In non-small cell lung cancer(NSCLC),the heterogeneity promotes drug resistance,and the restricted expression of programmed death-ligand 1(PD-L1)limits the immunotherapy benefits.Based on the mechanisms related to translation regulation and the association with PD-L1 of methyltransferase-like 3(METTL3),the novel small-molecule inhibitor STM2457 is assumed to be useful for the treat-ment of NSCLC.We evaluated the efficacy of STM2457 in vivo and in vitro and confirmed the effects of its inhibition on disease progression.Next,we explored the effect of STM2457 on METTL3 and revealed its effects on the inhibition of catalytic activity and upregulation of METTL3 protein expression.Importantly,we described the genome-wide characteristics of multiple omics data ac-quired from RNA sequencing,ribosome profiling,and methylated RNA immunoprecipitation sequencing data under STM2457 treatment or METTL3 knockout.We also constructed a model for the regulation of the translation of METTL3 and PD-L1.Finally,we found PD-Ll upregulation by STM2457 in vivo and in vitro.In conclusion,STM2457 is a potential novel suppressor based on its inhibitory effect on tumor progression and may be able to overcome the heterogeneity based on its impact on the translatome.Furthermore,it can improve the immunotherapy outcomes based on PD-L1 upregulation in NSCLC.

Clinical data from 11 previously diagnosed and treated patients with hyperthyroidism(Graves′ disease) complicated by liver failure were collected. Among them, 4 cases were drug-induced liver injury leading to liver failure, 1 case had a history of schistosomal liver cirrhosis combined with hyperthyroidism, and 6 cases had hyperthyroidism-induced liver injury(HILI) leading to liver failure. During hospitalization, all patients received supportive therapy and symptomatic treatment with β-blockers. Nine patients were treated with glucocorticoids and artificial liver support therapy. Among the 11 patients, 2 died, 8 patients achieved normal thyroid and liver function within 1-12 months after treatment, and 1 patient with liver cirrhosis had stable liver function in the later stage. After improvement in liver function, 7 patients received isotope therapy, 1 patient underwent total thyroidectomy, and 1 patient received medication. These results indicate that the clinical characteristics differ for drug-induced liver injury and HILI-related liver failure. Early initiation of artificial liver support therapy, in addition to β-blockers and glucocorticoids, is important in alleviating thyroid toxicity and liver damage, thus creating an opportunity for subsequent radioactive iodine or surgical treatment.

Objective:To investigate the clinical effect of the relaying perforator flap for repairing the donor site of the anterolateral thigh flap.Methods:From March 2019 to June 2020, 28 consecutive patients who underwent anterolateral thigh free flap reconstruction for limb soft tissue defects were retrospectively reviewed. A relaying perforator flap was selected from one of the four areas adjacent to the donor site of the anterolateral thigh flap for covering the donor site of the anterolateral thigh flap. The secondary donor site was closed directly. The followed-up contents included the appearance and texture of the flaps. The postoperative followed-up was performed through outpatient visits, telephone, and WeChat interviews.Results:A total of 28 patients were included, with an average age of 37.3 (ranging from 15 to 65). The relaying perforator flap was selected from the anteromedial thigh region ( n=13), the proximal anterolateral thigh region( n=6), the distal anterolateral thigh region ( n=5), and the ilioinguinal region ( n=4). The size of the anterolateral thigh flap ranged from 12.0 cm×10.0 cm to 20.0 cm×13.0 cm, and the size of the relaying perforator flap ranged from 6.0 cm×5.0 cm to 11.0 cm×7.5 cm. The followed-up time ranged from 1 to 6 months (mean 4.8 months). The color, texture, and contour of the flaps were good. Only one linear scar is left in the donor site. Two cases with small necrosis (1.0 cm×2.0 cm and 1.5 cm×1.5 cm, respectively) were found in the distal edge of relaying perforator flaps. Conclusions:The relaying perforator flap is considered as an optimized and reliable method for repairing the donor site of an anterolateral thigh flap and should be recommended.

