Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective:To evaluate the clinical outcomesof primary reverse total shoulder arthroplasty (RTSA) and revision procedure with RTSA after treatment failure of complex proximal humeral fractures in the elderly.Methods:A retrospective analysis was conductedon 24 elderly patients with Neer three- or four-part proximal humeral fractures who underwent RTSA revision after treatment failure (RTSA revision group) from January 2017 to June 2022. There were 7 males and 17 females included, with a mean age of 78.23±5.78 years (range, 67-86 years). Forty-eight patients who underwent primary RTSA (primary RTSA group) during the same time period were selected by propensity score matchingin a 1∶2 ratio as controls, based on age, dominanthand, etiology, Neer typing, glenohumeral joint dislocation, rotator cuff integrity, and osteoporosis T-score. The primary RTSA group included 12 males and 36 females, with a mean age of 76.38±6.15 years (range, 65-87 years). Clinical indicators including demographic characteristics, healing rate of the greater tuberosity, visual analogue score (VAS), Constant-Murley score, American Shoulder and Elbow Surgeons (ASES), shoulder range of motion (ROM), patient satisfaction, and complication rate were collected and analyzed.Results:The mean follow-up duration was 40(32, 60) months (range, 25-72 months) in the primary RTSA group and 38(30, 61) months (range, 24-68 months) in RTSA revision group. There was no significant difference (χ 2=5.058, P=0.168) in the healing rate of the greater tuberosity between the primary RTSA group (41/48, 85.4%) and the RTSA revision group (15/24, 62.5%). Compared with preoperative status, the ROM of anterior elevation, abduction supination, external rotation, VAS score, Constant-Murley score, and ASES score were significantly improved at the last follow-up (all P<0.05) in the RTSA revision group. The anterior elevation (123.74°± 16.57°), abduction supination (113.73°±16.42°), and external rotation (36.45°±10.36°) in the primary RTSA group were superior to those in the RTSA revision group (109.43°±18.75°, 98.64°±15.47°, 30.47°±10.64°, respectively), the difference was statistically significant ( P<0.05). No statistical difference of ROM of internal rotation between the two groups was found (χ 2=4.034, P=0.133). At the last follow-up, the Constant-Murley scores (75.47±11.66) and ASES scores (73.58±15.72) of the primary RTSA group were higher than those in the RTSA revision group (60.43±10.24 and 63.28±18.77, respectively), and the differences were statistically significant ( P<0.05). In terms of VAS (1.66±0.93 vs. 2.02±1.15) and patient satisfaction [83%(40/48) vs. 88%(21/24)], no statistical difference was identified ( P>0.05). The complication rate were 10.4% (5/48) in the primary RTSA group and 20.8% (5/24) in the RTSA revision group (χ 2=1.452, P=0.285), with no serious complications requiring revision surgery in either group. Conclusions:For elderly patients with proximal humeral fractures after failed operation, RTSA revision might effectively improve the limb function and alleviatepain. However, compared with RTSA revision, primary RTSA demonstrated superiorearly clinical outcomes in shoulder ROM and functional recovery.

