Cabozantinib, mainly targeting cMet and vascular endothelial growth factor receptor 2, is the second-line treatment for patients with advanced hepatocellular carcinoma (HCC). However, the lower response rate and resistance limit its enduring clinical benefit. In this study, we found that cMet-low HCC cells showed primary resistance to cMet inhibitors, and the combination of cabozantinib and mammalian target of rapamycin (mTOR) inhibitor, rapamycin, exhibited a synergistic inhibitory effect on the in vitro cell proliferation and in vivo tumor growth of these cells. Mechanically, the combination of rapamycin with cabozantinib resulted in the remarkable inhibition of AKT, extracellular signal-regulated protein kinases, mTOR, and common downstream signal molecules of receptor tyrosine kinases; decreased cyclin D1 expression; and induced cell cycle arrest. Meanwhile, rapamycin enhanced the inhibitory effects of cabozantinib on the migration and tubule formation of human umbilical vascular endothelial cells and human growth factor-induced invasion of cMet inhibitor-resistant HCC cells under hypoxia condition. These effects were further validated in xenograft models. In conclusion, our findings uncover a potential combination therapy of cabozantinib and rapamycin to combat cabozantinib-resistant HCC.
Anilides/pharmacology* ; Animals ; Carcinoma, Hepatocellular/drug therapy* ; Cell Line, Tumor ; Cell Proliferation ; Endothelial Cells/metabolism* ; Humans ; Liver Neoplasms/drug therapy* ; Pyridines/pharmacology* ; Sirolimus/pharmacology* ; Xenograft Model Antitumor Assays

Objective:To analyze the clinical characteristics of adult Chinese patients with syncope.Methods:This is a cross-sectional survey study. Patients with preliminary diagnosis of syncope in the Emergency Department, Geriatrics and Cardiology Outpatient Department, or Syncope Unit of 37 hospitals in 19 provinces, autonomous regions and the Hong Kong Special Administrative Region from June 2018 to March 2021 were included in this study. The clinical features of these patients with syncope were analyzed.Results:A total of 4 950 consecutive patients with syncope were included in this study. The age was (56.3±16.8)years, and 2 604 cases (52.6%) were male. The most common type of syncope was neurally mediated syncope (2 345 (47.4%)), followed by cardiac syncope (1 085 (21.9%)), orthostatic hypotensive syncope (311 (6.3%)), and unexplained syncope accounted for nearly one third (1 155 (23.3%)). Predisposing syncope was more common in patients under 65 years of age(2 066(72.4%) vs. 786(27.6%),χ 2=136.5, P<0.001). Presyncope was more common in patients with neurally mediated syncope (1 972(79.0%) vs.1 908(73.9%), χ 2=17.756, P<0.001). Premonitory symptoms were more common in women(1 837(80.0%) vs. 1 863(73.0%),χ 2=33.432, P<0.001). Presyncope syndrome was more common in patients under 65 years of age (2 482(77.8%) vs. 1 218(73.4%),χ 2=17.523, P=0.001). Cyanosis was more common in ≥65 years old patients (271(18.2%) vs. 369(12.7%), χ 2=23.235, P<0.001). Urinary incontinence was more common in old patients aged ≥65 years(252(15.2%) vs. 345(10.8%), χ 2=19.313, P<0.001). Family history was more common in patients with cardiogenic syncope compared with other types of syncope (264(24.3%) vs. 754(19.5%), χ 2=11.899, P=0.001). Hypertention(1 480(30.5%)), coronary heart disease(1 057(21.4%)), atrial flutter and atrial fibrillation(359(7.2%)), second degree atrioventricular block(236(4.8%)) were common complications of syncope. The proportion of patients with coronary heart disease was significantly higher in cardiac syncope than that of other types of syncope(417(38.4%) vs. 640(16.6%), χ 2=241.376, P<0.001). Other common complications included cerebrovascular diseases (551 (11.1%)) and diabetes mellitus (632(12.8%)). Conclusions:Neurally mediated syncope is the most common syncope in adult Chinese population. Patients with predisposing conditions and premonitory conditions are younger. Presyncope is more common in women. The proportion of family history and coronary heart disease is higher in patients with cardiogenic syncope.

