Purpose: Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC. Materials and Methods: Seventy-five patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and preoperative and postoperative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients. Results: The tumor-informed fixed assay had a higher preoperative positive rate than the tumor-agnostic assay (73.3% vs. 57.3%). The preoperative ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined postoperative ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR], 20.74; 95% confidence interval [CI], 7.19 to 59.83; p < 0.001), which was an independent predictor by multivariable analysis (HR, 28.57; 95% CI, 7.10 to 114.9; p < 0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest preoperative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in postoperative landmark (HR, 26.34; 95% CI, 6.01 to 115.57; p < 0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04; 95% CI, 0.94 to 9.89; p=0.052). Conclusion Our study confirmed the prognostic value of the ctDNA positivity at postoperative day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.

Objective:To investigate the effect of tumor-associated macrophage(TAM) on proliferation of renal carcinoma cells and its related mechanism.Methods:The model of TAM was established by stimulating human monocytic leukemia cell line THP-1 with phorbol myristate acetate (PMA), bacterial endotoxin (LPS) and interferon-γ (IFN- γ). Then the TAM model was co-cultured with carcinoma cell lines ACHN and 786-O in vitro .The cytokines IL-6, TNF-α and IL-1β in TAM supernatant were detected by enzyme-linked immunosorbent assay (ELISA). MTT method was used to detect the proliferation of ACHN and 786-O cells treated with supernatant of TAM or TAM/Tocilizumab. Western blot was used to detect lactate dehydrogenase A (LDHA) expression of both renal cancer cells co-cultured with TAM or TAM/Tocilizumab. The ACHN and 786-O cells with LDHA-overexpression and LDHA-knockdown were cultured in TAM supernatant in vitro. The cell proliferation was detected by MTT and the relative proliferation rate was calculated.Results:THP-1 cells was differentiated into TAM through the treatment of 80 ng/ml PMA combined with 20 ng/ml LPS and 20 ng/ml IFN- γ.The expression rate of CD68, a cell surface marker on TAM, was (36.2 ±4.5)%. When TAM was co-cultured with ACHN cells, the results of ELISA showed that the secretion of IL-6 in the supernatant was significantly elevated compared with that in the supernatant when ACHN cells cultured alone [(138.0 ±12.4) pg/ml and (19.7±4.9) pg/ml], and the secretion of TNF- α [(122.5 ±14.2) pg/ml and (12.6 ±2.3) pg/ml] and IL-1 β [(89.2 ±6.4) pg/ml and (69.2 ±3.5) pg/ml] were also significantly increased. The secretion of IL-6 [(119.2 ±14.8) pg/ml and (17.1 ±3.3) pg/ml], TNF- α [(122.6 ±14.4) pg/ml and (45.7 ±7.2) pg/ml] and IL-1 β [(95.1 ±11.8) pg/ml and (88.2 ±12.7) pg/ml] in the supernatant were also significantly elevated when 786-O cells co-cultured with TAM compared with 786-O cells cultured alone. After treated with the supernatant of TAM for 72 hours, the relative proliferation rates of ACHN and 786-O cells [(128.6 ±21.4)% and (124.2 ±19.7)%] were significantly higher than that of the control group (100.0%). At the same time, the expression of LDHA in ACHN and 786-O cells increased significantly. After 72 hours of treatment with the supernatant of TAM combined with tocilizumab, the relative proliferation rates of ACHN and 786-O cells [(76.5±13.7)% and (74.8±12.5)%] were significantly lower than that of the control group(100.0%), and the expression of LDHA was also significantly decreased at the same time. The relative proliferation rates of ACHN and 786-O cells in LDHA overexpression group [(121.5 ±17.2)% and (122.7±21.6)%]were significantly higher than that in blank-vector-transfection group[(93.3±10.7)% and (89.8±11.2)%], while the relative proliferation rates in LDHA-knockdown group [(61.4±11.2)% and (58.0 ±10.6)% ]were significantly lower than that in blank-vector-transfection group.Conclusions:By secreting IL-6, TAM can up-regulate the expression of LDHA and promote the proliferation of renal cancer cells.

Primary liver cancer (PLC) is one of the most common malignant tumors with characteristics of strong invasiveness and poor prognosis. The morbidity and mortality of PLC rank among the top malignant tumors in the world. More than half of the world′s liver cancer occurs in China, which seriously threatens the health and life of Chinese people. Due to the imperceptible initial symptoms, most patients are not diagnosed until their tumors have progressed to be in advanced stage, and lose the chance for curative hepatectomy. At present, non-surgical treatment options, including interventional embolization, ablation, radiotherapy, chemotherapy, and systemic chemotherapy, play an increasingly prominent role in the comprehensive treatment of liver cancer. The authors briefly review the current status and research progress of the non-surgical treatment for liver cancer.