This study was aimed at understanding the resistance status of dairy cow-derived Streptococcus strains in China,and providing scientific guidance for the rational use of antimicrobials and the development of new antimicrobials.Meta-analysis was used to explore the resistance of Streptococcus strains to 20 antimicrobials between 2000 and 2023.A total of 67 articles de-scribing 3 154 strains were included after a literature search,and a meta-analysis was conducted on the overall collection area according to time subgroups for 20 antimicrobials.Streptococci of dairy origin in China showed varying resistance rates(≥30％),as follows:penicillin(60％,95％CI=0.48-0.72),streptomycin(57％,95％CI=0.46-0.68),cotrimoxazole(56％,95％CI=0.28-0.82),lincomycin(51％,95％CI=0.26-0.76),tetracycline(49％,95％CI=0.40-0.59),doxycyc-line(42％,95％CI=0.24-0.60),clindamycin(41％,95％CI=0.28-0.54),ampicillin(39％,95％CI=0.27-0.52),e-rythromycin(37％,95％CI=0.28-0.45),kanamycin(36％,95％CI=0.20-0.54),and amoxicillin(30％,95％CI=0.10-0.53).On the basis of findings in the collection area,the resistance rates of dairy cow-derived Streptococcus to antimicrobials in Northeast China and Southwest China was generally high.The resistance rates of Streptococcus from dairy cattle to antimi-crobial drugs such as tetracycline,doxycycline,and lincomycin increased significantly over time.However,the resistance rates to antimicrobial drugs such as streptomycin,gentamicin,and enrofloxacin showed a significant decreasing trend.Dairy cow-de-rived Streptococcus had high resistance to some antimicrobials,and the resistance varied by region,because of differences in breeding and management.Monitoring of antimicrobial resistance rates,enhancing research on resistance mechanisms,and reg-ulating the use of antimicrobials remain necessary.

Objective To evaluate the efficacy and safety of a novel intravascular lithotripsy(IVL)balloon—Vesscrack shockwave balloon—for vascular preparation before stent implantation in patients with severe coronary artery calcification(CAC).Methods This was a prospective,single-arm,multicenter study conducted in China from June 2022 to October 2022.Patients with severe CAC were treated with the Vesscrack shockwave balloon for lesion preparation,followed by drug-eluting stent(DES)implantation.Of these,33 patients underwent optical coherence tomography(OCT).The primary endpoint was procedural success,defined as successful stent implantation with residual stenosis≤30％and the absence of in-hospital major adverse events,including cardiac death,target vessel-related myocardial infarction,or target lesion revascularization.Results A total of 170 patients[mean age:(65.9±7.9)years,116 males]were enrolled.After treatment with IVL and DES,the minimum lumen diameter increased significantly compared to baseline[(2.34±0.40)mm vs.(0.95±0.33)mm,P＜0.001],the degree of stenosis was significantly reduced[(13.24±6.60)％vs.(65.18±10.59)％,P＜0.001].Procedural success was achieved in 100％of cases,and device success was 98.8％.The 30-day patient-related cardiovascular clinical composite endpoint(POCE)rate was 0.0,with no target lesion failure,no confirmed or potential thrombotic events were observed.The shockwave energy generator demonstrated excellent stability and ease of use.Among the 33 patients assessed with OCT,after IVL intervention,the maximum calcified area of the lumen[(3.51±1.51)mm2 vs.(2.85±1.80)mm2,P＜0.001],and the minimum lumen area within the target lesion[(3.08±1.04)mm2 vs.(2.02±0.75)mm2,P＜0.001],and after DES intervention,the luminal area of the largest calcified site[(6.59±1.64)mm2 vs.(2.85±1.80)mm2,P＜0.001]and the minimum luminal area within the target lesion[(6.19±1.45)mm2 vs.(2.02±0.75)mm2,P＜0.001]were significantly increased,and the differences were statistically significant.Conclusions The Vesscrack shockwave balloon is effective and safe for vascular preparation in patients with severe CAC prior to stent implantation.It achieves significant calcified plaque modification,high procedural success rates,and minimal complications.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective:To evaluate the clinical outcomesof primary reverse total shoulder arthroplasty (RTSA) and revision procedure with RTSA after treatment failure of complex proximal humeral fractures in the elderly.Methods:A retrospective analysis was conductedon 24 elderly patients with Neer three- or four-part proximal humeral fractures who underwent RTSA revision after treatment failure (RTSA revision group) from January 2017 to June 2022. There were 7 males and 17 females included, with a mean age of 78.23±5.78 years (range, 67-86 years). Forty-eight patients who underwent primary RTSA (primary RTSA group) during the same time period were selected by propensity score matchingin a 1∶2 ratio as controls, based on age, dominanthand, etiology, Neer typing, glenohumeral