Objective To analyze and verify the role of senescent genes in the treatment,prognosis,and tumor microenvironment(TME)characteristics of osteoblastic osteosarcoma,bioinformatic methods were employed.Methods Senescent genes were obtained from the China National Genome Science database(https://ngdc.cncb.ac.cn/aging/index).The gene expression profile and clinical information of osteosarcoma patients were sourced from the TARGET database(https://ocg.cancer.gov/programs/target),while single-cell RNA-sequencing(scRNA-seq)data was collected from GSE162454 on the Gene Expression Omnibus(GEO)for downstream analysis.Osteosarcoma cells were classified based on scRNA-seq,and differential expression analysis between osteoblasts/chondroblasts and other cell types was conducted to identify differently expressed genes(DEGs).After matching with the senescent genes,prognostic senescent DEGs were identified through univariable and multivariable Cox regression analysis.Subsequently,the osteosarcoma senescent-related model(OSRM)was constructed,and the risk score was calculated.The role of OSRM in treatment,prognosis,and TME of osteosarcoma was further investigated.Results The analysis revealed that GSE162454 contained 6 osteosarcoma samples,with 19933 cells identified after filtering,quality control,and normalization.Seventeen cellular subtypes were identified using uniform manifold approximation and projection(UMAP)methods.A total of 4821 DEGs were found between osteoblasts/chondroblasts and other subtypes,with 132 senescent DEGs obtained after matching with the senescent gene set.In the TARGET database,4 prognostic senescent DEGs[ADH5(alcohol dehydrogenase 5),ARHGAP1(Rho GTPase activating protein 1),APOE(apolipoprotein E),and ATF4(activating transcription factor 4)]were identified through univariable and multivariable Cox analyses to construct OSRM.Based on risk score,patients were stratified into high-and low-risk groups,with the latter showing better prognosis(HR=0.13,95%CI 0.06-0.28,P<0.001)and higher sensitivity to immune checkpoint inhibitors.qRT-PCR and Western blotting confirmed the high expression of senescent genes ADH5(P<0.01),APOE(P<0.01),and ATF4(P<0.05)in the K7M2 osteosarcoma cell line,suggesting the potential for predicting the response to anti-PD-1 immunotherapy for osteosarcoma.Conclusions scRNA-seq facilitated the division of osteosarcoma into 17 cell subtypes.ADH5,ARHGAP1,APOE,and ATF4 emerged as potential cancer-promoting or suppressing senescent genes in osteosarcoma.OSRM was found to be associated with treatment response,prognosis,and TME characteristics,thereby promoting the molecular pathological diagnosis of osteoblastic osteosarcoma and prediction for anti-PD-1 immunotherapy.

Objective: To investigate the efficacy of humanized anti-CD25 monoclonal antibody for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods: A total of 64 patients with SR-aGVHD between June 2019 and October 2020 in Suchow Hopes Hematology Hospital were enrolled in this study. Humanized anti-CD25 monoclonal antibodies 1 mg·kg(-1)·d(-1) were administered on days 1, 3, and 8, and then once per week according to the disease progression. Efficacy was assessed at days 7, 14, and 28 after humanized anti-CD 25 treatment. Results: Of the 64 patients with a median age of 31 (15-63) years, 38 (59.4%) were male and 26 (40.6%) were female. The overall response (OR) rate of the humanized CD25 monoclonal antibody in 64 patients with SR-aGVHD on days 7, 14, and 28 were 48.4% (31/64), 53.1% (34/64), and 79.7% (51/64), respectively. Liver involvement is an independent risk factor for poor efficacy of humanized CD25 monoclonal antibody for SR-aGVHD at day 28 (OR=9.588, 95% CI 0.004-0.291, P=0.002). The median follow-up time for all patients was 17.1 (0.2-50.8) months from the start of humanized CD25 monoclonal antibody therapy. The 1- and 2-year OS rates were 63.2% (95% CI 57.1% -69.3%) and 52.6% (95% CI 46.1% -59.1%), respectively. The 1- and 2-year DFS rates were 58.4% (95% CI 52.1% -64.7%) and 49.8% (95% CI 43.4% -56.2%), respectively. The 1- and 2-year NRM rates were 28.8% (95% CI 23.1% -34.5%) and 32.9% (95% CI 26.8% -39.0%), respectively. The results of the multifactorial analysis showed that liver involvement (OR=0.308, 95% CI 0.108-0.876, P=0.027) and GVHD grade Ⅲ/Ⅳ (OR=9.438, 95% CI 1.211-73.577, P=0.032) were independent risk factors for OS. Conclusion: Humanized CD25 monoclonal antibody has good efficacy and safety for SR-aGVHD. This study shows that SR-aGVHD with pretreatment grade Ⅲ/Ⅳ GVHD and GVHD involving the liver has poor efficacy and prognosis and requires early intervention.
Adult ; Female ; Humans ; Male ; Middle Aged ; Acute Disease ; Antibodies, Monoclonal/therapeutic use* ; Graft vs Host Disease/therapy* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Retrospective Studies ; Salvage Therapy/methods* ; Steroids ; Adolescent ; Young Adult