Objective:To investigate the epidemiological characteristics and influencing factors of scoliosis among primary and middle school students in Dali Bai autonomous prefecture.Methods:A total of 176,729 students aged 6-18 years from 380 primary and secondary schools in eight counties of Dali Bai Autonomous Prefecture were screened for spinal health by visual method, Adams forward bend test and scoliometer measuring the angle of trunk rotation from September to November 2021. The angle of trunk rotation ≥5° or visual method retest positive was used as a positive standard to confirm suspected scoliosis population. Demographic data of the screening population including name, gender, age and ethnicity were collected. The average altitude of the community or village committee in the screening area was recorded. Binary logistic regression analysis was used to screen the influencing factors of scoliosis.Results:There were 176,729 people planned to complete the screening. A total of 140,026 people were actually completed screening with completion rate 79.23%. A total of 3,190 (2.28%) suspected scoliosis positive people were detected. The detection rate of female was 2.52%, which was higher than that of male 2.03% (χ 2=37.18, P<0.001). The detection rate of 10-18 years old group was 2.90%, which was higher than that of 6-9 years old group 0.70% (χ 2=620.79, P<0.001). There was a significant difference in the detection rate among different age groups from 6 to 18 years old (χ 2=1,451.00, P<0.001). The detection rate of Han population was 2.67%, which was higher than that of non-Han population 2.15% (χ 2=31.06, P<0.001). In non-Han population, the detection rate of Bai population was 2.07%, which was lower than that of non-Bai population 2.26% (χ 2=4.02, P=0.045). Trend chi-square test showed significant difference in the detection rate of scoliosis among the general population, 10-18 years old population and 6-9 years old population in the altitude <1,500 m, 1,500-1,599 m, 1,600-1,699 m, 1,700-1,799 m, 1,800-1,899 m, 1,900-1,999 m, 2,000-2,099 m, 2,100-2,199 m, 2,200-2,299 m and ≥2,300 m groups (χ 2=249.02, 195.64, 24.46, P<0.05). Binary logistic regression analysis showed that the risk of scoliosis was lower in males than that in females ( OR=0.82, P<0.001). The risk of scoliosis was increased in 10-18 years old compared with that in 6-9 years old ( OR=0.12, P<0.001). The risk of scoliosis was low in Bai population compared with that in Han populations ( OR=0.75, P<0.001). The altitude ≥2,000 m was a risk factor ( OR=1.52, P<0.001). Conclusion:The detection rate of suspected scoliosis in primary and middle school students in Dali Bai Autonomous Prefecture was 2.28%. Female, aged 10-18 years, Han populations, and residence in altitude ≥2,000 m might be the risk factors for scoliosis.

ObjectiveTo provide a new idea for exploring the molecular genetic approach to the pathogenesis of schizophrenia via construction of microRNA-messenger RNA （miRNA-mRNA） regulatory network in schizophrenia. MethodsThe microarray datasets of GSE54578 miRNA expression profiles in peripheral blood and GSE145554 mRNA expression in the anterior cingulate in postmortem brain of schizophrenic subjects were downloaded from Gene Expression Omnibus （GEO） database since July 2021. The GEO2R was used to identify the differentially expressed miRNAs and mRNAs， screen the miRNA with target differentially expressed mRNA， and predict their potential upstream transcription factors. The overlapping genes from the mRNA targeted by the differentially expressed miRNA and the mRNA differentially expressed in GSE145554 dataset were collected. Then the biological features of hub genes were analyzed via Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis， and the protein-protein interaction （PPI） network and miRNA-mRNA regulatory network of hub genes were constructed. ResultsA total of 8 up-regulated differentially expressed miRNAs with targeted mRNA were screened out in GSE54578 datasets regarding schizophrenia， which involved in the regulation of 10 transcription factors， 247 down-regulated differentially expressed mRNAs were screened out in GSE145554 datasets， and 17 overlapping mRNAs were obtained. GO analysis showed that the target mRNAs were mainly involved in astrocyte differentiation and development. KEGG pathway enrichment analysis showed that the target mRNAs were mainly involved in Rap1 and Ras signaling pathways. PPI network analysis showed that the mRNAs （KRAS and CD28） might be key genes in schizophrenia. ConclusionThe integrated bioinformatics analysis based on GEO database can identify potential susceptibility genes in schizophrenia， and it also contributes to the construction of miRNA-mRNA regulatory network in schizophrenia.

Objective : To investigate the expression levels and potential clinical significance of pre-B-cell leukemia homologous box 3 (PBX3) in bone marrow samples from acute myeloid leukemia (AML) . Methods : The mRNA expression levels of PBX3 were determined by bioinformatics which analyzed the RNAseq data of 33 malignancies from the cancer genome atlasdatabase． (TCGA) The correlations among the expression levels of PBX3，the clinical parameters and prognosis of AML patients were further analyzed．The differentially expressed genes in the whole transcriptome were analyzed to identify the molecular network in AML caused by PBX3 expression abnormalities. Results : The mRNA expression levels of PBX3 were up-regulated in 12 malignancies，and the altitudes increased most significantly in AML than any other cancer types．Patients with high PBX3 expression showed shorter overall survival and disease-free survival than patients with low PBX3 expression．High PBX3 expression was significantly associated with FLT3，NPM1，and DNMT3A mutation．PBX3 expression was positively correlated with multiple ho- meobox genes (including most HOXA and HOXB genes ，MEIS1 ) ，and the expression levels of these homeobox genes were all negatively correlated with AML patients overall survival． Conclusion PBX3 high expression in the bone marrow of AML patients is a potential biomarker for poor prognosis ，and it may have extensive interactions with other homeobox genes.