Objective:To investigate the clinical effect of the relaying perforator flap for repairing the donor site of the anterolateral thigh flap.Methods:From March 2019 to June 2020, 28 consecutive patients who underwent anterolateral thigh free flap reconstruction for limb soft tissue defects were retrospectively reviewed. A relaying perforator flap was selected from one of the four areas adjacent to the donor site of the anterolateral thigh flap for covering the donor site of the anterolateral thigh flap. The secondary donor site was closed directly. The followed-up contents included the appearance and texture of the flaps. The postoperative followed-up was performed through outpatient visits, telephone, and WeChat interviews.Results:A total of 28 patients were included, with an average age of 37.3 (ranging from 15 to 65). The relaying perforator flap was selected from the anteromedial thigh region ( n=13), the proximal anterolateral thigh region( n=6), the distal anterolateral thigh region ( n=5), and the ilioinguinal region ( n=4). The size of the anterolateral thigh flap ranged from 12.0 cm×10.0 cm to 20.0 cm×13.0 cm, and the size of the relaying perforator flap ranged from 6.0 cm×5.0 cm to 11.0 cm×7.5 cm. The followed-up time ranged from 1 to 6 months (mean 4.8 months). The color, texture, and contour of the flaps were good. Only one linear scar is left in the donor site. Two cases with small necrosis (1.0 cm×2.0 cm and 1.5 cm×1.5 cm, respectively) were found in the distal edge of relaying perforator flaps. Conclusions:The relaying perforator flap is considered as an optimized and reliable method for repairing the donor site of an anterolateral thigh flap and should be recommended.

Objective To investigate the postoperative complications of ex vivo liver resection combined with autologous liver transplantation in the treatment of end-stage hepatic alveolar echinococcosis at high altitude and related prevention and treatment strategies. Methods Surgical data and follow-up data were collected from 11 patients with end-stage hepatic alveolar echinococcosis who underwent autologous liver transplantation in Qinghai People's Hospital from January 2013 to March 2019, and intraoperative and postoperative conditions were analyzed. Results All 11 patients underwent autologous liver transplantation successfully, without intraoperative death, among whom 2(18.18%) underwent hemi-extracorporeal hepatectomy and 9 (81.82%) underwent total extracorporeal hepatectomy. For the reconstruction of the retrohepatic inferior vena cava, 2 patients (18.18%) underwent reconstruction with the autologous great saphenous vein, 4 patients (36.36%) underwent reconstruction with artificial vessels, and the autologous retrohepatic inferior vena cava was preserved in 5 patients (45.45%). For biliary reconstruction, 8 patients (72.73%) underwent choledochoenterostomy and 3 (27.27%) underwent choledochocholedochostomy. The main postoperative complications of the 11 patients included bleeding in 2 patients (18.18%), bile leakage and abdominal infection in 4 patients (36.36%), bilioenteric anastomotic stenosis in 1 patient (9.09%), thrombus in 2 patients (18.18%), pulmonary infection and pleural effusion in 2 patients (18.18%), and echinococcosis recurrence in 1 patient (9.09%). Of all 11 patients, 2 (18.18%) died during the perioperative period, and the other 9 patients (81.82%) were improved and discharged. Conclusion Bleeding, biliary complications, and infection are the main causes of death in patients undergoing autologous liver transplantation at high altitude. An accurate understanding of surgical indication, careful multidisciplinary evaluation before surgery, superb operation during surgery, standardized surgical procedures, and fine perioperative management are the key to reducing perioperative mortality, avoiding and reducing postoperative complications, and achieving good long-term survival in patients undergoing autologous liver transplantation.