joint dislocation, rotator cuff integrity, and osteoporosis T-score. The primary RTSA group included 12 males and 36 females, with a mean age of 76.38±6.15 years (range, 65-87 years). Clinical indicators including demographic characteristics, healing rate of the greater tuberosity, visual analogue score (VAS), Constant-Murley score, American Shoulder and Elbow Surgeons (ASES), shoulder range of motion (ROM), patient satisfaction, and complication rate were collected and analyzed.Results:The mean follow-up duration was 40(32, 60) months (range, 25-72 months) in the primary RTSA group and 38(30, 61) months (range, 24-68 months) in RTSA revision group. There was no significant difference (χ 2=5.058, P=0.168) in the healing rate of the greater tuberosity between the primary RTSA group (41/48, 85.4%) and the RTSA revision group (15/24, 62.5%). Compared with preoperative status, the ROM of anterior elevation, abduction supination, external rotation, VAS score, Constant-Murley score, and ASES score were significantly improved at the last follow-up (all P<0.05) in the RTSA revision group. The anterior elevation (123.74°± 16.57°), abduction supination (113.73°±16.42°), and external rotation (36.45°±10.36°) in the primary RTSA group were superior to those in the RTSA revision group (109.43°±18.75°, 98.64°±15.47°, 30.47°±10.64°, respectively), the difference was statistically significant ( P<0.05). No statistical difference of ROM of internal rotation between the two groups was found (χ 2=4.034, P=0.133). At the last follow-up, the Constant-Murley scores (75.47±11.66) and ASES scores (73.58±15.72) of the primary RTSA group were higher than those in the RTSA revision group (60.43±10.24 and 63.28±18.77, respectively), and the differences were statistically significant ( P<0.05). In terms of VAS (1.66±0.93 vs. 2.02±1.15) and patient satisfaction [83%(40/48) vs. 88%(21/24)], no statistical difference was identified ( P>0.05). The complication rate were 10.4% (5/48) in the primary RTSA group and 20.8% (5/24) in the RTSA revision group (χ 2=1.452, P=0.285), with no serious complications requiring revision surgery in either group. Conclusions:For elderly patients with proximal humeral fractures after failed operation, RTSA revision might effectively improve the limb function and alleviatepain. However, compared with RTSA revision, primary RTSA demonstrated superiorearly clinical outcomes in shoulder ROM and functional recovery.

Objective:To evaluate the clinical efficacy of transoral robotic surgery (TORS) in the treatment of malignant tongue base tumors.Methods:A multicenter study was conducted to collect and analyze the clinical data of patients with malignant tongue base tumors who underwent TORS at five otolaryngology-head and neck surgery centers in China, including Eye Ear Nose and Throat Hospital of Fudan University, Sun Yat-sen University Cancer Center, Tongji Hospital of Huazhong University of Science and Technology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, and the First Affiliated Hospital of China Medical University between January 2017 and January 2023. Among the patients, 38 were males and 11 were females, with a mean age of 59.0±8.8 years. Baseline characteristics, complications, and follow-up data were compared between groups. Independent sample t-tests or Mann-Whitney U tests was used for comparisons of continuous variables; chi-square tests or Fisher′s exact tests was applied for categorical variables. Survival analysis was performed using the Kaplan-Meier method to calculate overall survival and disease-free survival, and differences between groups were compared using the log-rank test. Results:Among the 49 patients, 41 (83.7%) were diagnosed with squamous cell carcinoma (SCC), with a p16 positive rate of 51.2% (21/41). There were no statistically significant differences between the p16-positive group ( n=21) and the p16-negative group ( n=20) in age, sex, or postoperative bleeding (all P>0.05). However, there was a significant difference in TNM stage between the two groups ( χ2=14.556, P=0.020), with the p16-positive group predominantly in stage I (66.7%) and the p16-negative group primarily in stages Ⅲ and Ⅳ (40.0% and 30.0%, respectively). The postoperative tracheotomy rate was 30.6% (15/49), and the incidence of postoperative bleeding was 6.1% (3/49). The 1-year and 3-year overall survival rates were 98.0% and 92.5%, respectively, while, the 1-year and 3-year disease-free survival rates were 89.2% and 84.9%, respectively. No significant differences were observed between the p16-positive and p16-negative groups in 3-year overall survival (100% vs. 83.8%, χ2=1.093, P=0.518) or 3-year disease-free survival (68.2% vs. 88.9%, χ2=2.161, P=0.382). Conclusion:TORS for malignant tongue base tumors demonstrates high clinical safety and favorable oncological outcomes.

