Objective To examine the application of On-Board Imaging (OBI) system-based image-guided radiotherapy (IGRT) in the improvement of the precision of intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma.Methods Ten patients with nasopharyngeal carcinoma were treated with IMRT using the OBI system. The IGRT images after positioning, position adjustment, and treatment were observed and recorded to investigate the image difference between CT simulation and IGRT. Results The deviations in the x (lateral), y (cranial-caudal), and z (ventral-dorsal) directions between CT simulation and IGRT images were 0.22±1.00 mm,-0.37±1.28 mm, and 0.04±1.36 mm, respectively, after positioning, 0.29±0.76 mm,-0.04±0.78 mm, and -0.01±0.92 mm, respectively, after position adjustment, and 0.20±0.78 mm, 0.16±0.80 mm, and 0.05±0.92 mm, respectively, after treatment. The probabilities of a ≤1 mm deviation in the x, y, and z directions were 81.0%, 77.6%, and 88.2%, respectively, after positioning, 92.5%, 96.4%, and 96.4%, respectively, after position adjustment, and 91.7%, 94.9%, and 96.8%, respectively, after treatment. Conclusions The application of OBI system-based IGRT is very important in the improvement of the precision of fractionated IMRT for patients with nasopharyngeal carcinoma. The position of the patient should be adjusted based on the IGRT image after positioning in order to correct set-up error and effectively increase the precision of fractionated IMRT.

Objective: To compare the efficacy of induction chemotherapy with or without autologous hematopoietic stem cell transplantation (auto-HSCT) for newly diagnosed young diffuse large B cell lymphoma (DLBCL) patients. Methods: The retrospective study was performed in 90 cases of young patients (≤60 years) with newly diagnosed DLBCL and an age-adjusted International Prognostic Index (aa-IPI) score of 2 or 3. All of them were treated with R-CHOP (32 cases, rituximab combined with CHOP), dose-intensive regimens (DA-EPOCH, Hyper CVAD/MA or ESHAP) combined with or without rituximab (25 cases), and consolidated with up-front auto-HSCT (33 cases), respectively. The efficacy and the potential predictors were evaluated. Results: ①The median age of 90 patients was 43 (18-60) years old. The median follow-up time was 42 (3-110) months. ②The 5-year progression-free survival (PFS) for R-CHOP group, dose-intensive chemotherapy group and auto-HSCT group were (33.5±10.7) %, (55.3±10.1) % and (65.8±13.6) % (P=0.012), the 5-year overall survival (OS) were (49.7±9.0) %, (61.6±10.2) % and (78.6±7.8) % (P=0.035), respectively. There was no significant difference in 5-years PFS and OS between the R-CHOP group and dose-intensive chemotherapy group (P=0.519, P=0.437) compared with that of the dose-intensive chemotherapy group, auto-HSCT group has higher 5-year PFS (P=0.042). ③ When stratified with IPI score, the high-risk group treated with auto-HSCT (26 cases) showed similar 5-years PFS and 5-years OS to those in the low-risk group with chemotherapy alone (12 cases were in R-CHOP group and 8 cases were in dose-intensive chemotherapy group) [5-years PFS were (62.3 ±14.3)%, (58.3 ±18.6)% and (51.4±18.7)%, respectively, P=0.686; 5-years OS were (69.2±13.9)%, (62.5±15.5)% and (58.3±18.6)%, respectively, P=0.592]. ④However, the high-risk group treated with auto-HSCT (26 cases) showed superior 5-years PFS (P=0.002) and 5-years OS (P=0.019) compared to the high-risk group with chemotherapy alone (20 cases were