Objective To compare the clinical efficacy of transdorsal-to-plantar (TDP) or transplantar-to-dorsal (TPD) retrograde endovascular angioplasty in treating below-the-knee arterial occlusion diseases, and to compare it with conventional anterograde endovascular angioplasty. Methods A total of 96 patients with below-the-knee arterial occlusion diseases (112 diseased lower extremities in total), who were admitted to authors’ hospital during the period from Oct. 2009 to July 2011 to receive conventional anterograde endovascular angioplasty, were enrolled in this study. The clinical data were retrospectively analyzed. Among the 112 diseased lower extremities, conventional anterograde endovascular angioplasty failed in 27, and TDP or TPD retrograde endovascular angioplasty had to be carried out. A total of 71 patients (85 diseased lower limbs) were successfully treated with conventional anterograde endovascular angioplasty (routine group), while 20 patients (22 diseased lower limbs) were successfully treated with retrograde endovascular angioplasty (retrograde group). The preoperative ankle-brachial index(ABI), the coronary angiography-based thrombolysis in myocardial infarction (TIMI) flow score, the dorsal or plantar arterial pulse score, the postoperative limb salvage rate and target vessel patency rate were calculated, and the results were compared between the two groups. Results The technical success rate in the retrograde group and the routine group was 75.9% and 74.0%respectively (P>0.05). Preoperative ABI value of the retrograde group and the routine group was 0.55± 0.21 and 0.56±0.14 respectively, after the treatment which increased to 0.93±0.19 and 0.89±0.18 respectively (P>0.05). Preoperative TIMI score of the retrograde group and the routine group was 0.1 ±0.5 and 0.8 ±0.8 respectively, which significantly increased to 2.5±0.6 and 1.8±0.8 respectively (P<0.000 1). In the retrograde group, the blood flow perfusion of the distal foot tissue was improved. The primary target vessel patency rate at 12 months and 24 months after the treatment in the retrograde group and the routine group were 63.6%(14/22), 45.5%(10/22) and 52.9%(45/85), 37.6%(32/85) respectively (P>0.05). Twenty-four months after endovascular angioplasty Kaplan-Meier analysis indicated that the limb salvage rate of the retrograde group and the routine group was 95.5%and 96.5%respectively (P>0.05). Conclusion Compared with conventional anterograde endovascular angioplasty for the treatment of below-the-knee arterial occlusion diseases, retrograde endovascular angioplasty via TDP or TPD path can immediately improve the blood flow with obvious improvement of ABI score, primary target vessel patency rate as well as the limb salvage rate. Therefore, retrograde endovascular angioplasty should be regarded as an effective supplementary technique when anterograde angioplasty fails.

Objective To study the defects of bone marrow-derived endothelial progenitor cells (EPCs) in number ratio and biological abilities (proliferation, adhesion and migration) in diabetic rats. Methods (1) Establishment of diabetic rat model:1%STZ solution was quickly injected into the abdominal cavity of the male SD rats with the dose of 60 mg/kg. (2). Isolation, culture and identification of bone marrow-derived EPCs in diabetic and normal rats. Bone marrow mononuclear cells were isolated from diabetic and normal rats by density gradient centrifugation methods and cultured by EGM-2 MV medium. The cells were identified by morphological observation, FITC-UEA-1 binding and Dil-Ac-LDL uptake assay, and fluorescent immunocytochemistry was used for detection of CD34 , CD133 and VEGFR-2 expression. CCK-8 method and Transwell kit method were used to determine biological activities of EPCs. Results (1) When cultured in vitro, both bone marrow-derived EPCs in diabetic and normal rats were fusiform in shape, the cells snuggled up to the wall. The expression of CD34, CDl33, VEGFR-2 could be detected in these cells, and the cells could uptake Dil-Ac-LDL and bind FITC-UEA-1, which proved that these cells were EPCs. (2) No significant difference in the number of EPCs derived from bone marrow existed between diabetic rats and normal rats, but the proliferation ability, migration ability and adhesion ability of bone marrow-derived EPCs in diabetic rats were obviously lower than those in normal rats. Conclusion The number of bone marrow-derived EPCs in diabetic rats is not obviously different from that in normal rats, but the biologic activity of EPCs derived from bone marrow in diabetic rats is degraded, which is manifested as weakened abilities of the proliferation, adhesion and migration.