Objective:To explore the clinical application value of transoral robotic surgery (TORS) in the treatment of tonsil squamous cell carcinoma (TSCC).Methods:A retrospective analysis was conducted. The clinical data of 157 TSCC patients were collected who received TORS at five medical centers, namely, the Sun Yat-sen University Cancer Center, Sun Yat-sen Memorial Hospital, Eye Ear Nose and Throat Hospital of Fudan University, the First Affiliated Hospital of China Medical University, and Tongji Hospital of Tongji Medical College, from January 1 2017 to July 31 2022. There were 130 males and 27 females, aged 24-85 years. All patients were followed-up at least for 2 years (2-year group), among them, 99 patients had a follow-up of 3 years (3-year group). The overall survival (OS), progression-free survival (PFS), clinical stage, human papillomavirus (HPV) infection status were analyzed. SPSS 25.0 and SAS 9.4 were used for statistical analysis.Results:The OS and PFS of the 2-year group were 91.7% and 87.9%, respectively. The OS and PFS of the 3-year group were 85.9% and 82.8%, respectively. The prognosis of patients with locally early-stage was better than that of locally advanced patients, with the OS of 94.4% for T1-2 vs. 78.0% for T3 ( P=0.005) and the PFS of 91.2% for T1-2 vs. 75.0% for T3 ( P=0.011) in the 2-year group; the OS of 91.1% for T1-2 vs. 65.0% for T3 ( P=0.004) and the PFS of 88.6% for T1-2 vs. 60.0% for T3 ( P=0.002) in the 3-year group; and also, the OS of 90.0% for stage Ⅰ-Ⅱ vs. 79.5% for stage Ⅲ-Ⅳ ( P=0.204) and the PFS of 86.7% for stage Ⅰ-Ⅱ vs. 76.9% for stage Ⅲ-Ⅳ ( P=0.188) in the 3-year group. The prognosis of HPV-positive TSCC patients was better than that of HPV-negative patients in the 3-year group, with the OS of 90.9% for HPV-positive vs. 80.5% for HPV-negative ( P=0.045) and the PFS of 90.9% for HPV-positive vs. 75.6% for HPV-negative ( P=0.047). The average time of postoperative tracheal cannula indwelling was 25.1 days. The indwelling rate and average indwelling time of the postoperative nasogastric tube were 94.3% (148/157) and 8.5 days, respectively. Conclusion:TORS has outstanding survival benefits for TSCC patients. HPV-positive TSCC patients have a better prognosis than HPV-negative patients. TORS treatment of TSCC patients has advantages in postoperative recovery and quality of life.

