Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO2-induced cardiac injury using a mouse model. Methods Male C57BL/6 mice were intratracheally instilled with SiO2 to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed. Results SiO2 altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO2-induced mitochondrial damage and myocardial injury.SiO2 inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO. Conclusion Iron overload-induced ferroptosis contributes to SiO2-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO2 cardiotoxicity,potentially via modulation of the Nrf2 pathway.

Objective:To explore the effect and safety of endoscopic tubular musculoskeletal tumor surgery (ETMS) technology in spinal tumors.Methods:Clinical data were retrospectively collected from 18 spinal tumor patients who were treated with ETMS technology at Tianjin Medical University Cancer Institute and Hospital ( n=16) or the Affiliated Hospital of Qingdao University ( n=2) from November 2022 to December 2023. The total cohort included 11 males and 7 females, with the age at 60.3±8.6 years (range of 41-76). Two cases were diagnosed with benign tumors, four patients were diagnosed with spinal hematologic malignancies while other 12 cases were patients with spinal metastases. After localization under the C-arm X-ray machine, the spinal endoscopic channel is established using dilators. Soft tissue is dissected under endoscopic guidance to create an artificial cavity. Subsequently, the saline medium relied upon by the spinal endoscopic technique is removed, and posterior decompression and tumor curettage are performed using tubular techniques. Frankel grade classification and paraplegia index were used to evaluate the improvement of postoperative function and the VAS score was performed in pain scoring. The surgical complications and tumor evaluation were observed by postoperative outpatient and telephone follow-up. Results:The ETMS technology was successfully completed in all 18 patients with the mean operation time of 240.3±80.2 min. The median of intraoperative bleeding was 200.0(172.5, 350.0) ml and the mean postoperative drainage was 131.4±69.5 ml. The median value of postoperative hospitalization days was 6.0(4.0, 10.25) d. The paraplegia index decreased from 1.5(0, 3.0) preoperatively to 0(0, 1.25) postoperatively ( Z=-2.599, P=0.009). All the patients presented an improvement in Frankel grading after surgery except for one patient (downgrading from grade E to grade D). There was significantly difference in Frankel grading between preoperative and postoperative groups ( Z=2.812, P=0.005). The median value of preoperative VAS score was up to 5.5(4.0, 7.0) while the median value at postoperative, one month after surgery and three months after surgery were 1.5(1.0, 2.25), 1.0(0, 1.0) and 0(0, 1.0), respectively (χ 2=44.641, P<0.001). The 3-month postoperative VAS improvement rate was 91.2% (range 75%-100%). During a mean follow-up period of 7.6±6.2 months, none of the 18 patients presented surgical complications or tumor recurrence at surgical region. Only one patient died at 3.2 months after surgery until the last follow-up due to respiratory failure after lung tumor progression. The mean survival of the total cohort was up to 13.3 [95% CI (11.5, 15.0)] months. The 16 cases with spinal metastases or spinal hematological malignancies had a mean survival of 13.2 [95% CI (11.3, 15.0)] months. Conclusion:The ETMS technology presented good efficacy and safety in treatment of spinal tumors with low blood supply and with diameter less than 5cm.