Objective: To explore the efficacy of open reduction and internal fixation in the treatment of senile osteoporotic ankle fractures. Methods: A retrospective case series study was conducted to analyze the data of 26 elderly patients with osteoporotic ankle fractures which all caused by sprain from June 2012 to June 2018 in Changhai Hospital, including 10 male and 16 female patients aged from 60 to 93 years (mean, 69.72 years). In these 26 patients, three had medial malleolus fractures, four had lateral malleolus fractures, six had double ankle fractures and 13 had cotton's fractures. According to the Lauge-Hansen type, all 26 patients can be classified into four types: 5 with supination external rotation type, 4 supination adduction type, 16 with pronation-external rotation type and 1 with pronation abduction type. All the patients received open reduction and internal fixation. Plate fixation was used for lateral and posterior malleolus fractures, plate fixation and cannulated screws were applied to fix the comminuted posterior malleolus fracture while in the comminuted internal malleolus fracture, the steel plate was used only when needed. Early professional functional rehabilitation training and active anti-osteoporosis treatment were applied. All the operation time and bleeding volume were recorded, and the reduction of fracture plus the healing of wounds were observed. At last follow-up, American Orthopedic Foot & Ankle Society (AOFAS) Ankle Hindfoot Scale was used to evaluate the treatment effect and the Visual Analogue Scale (VAS)to evaluate the therapeutic effect and the subjective satisfaction of the patients. Complications were recorded as well. Results: All patients were followed up for 12-48 months (mean, 23.6 months). Operation time ranged from 30 to 95 minutes (mean, 70 minutes) and bleeding volume ranged from 10 to 150 ml (mean, 70 ml). All patients got satisfied reduction of fracture within 25 patients' incision healing in first intention, although one has fat liquefaction. AOFAS Ankle Hindfoot Scale improved from preoperative (84.4±10.8)points to (31.9±11.4)points at last follow-up (P<0.01), and the results were excellent in five patients, good in 17, fair in three and poor in one, with the excellent and good rate of 85%. VAS improved from preoperative(1.85±0.73)points to (9.23±0.28)points at last follow-up (P<0.01). Among 26 patients, 5 with ankle stiffness of different degree recovered after rehabilitation care, and 2 with internal malleolus fractures had bone displacement when receiving rehabilitation care, with no side effect on basic function. No serious complications such as wound infection or skin necrosis were found. Conclusion For osteoporotic ankle fractures in the elderly, open reduction and internal fixation can promote functional recovery and relieve pain.

In the nucleus, chromatin is folded into hierarchical architecture that is tightly linked to various nuclear functions. However, the underlying molecular mechanisms that confer these archi-tectures remain incompletely understood. Here, we investigated the functional roles of H3 lysine 9 dimethylation (H3K9me2), one of the abundant histone modifications, in three-dimensional (3D) genome organization. Unlike in mouse embryonic stem cells, inhibition of methyltransferases G9a and GLP in differentiated cells eliminated H3K9me2 predominantly at A-type (active) genomic compartments, and the level of residual H3K9me2 modifications was strongly associated with B-type (inactive) genomic compartments. Furthermore, chemical inhibition of G9a/GLP in mouse hepatocytes led to decreased chromatin-nuclear lamina interactions mainly at G9a/GLP-sensitive regions, increased degree of genomic compartmentalization, and up-regulation of hundreds of genes that were associated with alterations of the 3D chromatin. Collectively, our data demonstrated essential roles of H3K9me2 in 3D genome organization.

Objective: To study the correlation between pancreatic duct stent placement and postoperative pancreatic fistula in patients undergoing pancreaticoduodenectomy. Methods: We performed a retrospective review on 298 patients who underwent pancreaticoduodenectomy from Jan 2011 to Dec 2016. Patients were divided into none stent group, external stent group and internal stent group according to the placement and drainage of the pancreatic duct stent. Results: There were 60 cases in none stent group, 103 cases in external stent group and 135 cases in internal stent group. Altogether there were 52 cases suffering from biochemical pancreatic fistula, 52 cases of grade B fistula and 9 cases of grade C pancreatic fistula. There were three factors with statistical significance: 1, the operative method (χ²=20.947, P=0.000), 2, the diameter of main pancreatic duct (χ²=8.662, P=0.013), and 3, the intraoperative blood loss (χ²=14.03, P=0.001). There were no statistical significance difference between no stenting group and external/ internal stent group in the incidence of pancreatic fistula (P>0.05). The difference between internal stent group and external stent group was of statistical significance (χ²=9.948, P=0.019). The incidence of clinically relevant pancreatic fistula in external stent group was lower than the internal stent group (14.5% vs. 26.6%)(χ²=9.777, P=0.002). Conclusions The pancreatic duct stenting is not a risk factor for pancreatic fistula. The external drainage of pancreatic juice is associated with a lower incidence of pancreatic fistula compared to the internal drainage.