thickness of anterior cervical muscle group were analyzed by using multivariable Logistic regression for the influencing factors of image quality.Results:The display rates of the vocal cord epithelial layer and lamina propria，vocal cord muscle layer and paraglottic space structures in the para-thyroid cartilage section were superior to those in the anterior median section，with statistically significant differences（all P<0.05）. There were statistically significant differences in image quality grading among different age groups（all P<0.05），and image quality deteriorated as age increased. Logistic multivariate analysis indicated that gender，age and thyroid cartilage calcification ratio were independent factors affecting image quality（all P<0.05）. With age increased，thyroid cartilage calcification at the glottic level could be concentrated in the anterior，middle and posterior parts，respectively，and subsequently，calcification in the anterior and middle or middle and posterior parts gradually fused until complete calcification occurred. Conclusions:High-frequency ultrasound can clearly display the structures of most normal adult larynges at the glottis level，with the lateral section of the thyroid cartilage being superior to the median anterior neck section. As age increases，the degree of thyroid cartilage calcification increases，and image quality worsens.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

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