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

Objective: To evaluate the efficiency of internal carotid artery (ICA) embolization technology in endoscopic salvage surgery for recurrent nasopharyngeal carcinoma (rNPC) invading the ICA. Methods: From January 2016 to March 2021, 83 patients with rNPC who invaded the ICA and underwent endoscopic extended nasopharyngectomy were retrospectively collected from the Eye & ENT Hospital in Fudan University, including 60 males and 23 females. The age of the patients ranged from 27 to 77 years. The standard of ICA invasion was that the distance from the lesion to the ICA on enhanced MRI was ≤ 1.8 mm. The clinical characteristics, ICA management strategy and survival prognosis of patients were analyzed, and the effectiveness of ICA embolization was evaluated. Kaplan-Meier method was used to calculate the survival rate and Log-rank test was used to compare the difference. Results: In 83 patients with rNPC, there were 13 patients with rT2, 38 patients with rT3, 32 patients with rT4, and 16 patients had lymph node metastasis. A total of 37 patients (44.6%) underwent ICA coil embolization before surgery, of which 2 cases underwent external carotid-middle cerebral artery artery bypass grafting and ICA embolization due to positive balloon occlusion test (BOT). Patients with positive surgical margin accounted for 24.1% (20/83). Among them, patients with rT4 and patients without ICA embolization had a higher positive rate of surgical margin (P value was 0.001, 0.043, respectively). The 3-year overall survival (OS) and progression free survival (PFS) rate of all patients was 46.5% and 26.7%, respectively. In addition, the 3-year OS and PFS of patients with ICA embolization was significantly higher than those without ICA embolization, respectively (69.1% vs 27.8%, P=0.003; 33.9% vs 18.9%, P=0.018). Only 2 patients (2/37, 5.4%) had cerebral infarction complications after coil embolization of the affected ICA due to negative BOT. Conclusion: Preoperative ICA embolization can be used to treat patients with rNPC invading the ICA, improve the total removal rate and survival rate of patients, which is an effective salvage treatment.
Humans ; Male ; Female ; Adult ; Middle Aged ; Aged ; Nasopharyngeal Carcinoma ; Salvage Therapy ; Retrospective Studies ; Carotid Artery, Internal ; Neoplasm Recurrence, Local/surgery* ; Nasopharyngeal Neoplasms/pathology*

Objective: To evaluate the feasibility of the endoscopic transnasal approach (ETA) and to analyze the outcomes and factors of this surgical technique in the management of the tumor invading the anterior skull base. Methods: A retrospective analysis was performed on 42 patients (31 males and 11 females, with mean age of 49 years) with sinonasal tumor invading the anterior skull base, who underwent ETA from June 2015 to April 2019 in Eye, Ear, Nose and Throat Hospital of Fudan University. Pathologically, there were 15 cases of squamous carcinoma (14 patients with T4bN0M0 and 1 patient with T4bN1M0) and 27 of olfactory neuroblastomas with Kadish stage C. Anterior skull base reconstruction was performed using the vascular pedicled nasoseptal mucoperiosteal flap and fascia lata. Brain non-contrast-enhanced CT was performed on the first postoperative day to exclude massive pneumocephalus, relevant brain edema and subarachnoid hemorrhage. Sinonasal contrast-enhanced MR was performed to assess the extent of the tumor removal. Kaplan-Meier analysis was used to calculate the overall survival (OS) and Cox multivariate regression analysis was used to determine the prognostic factors. Results: The mean duration of the surgery was 452 minutes. Total resection was performed in 36 patients (85.7%), subtotal resection in 2 patients (4.8%) with orbital involvement, partial resection in one patient (2.4%) with injury of the internal carotid artery. One patient (2.4%) underwent the second resection because of the tumor residual, two patients (4.8%) with unsure tumor residual. Mean follow-up was 20 months, with 17 months of median follow-up. One-, two-and three-year overall survival was 86.5%, 76.9% and 64.5%, respectively. For squamous carcinoma, one-, two-and three-year overall survival was 86.2%, 86.2% and 57.4%, respectively. For olfactory neuroblastomas, One-, two-and three-year overall survival was 86.9%, 75.3% and 67.8%, respectively. Multivariate analysis showed that tumor residual (P=0.001) and recurrence (P<0.01) were independent prognostic factors for survival. Conclusions: The ETA is safe and feasible in selected patients with sinonasal tumor invading the anterior skull base. Tumor residual and recurrence are independent prognostic factors for survival.
Female ; Humans ; Male ; Middle Aged ; Nasal Cavity ; Neoplasm Recurrence, Local ; Nose Neoplasms/surgery* ; Retrospective Studies ; Skull Base/surgery* ; Skull Base Neoplasms/surgery*

