Mutational Signatures Analysis of Micropapillary Components and Exploration of ZNF469 Gene in Early-stage Lung Adenocarcinoma with Ground-glass Opacities / 中国肺癌杂志

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.

Comparison of minimally invasive reduction through a bone tunnel combined with Jail screwing and posterolateral locking plating for simple posterolateral tibial plateau fractures / 中华创伤骨科杂志

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.

Proximal tibial lateral locking plate with rafting screws combined with Jail screws in the treatment of collapse fracture of the lateral tibial plateau / 中华创伤杂志

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.

Inhibitory effect of ketogenic diet on neuroblastoma in BALB/c-nu mouse models / 南方医科大学学报

OBJECTIVE@#To investigate the inhibitory effect of ketogenic diet (KD) on growth of neuroblastoma in mice.@*METHODS@#BALB/c-nu mouse models bearing neuroblastoma xenografts were established by subcutaneous injection of human neuroblastoma cell line (SH-SY5Y). When the tumor volume reached 250 mm3, the mice were randomized into SD group with standard diet and PBS treatment, KD group with ketogenic diet and PBS treatment, and CP+KD group with ketogenic diet and cyclophosphamide (60 mg·kg·day) treatment, =8. The tumor volume, body weight, blood glucose, ketone body (β-Hydroxybutyrate) levels, and hepatic steatosis in the mice were assessed. The expressions of caspase-3 and caspase-8 were detected by Western blotting, and Ki67 expresison was detected using immunohistochemistry (IHC). Transmission electron microscopy (TEM) was employed for the autophagosomes, and the autophagic protein Beclin1, LC3A/B and P62 were detected by IHC and Western blotting.@*RESULTS@#On day 28 post tumor cell injection, the mice in KD and CP+KD groups could prolong the overall survival rates than that in SD group ( < 0.001). On day 22 post the injection, the tumor volume in KD group was smaller than that in SD group ( < 0.05); on 16, 19, and 22 day post the injection, the tumor volume in CP+KD group was smaller than that in SD group ( < 0.01). The mice in SD group showed greater body weight on day 19 and higher blood glucose level on day 13 post the injection than those in the other two groups ( < 0.05). Blood ketone level and hepatic steatosis score were higher and glucose ketone index (GKI) was lower in KD and CP+KD groups than those in SD group (all < 0.05). The expressions of Ki67 and apoptotic proteins were detected in the tumor tissues of all groups. TEM revealed more autophagosomes in the tumor tissues of KD group than that of SD group. P62 expression was lowered ( < 0.01) and Beclin1 and LC3A/B expressions were up-regulated in the tumor tissues of KD group ( < 0.05), which is consisitent with IHC.@*CONCLUSIONS@#KD has a strong anti-tumor effect in the xenograft mouse model possibly by regulating cell autophagy.

Efficacy and safety of 125Iseed implantation for treating neuroblastoma in nude mice / 中华放射肿瘤学杂志

Objective To examine the efficacy and safety of 125Iseed implantation for treating neuroblastoma (NB) in animal models.Methods A total of 45 nude mice models of neuroblastoma were constructed and divided into the 125Igroup.control group.and blank group at 15 mice per group.The long and short diameters of the tumor were measured every 3 days.and the tumor inhibition rate was calculated every 9 days.Apoptotic and proliferative protein expression levels in tumor tissue and peritumoral tissue.as well as endocrine markers and bone marrow of the nude mice.were analyzed.The independent sample t test was used to compare the mean scores.and ANOVA was used for comparison between multiple groups.Results Tumor volume inhibition rate was significantly higher in the 125Igroup than in the control group and blank group on days 9.18.and 27(all P0.05).In addition.no significant difference in the expression of Caspase-3 and PCNA in peritumoral tissue was observed between the 125Igroup.control group.and blank group (all P>0.05).Cell apoptosis in tumor tissue was significantly lower in the blank group and control group than in the 125Igroup (all P0.05).There was no significant difference in endocrine markers between the three groups (P>0.05).There was no significant bone marrow suppression in the 125Igroup.and this observation was similar to those in the control group and blank group (all P>0.05).Conclusions 125Iseeds have significant toxicity to NB.125Iseed implantation is safe in nude mice with NB within the therapeutic doses.