Objective:To introduce a new operative technique of mini-invasive plating of midshaft clavicle fractures with lateral clavicle anatomic locking plate and evaluate its clinical outcomes.Methods:From August 2017 to March 2019, 30 midshaft clavicular fracture patients were included in this study and retrospectively analyzed. There were 22 males and eight females with an average of 44.63±13.22 years (range 14-65 years). According to Robinson classification nine patients were classified as Type 2A2, 17 patients were classified as Type 2B1 and four patients were classified as Type 2B2. Before operation no symptoms of neurovascular injury was observed in this group. Operations were performed on an average of 2.33±1.75 d (range 0-7 d) after the injury. By comparing the injured clavicle lengths with the opposite healthy side pre and postoperatively on anteroposterior chest x-ray to evaluate the effect of indirect reduction. Shoulder function was evaluated using the Constant-Murley score at 6th month after the operation. Meanwhile, 32 patients with midshaft clavicular fracture treated with open reduction and internal fixation using clavicle reconstruction locking plate treated by the same group surgerons were compared in incision length, surgical duration, intraoperative fluoroscopy times, blood loss, fracture reduction, fracture healing time, Constant-Murley score and other complications. There were 25 males and seven females with an average of 42.63±14.18 years (range 16-70 years). According to Robinson classification six patients were classified as Type 2A2, 19 patients were classified as Type 2B1 and seven patients were classified as Type 2B2.Results:In mini-invasive group all patients were treated successfully with minimally invasive percutaneous osteosynthesis (MIPO) technique using lateral clavicle anatomic locking plate. The mean surgical duration was 63.40±7.82 minutes (range 48-92 min), The mean intraoperative fluoroscopy was 4.83±1.58 times (range 3-8 times). The mean blood lose was 15.67±4.13ml (range 10-30 ml). In open reduction group the mean surgical duration was 56.22±10.11 min (range 42-80 min), the mean intraoperative fluoroscopy was 3.91±1.49 times (range 2-5 times). The mean blood lose was 56.88±13.93 ml (range 40-100 ml). There was a significant difference in statistic by comparing surgical duration, intraoperative fluoroscopy times, blood loss ( P<0.05). In mini-invasive group the average proportional difference of the clavicular length was 12.15%±2.69% (range 5.2%-15.1%) preoperative and 0.45%±0.44% (range -0.2%-1.6%) postoperative comparing with the opposite healthy side, in open reduction group the average proportional difference of the clavicular length was 11.58%±2.67% (range 4.5%-16.1%) preoperative and 0.62%±0.41% (range -0.2%-1.2%) postoperative comparing with the opposite healthy side. There was no difference in statistic by comparing the fracture reduction in these two groups ( P>0.05). The mean follow-up period was 11.3±2.8 months (range 10-18 months) in mini-invasive group. Radiographic healing of the fracture was achieved at a mean time of 3.57±0.90 months (range 3-5 months). In open reduction group the mean follow-up period was 11.8±2.2 months (range 10-18 months), fracture healing time was 4.27±1.12 months (range 3-6 months), and there was significant difference in fracture union ( P<0.05). In mini-invasive group the mean total incision length was 2.8±0.48 cm (range 2.5-4.0 cm), no patient complained of numbness or paresthesia on subclavicular region or anterior chest wall, and all patients were satisfied with the cosmesis of the wounds and showed excellent shoulder joint function with a mean Constant-Murley score of 94.83±2.55 (range 89-97) at sixth month after the operation. In open reduction group the mean incision length was 11.0±1.08 cm (range 10-14 cm), 9 patients complained of numbness or paresthesia on subclavicular region or anterior chest wall, and only 5 patients were satisfied with the cosmesis of the wounds with a mean Constant-Murley score of 90.59±4.23 (range 78-97). There was a significant difference in statistic by comparing incision length, satisfactory cosmesis results, Constant-Murley score and paresthesia on subclavicular region ( P<0.05). Conclusion:Mini-invasive percutaneous plating of midshaft clavicle fractures with lateral clavicle anatomic locking plate is a good option for the treatment of midshaft clavicle fractures with satisfactory cosmesis results and excellent return to function.

Objective: To introduce the surgical method of lateral dorsalis pedis chain-linked artery based flap for repairing foot, ankle, and posterior heel wounds, and to evaluate its clinical outcome. Methods: From June 2013 to February 2016, 11 cases with skin defects of foot, ankle, and posterior heel wounds were reviewed. The defects were repaired using the lateral dorsalis pedis chain-linked artery based flap.The wounds in 7 cases were repaired using the island flap based on the descending branch of the anterior lateral malleolar artery. The wounds in 3 cases were repaired using the island flap based on the lateral calcaneal branch of the posterior lateral malleolar artery. The reversed flap based on the forth metatarsal artery was used in one patient. The wound defects ranged from 1.5 cm×2.0 cm to 6.0 cm×13.0 cm.The area of the flap ranged from 2 cm×3 cm to 7 cm×15 cm were used to repair the wound.The donor site was skin grafted with split-thickness skin harvested from the abdomen. Results: Circulations of the all 11 cases were stable, with good wound healing after 2 weeks.10 patients had clinical follow-up. The patients were followed up from 2 months to 18 months, average of 8 months.All flap grafts survived with no bloated menifestion in pedical or "cat′s ear" deformity.Flaps were soft. Color was consistent with normal skin.Skin graft donor sites had no obvious scars.Patients were extremely satisfied with the result of repair. Conclusions The use of the lateral dorsalis pedis chain-linked artery based flap has many advantages, such as no sacrifice of the main vessels, extended coverage area and thin flap. It is a simple and effective method to repair wounds of the foot, ankle, and posterior heel.