A 46-year-old female patient presented to our hospital with history of pharyngeal discomfort for 6 months. Physical examination showed that she had facial asymmetry, loss of the left nasolabial fold, rightward de- viation of uvula, swelling of the left soft palate. Magnetic resonance imaging revealed a bigger neoplasm in left pa- rapharyngeal space which invaded into left lateral skull base. The left internal carotid artery, vein and the styloid process was jostled backward. The primary clinical diagnosis is pleomorphic adenoma of the parapharyngeal space.
Adenoma, Pleomorphic ; surgery ; Carotid Artery, Internal ; Endoscopes ; Endoscopy ; Face ; abnormalities ; Facial Asymmetry ; congenital ; Female ; Humans ; Hyperplasia ; Magnetic Resonance Imaging ; Middle Aged ; Nasal Cavity ; Paranasal Sinuses ; Pharynx ; Skull Base Neoplasms ; surgery

Objective To investigate the association of single nucleotide polymorphisms (SNPs) in the SCGB3A2(secretoglobin family 3A member 2) gene promoter with susceptibility of Graves' disease.Methods One-hundred and seventy-nine SNPs within a 3.0 Mb region surrounding marker D5s2090 were scanned in a case-control study.The size of the region(s) associated with GD was then narrowed.Results Total 179 SNPs within a 3.0 Mb region surrounding marker D5s2090 were analyzed.The most significant association signal was found at SNP rs1368408 (P =3.69 × 10-5).Subsequent association analysis was then performed and the results suggested that the SNP76 (P =4.11 × 10-8) and SNP75 (P =1.37 × 10-8) in the promoter of SCGB3A2 gene may be the causal variants of GD.Logistic regression analysis suggested these 2 SNPs in this region may contribute to GD susceptibility.Conclusion A significant association seems to exist between GD with the SCGB3A2 gene.

Objective To discuss the technical points, safety and clinical effectiveness of DSA-guided percutaneous acetabuloplasty (PA) for the treatment of acetabular metastases. Methods Fifteen patients, including 6 males and 9 females, with acetabular malignant metastases were enrolled in this study.A total of 19 lesions were detected. The lesions were 13 - 25 mm in size (mean 19 ± 4 mm), the dose of PMMA used for per lesion was 5 - 13 ml (mean 8.2 ± 2.3 ml). All patients complained of greater or less degree of pain in their hips, 8 patients had to use walking stick, 4 patients showed limping although they could walk independently and three patients could not walk alone. DSA-guided percutaneous acetabuloplasty was performed in all patients and follow-up after the procedure was conducted for 1 - 12 months. Visual analogue score (VAS), walking state score and analgesic dosage taken by the patients were used for the evaluation of the clinical effectiveness. The complications were analyzed. All the data obtained were statistically analyzed with paired samples t test and analysis of variance by using SPSS12.0 statistical software.Results The procedure was technically successful in all patients. Pain rating evaluated by the VAS decreased from a mean of 7.8 before surgery to a mean of 4.2 in 24 hours after surgery (P < 0.01 ), which further decreased to 2.5 in one month (P < 0.01 ), while walking state score increased from a mean of 1.5before surgery to a mean of 2.5 in 24 hours after surgery (P < 0.01 ). The analgesic dosage taken by the patient was reduced in 14 patients and remained the same in one patient. The bone cement leakage into paraacetabular soft tissues occurred in three cases and peripheral vascular exudation of acetabulum was observed in three cases with no obvious clinical symptoms. Conclusion As a safe, reliable and minimally-invasive technique, DSA-guided percutaneous acetabuloplasty has excellent anti-pain effect in treating acetabular metastases. This therapy can markedlyimprove the patient's walking ability and the quality of life.