Femoral head-neck ratio in patients with Cam-type femoroacetabular impingement and healthy adults and its impact on surgical strategy / 中华骨科杂志

Objective To explore the difference of the femoral head-neck ratio (FHNR) in patients with Cam-type femoroacetabular impingement (FAI) and healthy adults and its impact on surgical strategy.Methods We measured the FHNR using method described by Doherty.468 healthy adults without hip symptoms acted as controls in the study,including 313 males and 155 females,with the mean age of 42.4years (range,17-82 years).There were 17 patients (24 hips) in the Cam-type FAI group.The maximum diameter of the femoral head and the minimum vertical diameter of femoral neck on both sides were measured by Digimizer software on the standard anteroposterior pelvis film.The ratio of femoral head to femoral neck was calculated and was compared.The surgery was performed in 7 cases (8 hips) with FAI.The Harris score and internal rotation angle was also compared.Results The FHNR of control group and Cam-type FAI group was 1.48±0.09(1.33-1.69) and 1.30±0.13 (1.01-1.46) separately (P＜0.01).The volume of osteophyte removed during operation was related with the FHNR.The average Harris score had improved from 63.4±8.2(52-76) preoperatively to 89.2±3.5(84-95) postoperatively.The average internal rotation angle had improved from 2.5°±2.7°(0°-5°) preoperatively to 12.5±3.8°(5°-15°) postoperatively.Conclusion FHNR measurement is useful for the diagnosis and surgical treatment of Cam-type FAI.

The measurement of femoral head-neck ratio and its clinical significance in Chinese / 中华骨科杂志

Objective To measure the femoral head-neck ratio among Chinese adults in Nanjing to explore its clinical significance. Methods 468 Chinese without hip symptoms were chosen randomly. There were 313 males and 155 females. 13 cases were less than 20 years old, 88 cases were from 21 to 30 years old, 123 cases were from 31 to 40 years old, 104 cases were from 41 to 50 years old, 102 cases were from 51 to 60 years old, 24 cases were from 61 to 70 years old, 14 cases were more than 71 years old. The mean age was 42.4 years old (ranged from 17 to 82 years old). The maximum diameter of the femoral head and the minimum vertical diameter of femoral neck length on both sides were measured by Digimizer software in the standard anteroposterior pelvis film. The femoral head-neck ratio (FHNR) was calculated and compared with that of the western. Results The normal FHNR of Chinese in Nanjing was 1.48 ± 0.09 (1.33-1.69). FHNR was 1.46±0.09 in Chinese aged less than 20 years old. It was 1.48±0.09 in Chinese aged from 21 to 30 years, and 1.47±0.10 in those aged 31-40 years, 1.46±0.09 in 41-50 years, 1.49±0.10 in 51-60 years,1.48±0.08 in 61-70 years, 1.49±0.10 in those more than 71 years. There was no difference between male and female, the left and right side or the different age groups. There was no difference between the western and Chinese in Nanjing. Conclusion FHNR measurement has not variation with regard to sex, age and side. It may be useful to understand some kind of the hip diseases.

Effect of BRL-37344 on ion channel in guinea pig cardiac myocytes / 第三军医大学学报

Objective To study the biological effect of ?3 adrenoceptor-activated electrophysiological activities in cardiac myocytes. Methods Changes of transient outward potassium ( Ito) and L-type calcium current ( ICa-L) in primary cultured guinea pig cardiacmyocytes were detected with the standard whole-cell patch clamp technique about 5 -10 min before and after administration of ?3 adrenoceptor agonist,4--2-hydroxy-( 3-chlorophenyl) ethyl-aminopropylphenoxyacetate ( BRL-37344; BRL). Results BRL could significantly increased the Ito in guinea pig cardiac myocytes with the I-V curve up-moved. When the membrane potential reached to + 80 mV,the density current increased from 6. 11 ? 1. 03 pA/pF to 8. 46 ? 2. 07 pA/pF ( n = 6,P =0. 013 064). BRL ( 10 -6mol/L) could significantly increase the ICa-Lin guinea pig cardiac myocytes,which was ( 2. 30 ?0. 75) -fold higher than in control group( n =5,P =0. 0063). When the membrane potential increased to + 10 mV ,the current,increased from 89. 25 ? 17. 83 pA to 205. 00 ? 72. 24 pA ( n = 5,P = 0. 006 3). Conclusion BRL-37344 can increase the transient Itoand ICa-L,thus further regulating the cardiac activities.