Objective:To examine the early outcome of valve sparing aortic root replacement with reimplantation technique (David procedure) with partial upper sternotomy.Methods:From April 2016 to April 2020, 31 patients underwent valve sparing aortic root replacement under partial upper sternotomy at Vascular Surgery Center, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. There were 28 males and 3 females, aging (44±13) years (range: 11 to 65 years). Preoperative aortic regurgitation was found greater than moderate in 15 patients, moderate in 6 patients and less than moderate in 10 patients. The diameter of aortic annulus was (26±3) mm (range: 21 to 34 mm), the diameter of aortic sinus was (51±6) mm (range: 41 to 68 mm), the diameter of ascending aorta was (43±8) mm (range: 26 to 62 mm). The preoperative ejection fraction was (65±4) % (range: 59% to 72%) and left ventricular end-diastolic diameter was (55±6) mm (range: 42 to 68 mm). All cases were treated with David Ⅰ procedure, including simple David procedure in 26 patients, David+ascending aorta and partial aortic arch replacement in 3 patients, David+thoracic endovascular aortic repair in 1 patient, David+stent elephant trunk implantation in 1 patient.Results:The operation time, cardiopulmonary bypass time and aortic cross-clamping time were (330±58) minutes (range: 214 to 481 minutes), (138±23) minutes (range: 106 to 192 minutes) and (108±17) minutes (range: 82 to 154 minutes), respectively. There were no death and serious complications (stroke, myocardial infarction, renal insufficiency, severe infection, etc.). The postoperative drainage volume within 24 hours was (314±145) ml (range: 130 to 830 ml). The intubation time was (14±3) hours (range: 8 to 21 hours), and the ICU time was ( M( Q R)) 2.1(1.5) days (range: 1.0 to 5.0 days). Eight patients had no blood transfusion, the proportion of red blood cell use was 9.7% (3/31), plasma use was 22.6% (7/31), and platelet use was 71.0% (22/31). The postoperative left ventricular ejection fraction was (62±4)% (range: 54% to 69%), and left ventricular end-diastolic diameter was (48±4) mm (range: 39 to 56 mm). After operation, aortic regurgitation was significantly improved, with no more than moderate regurgitation, small to moderate regurgitation in 3 patients, minor regurgitation in 3 patients, micro regurgitation in 12 patients and no regurgitation in 13 patients. The follow-up period was 3.5(6.1) months (range: 2.0 to 39.0 months). Echocardiographic follow-up data were obtained in 26 cases, including moderate regurgitation in 1 patient, small to moderate regurgitation in 9 patients, minor regurgitation in 5 patients, micro regurgitation in 6 patients and no regurgitation in 5 patients. There were no major adverse cardiovascular events and aortic events during the follow-up period. No patient was reoperated for aortic regurgitation. Conclusion:Valve sparing aortic root replacement under partial upper sternotomy is safe and feasible, and the early result is satisfactory.