in R-CHOP group and 17 cases were in dose-intensive chemotherapy group) [5-years PFS were (62.3±14.3)%, (41.1±13.5)% and (21.9±11.6)%, respectively; 5-years OS were (69.2±13.9)%, (51.5%±14.0)% and (35.4±13.6)%, respectively]. ⑤In the univariate analysis, as a whole, patients diagnosed with GCB subtype had higher 3-years PFS (P=0.022) and 3-years OS (P=0.037) compared to non-GCB subtype patients; in subgroup analysis, patients diagnosed with GCB subtype had higher 3-years PFS and 3-years OS compared to non-GCB subtype both in R-CHOP group (P=0.030, P=0.041) and dose-intensive chemotherapy group (P=0.044, P=0.047), but not in auto-HSCT group (P=0.199, P=0.093). ⑥In the multivariate analysis, different molecular classification (GCB/non-GCB) was an independent predictor for PFS and OS both in R-CHOP group [HR=0.274 (95% CI 0.094-0.800), P=0.018; HR=0.408 (95% CI 0.164-1.015), P=0.045] and dose-intensive chemotherapy group [HR=0.423 (95% CI 0.043-1.152), P=0.048; HR=5.758 (95% CI 0.882-6.592), P=0.035]. However, there was no significant difference in PFS and OS for auto-HSCT group between GCB/non-GCB patients. Conclusion Induction chemotherapy followed by up-front auto-HSCT has significant effect on efficacy for young and untreated patients with high risk DLBCL. Combined with induction chemotherapy followed by up-front auto-HSCT could improve the prognosis of non-GCB patients.

OBJECTIVE: To retrospectively analyze the clinical phenotypes and genetic variants in two Chinese pedigrees affected with Hereditary hypofibrinemia (IFD) and explore their molecular pathogenesis. METHODS: Two probands and their pedigree members were admitted to the First Affiliated Hospital of Wenzhou Medical University on March 30, 2021 and May 27, 2021, respectively. Clinical phenotypes of the probands were collected, and blood clotting indexes of the probands and their pedigree members were determined. Variants of the FGA, FGB and FGG genes were analyzed by Sanger sequencing, and candidate variants were verified by sequence comparison. Bioinformatic software was used to analyze the conservation of the amino acids and pathogenicity of the proteins. Alteration in protein structure and intermolecular force before and after the variant was analyzed by simulating the protein model. RESULTS: Proband 1, a 18-year-old male, had significantly low plasma fibrinogen activity (Fg:C) and plasma fibrinogen antigen (Fg:Ag), respectively at 0.80 g/L and 1.00 g/L. Proband 2, a 43-year-old male, had slightly low Fg:C and Fg:Ag at 1.35 g/L and 1.30 g/L, respectively. The Fg:C and Fg:Ag of proband 1's father, proband 2's father and son were also below the normal level. Genetic testing showed that proband 1 had harbored a heterozygous missense variant of c.688T>G (p.Phe230Val) in exon 7 of the FGG gene, which was inherited from his father. Proband 2, his father and son all had harbored a heterozygous variant of c.2516A>C (p.Asn839Thr) in exon 6 of the FGA gene. Homology analysis showed that the Phe230 and Asn839 residues were highly conserved among homologous species. Bioinformatic analysis predicted that both p.Phe230Val and p.Asn839Thr were pathogenic variants. CONCLUSION Analysis of protein simulation model showed that the p.Asn839Thr variant has changed the hydrogen bo`nd between the amino acids, thus affecting the stability of the protein structure. The heterozygous missense variants of p.Phe230Val and p.Asn839Thr probably underlay the IFD in the two pedigrees.