Objective:To analyze the effectiveness and safety of the second course radiotherapy for unresectable colorectal cancer liver metastases.Methods:We retrospectively collected the data of 28 patients with unresectable colorectal cancer liver metastases who received the second course radiotherapy at Peking University Cancer Hospital and Institute from 2017 to 2023, to analyze the feasibility of re-irradiation.Results:For the 28 patients, the median follow-up time after re-irradiation was 20.2 months. The median time interval between the first- and second-course radiotherapy was 11.1 months. The median biologically effective doses of the first- and second-course radiotherapy were 100 Gy and 96 Gy, respectively. Stereotactic body radiotherapy was administered to 25 patients (89.3%) during the first course and 24 patients (85.7%) during the second course of radiotherapy. The mean equivalent dose in 2 Gy fractions to the normal liver was 10.1 Gy in the first-course radiotherapy and 7.9 Gy in the second-course radiotherapy. The complete response rate, partial response rate, and objective response rate after re-irradiation were 54.5%, 18.2%, and 72.7%, respectively. After re-irradiation, the 2-year cumulative local failure rate was 17.0% when calculated based on patients and 15.1% when calculated based on lesions, the 1-year progression-free survival rate was 27.4%, and the 3-year overall survival rate was 46.7%. The second-course radiotherapy was well tolerated, with most patients (75.0%) experiencing grade 1-2 acute adverse reactions and only one case (3.6%) experiencing grade 3 acute adverse events.Conclusions:Second course radiotherapy is an effective and safe treatment approach for selected patients with unresectable colorectal cancer liver metastases.

Objective:To investigate the relationship between long non-coding RNA (lncRNA) DHRS4-AS1 and disease-free survival in osteosarcoma patients and the mechanisms of its effect on proliferation and migration of osteosarcoma cells in vitro.Methods:The data of DHRS4-AS1 transcriptome levels and survival status of osteosarcoma patients in GEPIA database were collected since the database was established, and the patients were divided into high DHRS4-AS1 expression group and low DHRS4-AS1 expression group based on the median DHRS4-AS1 transcriptome level, with 59 cases in each group, and the Kaplan-Meier method was used to analyze the disease-free survival of the two groups. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of DHRS4-AS1 in osteosarcoma cell lines MG-63, HOS, 143B, U-2OS, Saos2 and normal osteoblast cell line hFOB1.19, and the osteosarcoma cell line with the lowest DHRS4-AS1 expression level was selected for subsequent experiments. The plasmid carrying DHRS4-AS1 sequence and the plasmid carrying negative control sequence were transfected into the selected osteosarcoma cells as DHRS4-AS1 group and control group. CCK-8 method was used to detect the proliferation of each group of cells, and the absorbance value was used as the cell proliferation ability; cell scratch assay was used to detect the migration of each group of cells. The bioinformatics website starBase V2.0 was used to predict the target genes of DHRS4-AS1, and the dual luciferase reporter gene assay was used to verify the targeting relationship between DHRS4-AS1 and the target genes. The expression levels of target genes and downstream genes of osteosarcoma cells in control group and DHRS4-AS1 group were detected by qRT-PCR and Western blotting.Results:Survival analysis showed that the disease-free survival of osteosarcoma patients in the high DHRS4-AS1 expression group in GEPIA database was superior to that of the low DHRS4-AS1 expression group ( P < 0.001). Compared with normal osteoblastic hFOB1.19 cells, the expression level of DHRS4-AS1 was low in all osteosarcoma cells (all P < 0.01), with the lowest expression level of DHRS4-AS1 in U-2OS cells ( P < 0.001). Cell proliferation ability was reduced in U-2OS cells of the DHRS4-AS1 group after 1, 2, 3 and 4 d of culture compared with the control group (all P < 0.05). The migration rate of U-2OS cells in the DHRS4-AS1 group was lower than that in the control group [(31±6)% vs. (63±4)%, t = 4.38, P = 0.005]. starBase V2.0 website predicted that DHRS4-AS1 complementarily bound to miRNA-411-3p (miR-411-3p); dual luciferase reporter gene assay showed that miR-411-3p overexpression reduced the luciferase activity of the wild-type DHRS4-AS1 reporter gene ( P < 0.001), but had no effect on the luciferase activity of the mutant DHRS4-AS1 reporter gene ( P > 0.05). qRT-PCR showed that the relative expression of miR-411-3p in U-2OS cells of the DHRS4-AS1 group was low (0.22±0.06 vs. 1.06±0.23, t = 3.55, P = 0.012) and the relative expression of metastasis suppressor MTSS1 mRNA was high (5.58±1.03 vs. 1.06±0.22, t = 4.28, P = 0.005) compared with the control group; Western blotting showed that MTSS1 expression was elevated, and the expression levels of cell proliferation phenotype proteins CDK3 and cyclin C and cell migration phenotype proteins ZEB2 and KLF8 were low. Conclusions:Osteosarcoma patients with high expression of lncRNA DHRS4-AS1 have better disease-free survival, and its expression is low in osteosarcoma cell lines. DHRS4-AS1 may promote MTSS1 gene expression and inhibit cell proliferation and migration by targeting and down-regulating miR-411-3p expression in osteosarcoma cells.