Objective:To investigate the efficacy and feasibility of transoral robotic surgery (TORS) for resection of tumors in the parapharyngeal spaces.Methods:The clinical data of 57 patients who underwent TORS for parapharyngeal space tumors from September 2018 to February 2024 were retrospectively analyzed. These patients were treated at five medical institutions: The First Affiliated Hospital of China Medical University, Eye & ENT Hospital of Fudan University, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, and Sun Yat-sen University Cancer Center. The patients were 28 males and 29 females, aged 17-77 years (median age, 47 years). The pathological types, locations, and sizes of the tumors, operation time, intraoperative bleeding volumes, postoperative hospital stays, and postoperative complications were evaluated. The data were analyzed using SPSS 27.0 software.Results:Postoperative pathological examination revealed 11 types of benign tumors. Among 57 cases, 27 cases had their tumors in the prestyloid spaces, predominantly with pleomorphic adenoma ( n=17), and 30 cases in the retrostyloid spaces, predominantly with schwannoma ( n=22). The tumor volumes ranged from 0.6 to 130.1 cm3, the intraoperative bleeding volumes ranged from 5 to 1 000 ml, the operation time ranged from 20 to 390 min, and the postoperative hospital stays ranged from 2 to 25 days. The total costs for individual cases were 36 000-100 000 yuan, with the highest cost in the case suffering from cerebrovascular accident. Four patients(7.0%) had tracheotomy and 36(63.2%) had nasogastric tube placement. Among the 57 patients, 5 had postoperative cavity effusion, 2 had wound dehiscence, 2 had cerebrovascular accidents, 1 had Horner syndrome, and 2 had other complications. The patients were followed up for 1-67 months, with only 1 patient with intracranial and extracranial communication relapsed. Conclusion:TORS is a safe and feasible approach for treating parapharyngeal space tumors, offering advantages such as minimal invasiveness, reduced blood loss, and faster recovery. It is suitable for parapharyngeal space tumors of various pathological types and locations. The postoperative complications are manageable, with favorable long-term follow-up results and low recurrence rates.

Purpose To investigate the incidence and risk of malignancy(ROM)of the Bethesda class Ⅰ/Ⅲ di-agnosis of thyroid nodules due to insufficient number of follicular cells,and to analyze the correlation between their in-sufficient cell volume and the characteristics of the nodules themselves from the perspective of ultrasound and histology.Methods Clinical data were collected from fine needle aspiration cytology(FNAC)of the thyroid gland.Review and statistical analysis was performed on cases with the Bethesda class Ⅰ/Ⅲ diagnosis due to insufficient cell volume.The incidence and the ROM of Bethesda class Ⅰ/Ⅲ diagnosis were calculated.BRAF V600E(+)or postoperative patho-logical indicating papillary thyroid carcinoma(PTC)was used as the criterion for malignancy.Then,we matched the Bethesda class Ⅱ/Ⅵ cases with sufficient cell volume as the control group.The ultrasound characteristics and histo-logical images of the two groups were compared and analyzed in order to reveal the correlation between the insufficient amount of penetrating cells and the objective characteristics of the nodule itself.Results There were 39 solid thyroid nodules with the Bethesda class Ⅰ diagnosis,with an incidence of 3.3％and a ROM of 38.5％,and 160 nodules with the Bethesda class Ⅲ diagnosis,with an incidence of 13.5％and a ROM of 59.4％.The incidence and ROM of nod-ules with C-TIRADS ≥4b(22.4％,67.6％)were higher than those of C-TIRADS ≤4a(12.7％,39.8％),and the differences were statistically significant(P＜0.001).Compared to the Bethesda class Ⅱ/Ⅵ nodules with sufficient cell volume,occurrence of the Bethesda class Ⅰ/Ⅲ nodules were significantly correlated with small nodules(maximal diameter＜5 mm),vertical growth(aspect ratio ≥ 1)and poor blood supply(no or little blood flow signals)(r=0.131,-0.230,0.237,P=0.008,＜0.001,＜0.001).They were also significantly correlated with the pathologic histologic structure of diffuse significant fibrosis of the interstitium and low parenchyma/interstitium composition ratio(about 1:1)(r=-0.269,-0.396,P=0.019,＜0.001).Conclusion Thyroid Bethesda class Ⅰ/Ⅲ nodules have a high ROM,and BRAF V600E detection is recommended as a tool of tiered management.Bethesda class Ⅰ/Ⅲ diagnosis of insufficient cell volume is more likely when the nodules are too small,grow vertically and lack blood sup-ply,presumably associated with extensive interstitial fibrosis and sparse parenchymal cells.