Humans ; Male ; Amino Acids ; East Asian People ; Exons ; Pedigree ; Retrospective Studies ; Afibrinogenemia/genetics* ; Mutation, Missense ; Fibrinogen/genetics*

Objective:To analyze the effects of different dose calculation grid size of Monaco system on the physical and biological dosimetry of target area and organ at risk (OAR) in T 4 nasopharyngeal carcinoma. Methods:A total of 18 patients with stage T 4 nasopharyngeal carcinoma who received radiotherapy in the Department of Radiotherapy of Yunnan Cancer Hospital from October 2020 to April 2022 were selected to complete the delineation of target areas and OAR in the Monaco 5.11.03 system, and the volumetric intensity modulated arc therapy (VMAT) plan was developed on the 3 mm grid with the optimization mode of target area priority. The 3 mm grid group plan was replicated without changing any other parameters, and the physical plan was re-established on the 1, 2, 4 and 5 mm grids, and then the five plans were normalized to the prescription dose to cover 95% of the target volume. The planning time, D 2%, D 50%, D 98%, conformity index (CI), homogeneity index (HI), gradient index (GI), tumor control probability (TCP), D 2% and D mean of important OAR around the target area were calculated and statistically analyzed. Results:Planning primary tumor gross target volume (PGTVp) : The D 2% of 1, 2, 3, 4 and 5 mm groups were (76.94±0.66), (75.98±0.76), (75.56±0.67), (75.67±0.73) and (75.94±0.85) Gy, respectively, with a statistically significant difference ( F=9.86, P<0.001). The CI of 1, 2, 3, 4 and 5 mm groups were 0.75±0.05, 0.78±0.04, 0.78±0.05, 0.79±0.04 and 0.78±0.04, respectively, with a statistically significant difference ( F=2.61, P=0.041). There were statistically significant differences in D 50%, D 98%, HI, equivalent uniform dose (EUD) and tumor control probability (TCP) among the groups ( H=17.14, P=0.002; F=9.35, P<0.001; H=25.43, P<0.001; F=5.85, P<0.001; H=17.65, P=0.001). There was no statistically significant difference in GI among the groups ( P>0.05). Pairwise comparison showed that D 2% in 2, 3, 4, 5 mm groups compared with 1 mm group, D 50% in 5 mm group compared with 2, 3 mm groups, D 98% in 4 mm group compared with 1, 2 mm groups, D 98% in 5 mm group compared with 1, 2, 3 mm groups, CI in 5 mm group compared with 1 mm group, HI in 2, 3, 4, 5 mm groups compared with 1 mm group, EUD in 3 mm group was compared with 1 mm group, EUD in 5 mm group compared with 2, 3 mm groups, TCP in 3 mm group compared with 1 mm group, and TCP in 5 mm group compared with 3 mm group, there were statistically significant differences (all P<0.05). Planning nodal gross target volume (PGTVn) : The D 2% of 1, 2, 3, 4 and 5 mm groups were (76.36±0.59), (75.36±0.62), (75.04±0.68), (75.25±0.72) and (75.39±0.77) Gy, respectively, with a statistically significant difference ( F=10.32, P<0.001). The HI of 1, 2, 3, 4 and 5 mm groups were 1.08 (1.08, 1.08), 1.07 (1.06, 1.07), 1.06 (1.06, 1.07), 1.06 (1.06, 1.07), 1.06 (1.06, 1.07), 1.06 (1.06, 1.08), respectively, with a statistically significant difference ( H=22.00, P<0.001) ; There were statistically significant differences in D 50%, D 98% and EUD among the groups ( H=11.79, P=0.019; H=20.49, P<0.001; F=12.14, P=0.016). Pairwise comparison showed that there were statistically significant differences in D 2% between 2, 3, 4, 5 mm groups and 1 mm group, D 98% between 4 mm group and 1 mm group, D 98% between 5 mm group and 1, 2 mm groups, HI between 2, 3, 4 mm groups and 1 mm group, and EUD between 3 mm group and 1 mm group (all P<0.05). Planning primary tumor clinical target volume 1 (PCTVp1) : The D 2% of 1, 2, 3, 4 and 5 mm groups were (76.59±0.63), (75.64±0.65), (75.64±0.98), (75.41±0.70) and (75.71±0.84) Gy, respectively, with a statistically significant difference ( F=9.53, P<0.001). The D 50% of 1, 2, 3, 4, 5 mm groups were (72.09±0.34), (71.85±0.39), (71.82±0.45), (72.04±0.56), (72.43±0.66) Gy, respectively, with a statistically significant difference ( F=4.20, P=0.019). There was no statistically significant difference in the other indexes among the groups (all P>0.05). Pairwise comparison showed that there were statistically significant differences in D 2% between 2, 3, 4, 5 mm groups and 1 mm group, and in D 50% between 2, 3 mm groups and 1 mm group (all P<0.05). Planning nodal clinical target volume 1 (PCTVn1) : There were no statistically significant differences in all indexes among the groups (all P>0.05). Planning clinical target volume 2 (PCTV2) : The D 2% of 1, 2, 3, 4 and 5 mm groups were (75.57±0.50), (74.87±0.67), (74.51±0.51), (74.61±0.63) and (75.00±0.74) Gy, respectively, with a statistically significant difference ( F=8.27, P<0.001). Pairwise comparison showed that the D 2% of the 2, 3, 4 mm groups were significantly different from that of the 1 mm group (all P<0.05). The calculation time of physical plan in 1, 2, 4 and 5 mm groups was 987.00 (848.00, 1 091.00), 120.50 (99.75, 134.00), 26.00 (24.00, 34.25) and 21.50 (18.75, 34.75) s, respectively, with a statistically significant difference ( H=61.62, P<0.001). Pairwise comparison showed that there were statistically significant differences in the calculation time between 4 mm group and 1, 2 mm groups, 5 mm group and 1, 2 mm groups (all P<0.05). There was no statistically significant difference in the dosimetric parameters of OAR around the target area among the groups (all P>0.05) . Conclusion:The physical dose and biological dose of the important OAR around the target area and the target area change with the change of dose calculation grid size when formulating the physical plan of radiotherapy for T 4 nasopharyngeal carcinoma. Considering the quality of the physical plan and the calculation time, when the Monaco system formulates the VMAT plan for T 4 nasopharyngeal carcinoma patients, the plan can be optimized on the 3 mm computing grid and copied to the 1 mm computing grid for recalculation.

Objective:To investigate whether long non-coding RNA(lncRNA) AW112010 can improve insulin resistance in aging adipocytes through the miR-204/POU2F2 signaling pathway.Methods:In vivo experiment: C57BL/6 mice were divided into young control group(4 months old) and aging model group(18 months old) based on body weight. The expression levels of AW112010, miR-204-5p, POU2F2, aging related indicators(p16, p21), and insulin signaling pathway genes [insulin receptor(INSR), insulin receptor substrate 1(IRS1), phosphatidylinositol kinase(PI3K), protein kinase B(AKT)] in epididymal adipose tissue were detected using real-time fluorescence quantitative PCR(RT-qPCR) and Western blotting. In vitro experiment: Using adriamycin(ADR) to induce 3T3-L1 aging adipocyte model, β-gal staining was used to observe cellular senescence, and miR-204 inhibitor and miR-204 mimic small interfering RNA were successfully constructed and transfected into 3T3-L1 adipocytes. Results:RT-qPCR and Western blot results showed that compared with the young group, the expression of AW112010 in the adipose tissue of aging mice was increased, while the expression of miR-204-5p was decreased. The expressions of POU2F2, p16, and p21 in the adipose tissue of aging mice were increased, while the expressions of INSR, IRS1, PI3K, GLUT4 mRNA and protein were decreased. The β-gal stainging results showed that the number of 3T3-L1 senescent adipocytes induced by ADR was significantly increased, and the expression levels of AW112010, POU2F2, p16, and p21 in ADR-induced senescent adipocytes were increased compared with the control group, while the expression levels of miR-204-5p, INSR, IRS1, PI3K, GLUT4 were decreased, and remaining glucose in the culture medium was increased. Compared with control, overexpression of miR-204 resulted in decreased expressions of aging indicators p16, p21, and target gene POU2F2 while the expressions of INSR and GLUT4 were increased.Conclusion:Upregulation of lncRNA AW112010 in adipocytes of aging mice may induce insulin resistance by targeting miR-204-5p/POU2F2/IRS1.