ObjectiveTo observe the regulatory effect of Yuyetang on Ghrelin level in rats with type 2 diabetes mellitus （T2DM）-induced cognitive impairment （DCI） and explore the pathway in the prevention and treatment of DCI. MethodThe T2DM model was induced in rats by intraperitoneal injection of streptozotocin （STZ） combined with the high-fat and high-sugar diet （STZ）. The model rats were divided into model group， metformin group （200 mg·kg^-1）， and low-，medium-， and high-dose Yuyetang groups（4.575，9.15， 18.3 g·kg^-1）according to the blood glucose， with 10 rats in each group. A normal group was also set up. The rats were administered with corresponding drugs by gavage for 30 days， and the body weight and blood glucose of the rats in each group were observed and recorded. After drug intervention， the learning and memory abilities of rats were tested by the Morris water maze. After the test， the whole brains of rats were sampled for hematoxylin-eosin （HE） staining to observe the pathological changes in the hippocampal CA1 region， and the expression of Ghrelin in gastric tissues and hippocampal CA1 region was detected by immunohistochemistry. ResultCompared with the normal group ， the model group showed increased blood glucose（P<0.01），reduced body weight（P<0.01），prolonged escape latency（P<0.05，P<0.01）， shortened retention time and movement distance in the target area，decreased number of platform crossings（P<0.01）， abnormal morphology and structure of cells with disordered arrangement and reduced number in the hippocampal CA1 region， and decreased expression of Ghrelin in the serum，hippocampal CA1 region， and gastric tissues（P<0.05， P<0.01）. Compared with the model group， the medium- and high-dose Yuyetang groups showed increased body weight， while all Yuyetang groups showed reduced blood glucose（P<0.01）， shortened escape latency （P<0.05）， prolonged retention time and movement distance in the target area，increased platform crossings （P<0.05， P<0.01）， improved morphology and structure of cells， increased number of normal cell in the hippocampal CA1 region， and elevated Ghrelin levels in the serum， gastric tissues， and hippocampal CA1 region（P<0.05， P<0.01）. ConclusionYuyetang can effectively improve the cognitive ability of DCI rats， and its mechanism may be related to the regulation of Ghrelin levels in the serum， hippocampal CA1 region， and gastric tissues.

Objective:To translate the Cardiac Symptom Survey and analyze its reliability and validity in the post-valvular heart replacement survey and to provide the basis for the clinical application of this scale.Methods:The symptoms of 233 patients after heart valve replacement were investigated in Suining Central Hospital by Chinese version of the Cardiac Symptom Survey. The reliability of the scale was evaluated by Cronbach'α coefficient and the split half coefficient, the validity of the scale was evaluated by exploratory factor analysis and content validity index.Results:The internal consistency coefficient of the Chinese version of the Cardiac Symptom Survey ranged from 0.875 to 0.968, both above 0.870.The split half coefficient was 0.699,which demonstrated better internal consistency.The content validity index of the Chinese version of the Cardiac Symptom Survey ranged from 0.84 to 1.00.Factor analysis got five factors, which explained 68.133% of the total variance.Conclusions:The Chinese version of the Cardiac Symptom Survey has good reliability and validity in the investigation of the symptoms of patients after heart valve replacement, and can be used for the investigation and management of the symptoms of patients after heart valve replacement.