Objective:To examine the early outcome of valve sparing aortic root replacement with reimplantation technique (David procedure) with partial upper sternotomy.Methods:From April 2016 to April 2020, 31 patients underwent valve sparing aortic root replacement under partial upper sternotomy at Vascular Surgery Center, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. There were 28 males and 3 females, aging (44±13) years (range: 11 to 65 years). Preoperative aortic regurgitation was found greater than moderate in 15 patients, moderate in 6 patients and less than moderate in 10 patients. The diameter of aortic annulus was (26±3) mm (range: 21 to 34 mm), the diameter of aortic sinus was (51±6) mm (range: 41 to 68 mm), the diameter of ascending aorta was (43±8) mm (range: 26 to 62 mm). The preoperative ejection fraction was (65±4) % (range: 59% to 72%) and left ventricular end-diastolic diameter was (55±6) mm (range: 42 to 68 mm). All cases were treated with David Ⅰ procedure, including simple David procedure in 26 patients, David+ascending aorta and partial aortic arch replacement in 3 patients, David+thoracic endovascular aortic repair in 1 patient, David+stent elephant trunk implantation in 1 patient.Results:The operation time, cardiopulmonary bypass time and aortic cross-clamping time were (330±58) minutes (range: 214 to 481 minutes), (138±23) minutes (range: 106 to 192 minutes) and (108±17) minutes (range: 82 to 154 minutes), respectively. There were no death and serious complications (stroke, myocardial infarction, renal insufficiency, severe infection, etc.). The postoperative drainage volume within 24 hours was (314±145) ml (range: 130 to 830 ml). The intubation time was (14±3) hours (range: 8 to 21 hours), and the ICU time was ( M( Q R)) 2.1(1.5) days (range: 1.0 to 5.0 days). Eight patients had no blood transfusion, the proportion of red blood cell use was 9.7% (3/31), plasma use was 22.6% (7/31), and platelet use was 71.0% (22/31). The postoperative left ventricular ejection fraction was (62±4)% (range: 54% to 69%), and left ventricular end-diastolic diameter was (48±4) mm (range: 39 to 56 mm). After operation, aortic regurgitation was significantly improved, with no more than moderate regurgitation, small to moderate regurgitation in 3 patients, minor regurgitation in 3 patients, micro regurgitation in 12 patients and no regurgitation in 13 patients. The follow-up period was 3.5(6.1) months (range: 2.0 to 39.0 months). Echocardiographic follow-up data were obtained in 26 cases, including moderate regurgitation in 1 patient, small to moderate regurgitation in 9 patients, minor regurgitation in 5 patients, micro regurgitation in 6 patients and no regurgitation in 5 patients. There were no major adverse cardiovascular events and aortic events during the follow-up period. No patient was reoperated for aortic regurgitation. Conclusion:Valve sparing aortic root replacement under partial upper sternotomy is safe and feasible, and the early result is satisfactory.

Air Pollution ; China ; Humans ; Meteorological Concepts ; Outpatients ; Particulate Matter/analysis* ; Skin Diseases/epidemiology*

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Objective    To discuss the efficacy of type Ⅱ hybrid aortic arch repair for type A aortic dissection in patients of different age groups. Methods    We retrospectively analyzed the clinical data of 126 patients with type A aortic dissection admitted to the Fuwai Hospital between January 2016 and December 2018, including 78 (61.9%) males and 48 (38.1%) females, with an average age of 61.8±6.9 years. The patients were divided into an elderly group (≥60 years, n=82) and a non-elderly group (<60 years, n=44). The preoperative, intraoperative and postoperative data of patients in the two groups were compared. Results    The age between the elderly and non-elderly group was significantly different (65.9±4.1 years vs. 54.3±4.1 years, P<0.010), and no significant difference was found between the two groups in other preoperative baseline data. There were 6 (4.8%) patients of early death, 3 (2.4%) patients of stroke and 2 (1.6%) patients of paralysis. A total of 194 stents were implanted, and the average dimeter of the stents was 33.6±1.8 mm and the average length was 199.0±6.7 mm. The non-elderly group had shorter mechanical ventilation time (31.9±41.7 h vs. 61.0±89.2 h, P=0.043) and ICU stay time (77.8±51.4 h vs. 143.1±114.4 h, P<0.001) than the elderly group. There was no significant difference in in-hospital mortality rate, reoperation rate or survival rate between the two groups (P>0.05). Follow-up time was 1-43 (22.6±10.8) months, and 3 patients were lost. There were 104 (82.5%) patients of complete thrombus formation of false lumen in stent and endoleak was reported in 11 (9.2%) patients. Conclusion    Type Ⅱ hybrid aortic arch repair offers an alternative approach to acute type A aortic dissection with acceptable early and mid-term clinical effects. The non-elderly patients have a similar early treatment effect to the elderly patients, but have a better mid-term outcome.