Background: Arctic-like (AL) lineages of rabies viruses (RABVs) remains endemic in some Arctic and Asia countries. However, their evolutionary dynamics are largely unappreciated. Objectives: We attempted to estimate the evolutionary history, geographic origin and spread of the Arctic-related RABVs. Methods: Full length or partial sequences of the N and G genes were used to infer the evolutionary aspects of AL RABVs by Bayesian evolutionary analysis. Results: The most recent common ancestor (tMRCA) of the current Arctic and AL RABVs emerged in the 1830s and evolved independently after diversification. Population demographic analysis indicated that the viruses experienced gradual growth followed by a sudden decrease in its population size from the mid-1980s to approximately 2000.Genetic flow patterns among the regions reveal a high geographic correlation in AL RABVs transmission. Discrete phylogeography suggests that the geographic origin of the AL RABVs was in east Russia in approximately the 1830s. The ancestral AL RABV then diversified and immigrated to the countries in Northeast Asia, while the viruses in South Asia were dispersed to the neighboring regions from India. The N and G genes of RABVs in both clades sustained high levels of purifying selection, and the positive selection sites were mainly found on the C-terminus of the G gene. Conclusions The current AL RABVs circulating in South and North Asia evolved and dispersed independently.

Objective:To evaluate the pedicled bridge transplantation with medial leg skin flap and medial hemi-soleus muscle flap for the treatment of soft tissue defects at the contrallateral leg.Methods:Between January of 2012 and January of 2016, 8 patients with soft tissue defects at the leg were treated at Department of Orthopedic Surgery, Hand and Foot Surgery Hospital of Lanzhou. They were 5 men and 3 women, aged from 19 to 50 years (mean, 35 years). All of them were treated by bridge transplantation with medial leg skin flap and medial hemi-soleus muscle flap pedicled with posterior tibial artery. The size of the defects ranged from 10 cm×9 cm to 13 cm×8 cm. The immediate coverage of the muscle flaps and vessel pedicle was repaired by a meshed split-thickness skin graft. The donor site was closed directly. The therapeutic efficacy was assessed at the final follow-up according to the criteria by Iowa for tibial fractures.Results:All the skin flaps and muscle flaps survived without any vascular crisis. One case developed necrosis of small skin graft at the distal muscle flap which spontaneously healed after dressing change for 2 weeks. Their follow-up ranged from 2.5 to 4.5 years (mean, 3.8 years). A good contour was confirmed at the recipient area. By the Iowa criteria at the final follow-up, 3 cases were excellent, 4 good and one fair.Conclusion:Pedicled bridge transplantation with medial leg skin flap and medial hemi-soleus muscle flap is a good treatment for soft tissue defects at the contrallateral leg which has only one major blood vessel, reducing damage to the donor site.

Objective:To explore the safety and efficacy of watch and wait strategy and organ preservation surgery after total neoadjuvant treatment for MRI stratified low-risk rectal cancer.Methods:A prospective single arm phase Ⅱ trial developed at Department of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute was preliminarily analyzed. Subjects were enrolled from August 2016 to January 2019. Low-risk rectal cancer with following MRI features were recruited: mid-low tumor, mrT2-3b, MRF (-), EMVI (-), CRM (-), differentiation grade 1-3. Patients received intensity-modulated radiotherapy (IMRT) 50.6 Gy/22f with concurrent capecitabine and 4 cycles of consolidation CAPEOX. Patients with cCR/near-cCR confirmed by physical examination, rectal MRI, endoscopy, and serum CEA were recommended for watch & wait approach or local excision (LE). The main study outcomes were 2-year organ preservation rate (OPR) and sphincter preservation rate (SPR).Results:Thirty-eight patients were eligible for analysis, including 24 males and 14 females with median age of 56 years; 9 cases of mrT2 (23.7%), 14 cases of mrT3a (36.8%) and 15 cases of mrT3b (39.5%); 5 cases of well differentiated adenocarcinoma (13.2%), 32 cases of moderately differentiated adenocarcinoma (84.2%) and 1 case of mucinous adenocarcinoma (2.6%). Carcinoemobryonic antigen (CEA) was elevated before treatment in 1 case. One case (2.6%) of grade 3 radiation dermatitis occurred during IMRT; 18 cases (47.4%) occurred grade 3 to 4 adverse events during consolidation chemotherapy. After total neoadjuvant treatment, the cCR and near-cCR rates were 42.1% (16/38) and 23.7% (9/38), respectively, while non-cCR rate was 34.2% (13/38). Twenty patients (20/38, 52.6%) of cCR or near-cCR underwent watch & wait approach, with a local regrowth rate of 20% (4/20). Four patients received LE, including one salvage LE. Thirteen patients (4 were ypCR) received radical resection, including 10 cases of initial low anterior resections (LAR), 1 cases of initial abdominal perineal resection (APR) and 2 cases of salvage LAR, four patients refused operation. The median follow-up time was 23.5 (8.5-38.3) months. At the last interview of follow-up, the OPR and SPR were 52.6% (20/38) and 84.2% (32/38), respectively. Only one patient developed lung metastasis and no local recurrence occurred after radical resection or LE.Conclusion:Total neoadjuvant treatment for low-risk rectal cancer achieves high cCR/near-cCR rate, with increased probability of receiving watch and wait approach and organ preservation in this subgroup.

Objective:To explore the safety and efficacy of watch and wait strategy and organ preservation surgery after total neoadjuvant treatment for MRI stratified low-risk rectal cancer.Methods:A prospective single arm phase Ⅱ trial developed at Department of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute was preliminarily analyzed. Subjects were enrolled from August 2016 to January 2019. Low-risk rectal cancer with following MRI features were recruited: mid-low tumor, mrT2-3b, MRF (-), EMVI (-), CRM (-), differentiation grade 1-3. Patients received intensity-modulated radiotherapy (IMRT) 50.6 Gy/22f with concurrent capecitabine and 4 cycles of consolidation CAPEOX. Patients with cCR/near-cCR confirmed by physical examination, rectal MRI, endoscopy, and serum CEA were recommended for watch & wait approach or local excision (LE). The main study outcomes were 2-year organ preservation rate (OPR) and sphincter preservation rate (SPR).Results:Thirty-eight patients were eligible for analysis, including 24 males and 14 females with median age of 56 years; 9 cases of mrT2 (23.7%), 14 cases of mrT3a (36.8%) and 15 cases of mrT3b (39.5%); 5 cases of well differentiated adenocarcinoma (13.2%), 32 cases of moderately differentiated adenocarcinoma (84.2%) and 1 case of mucinous adenocarcinoma (2.6%). Carcinoemobryonic antigen (CEA) was elevated before treatment in 1 case. One case (2.6%) of grade 3 radiation dermatitis occurred during IMRT; 18 cases (47.4%) occurred grade 3 to 4 adverse events during consolidation chemotherapy. After total neoadjuvant treatment, the cCR and near-cCR rates were 42.1% (16/38) and 23.7% (9/38), respectively, while non-cCR rate was 34.2% (13/38). Twenty patients (20/38, 52.6%) of cCR or near-cCR underwent watch & wait approach, with a local regrowth rate of 20% (4/20). Four patients received LE, including one salvage LE. Thirteen patients (4 were ypCR) received radical resection, including 10 cases of initial low anterior resections (LAR), 1 cases of initial abdominal perineal resection (APR) and 2 cases of salvage LAR, four patients refused operation. The median follow-up time was 23.5 (8.5-38.3) months. At the last interview of follow-up, the OPR and SPR were 52.6% (20/38) and 84.2% (32/38), respectively. Only one patient developed lung metastasis and no local recurrence occurred after radical resection or LE.Conclusion:Total neoadjuvant treatment for low-risk rectal cancer achieves high cCR/near-cCR rate, with increased probability of receiving watch and wait approach and organ preservation in this subgroup.