Objective To systematically evaluate the short-term outcomes of laparoscopic splenectomy and azygoportal disconnection (LSD) with open splenectomy and azygoportal disconnection (OSD) in the prevention and treatment of portal hypertension (PHT) hemorrhage.Methods A meta-analysis was conducted to evaluate the short-term outcomes published in randomized controlled studies and high quality casecontrolled studies on patients who underwent LSD or OSD from January 2006 to January 2016.Results 1 359 patients from 18 Chinese and English articles which met the inclusion criteria were included into this study.LSD and OSD were performed in 685 patients (the LSD group) and 674 patients (the OSD group),respectively.Meta-analysis showed that there was no significant difference in operation time between the LSD and OSD groups [MD=17.66,95％CI=(-2.46 ～37.78),P＞0.05].When compared with the OSD group,the LSD group had a shorter postoperative hospitalization stay [MD =-3.99,95％ CI =(-4.82 ～ -3.16),P ＜ 0.05],earlier postoperatively first passing of flatus [MD =-1.09,95％ CI =(-1.41 ～ -0.78),P ＜ 0.05],less intraoperative bleeding [MD =-272.66,95％ CI =(-345.11 ～-200.21),P ＜ 0.05],a lower complication rate [OR =0.34,95％ CI =(0.25 ～ 0.47),P ＜ 0.05],less postoperative pain [MD =-2.54,95％ CI =(-2.79 ～-2.29),P ＜ 0.05],shorter postoperative ambulation time [MD =-3.16,95％ CI =(-3.53 ～-2.79),P ＜ 0.05],less amount of peritoneal drainage [MD =-180.28,95％ CI =(-293.06 ～-67.49),P ＜0.05] and earlier recovery from postoperative loss in appetite [MD =-1.42,95％ CI =(-1.70 ～-1.13),P ＜ 0.05].Conclusion Compared with the traditional OSD,LSD had the advantages of less invasiveness,quicker recovery and higher quality of life in the perioperative period.LSD is the preferred operation for the prevention and treatment of PHT massive hemorrhage.

Objective To introduce an indirect reduction technique using a modified tibial distraction support in minimally invasive percutaneous plate osteosynthesis (MIPPO) of distal femur fractures and investigate its clinical effect.Methods Between April 2014 and March 2016,26 distal femur fractures treated with MIPPO technique using a modified tibial distractionsupport were reviewed.There were 18 males and 8 females with an average age of (50±10.1) years (25-76 years).Among them,nineteen patients were type A and 7 patients were type C according to AO classification.Operations were performed on an average of (5.6±3.1) d (2-14 d) after the trauma.All the patients were performed indirect reduction with a modified tibial distraction support before using the MIPPO technique.Angular deformity was obtained from preoperative and postoperative for all subjects.In each case,intraoperative image intensification shots to confirm reduction and the operating time were recorded.Functional outcome was evaluated using the Schatzker-Lambert criteria 1 year postoperative.Results All the patients completed closed reduction using the modified tibia] distraction support.Preoperative anteroposterior radiographs revealed amean of 8.0°±3.1° (0-16°) angulation in the coronal plane.Lateral radiographs revealed a mean of 16.8°±8.4° (5°-8.6°) angulation in the sagittal plane.Postoperative anteroposterior and lateral radiographs showed a mean angulation of 1.8°±0.6° (0-3.2°) and 2.5°±0.6° (0-3.8°) of varus/valgus and apex posterior angulation,respectively.The mean operating time was (100±11.6) min (80-120 min).No intraoperative or postoperative complications were encountered.Twenty-five patients were followed up and the mean follow up time was (18±3.9) months (12-28 months).There were one delayed union and one non-union.The average time of radiographic evidence of bridging callous was present at (4±0.7) months (3-6 months) in the remained patients.There were 22 excellent patients and 3 good patients according to Schatzker-Lambert criteria one year postoperative.The excellent rate was 100％.Conclusion The modified tibial distraction support is simple and easy to manipulate which is a good option in MIPPO for distal femur fractures and has good clinical effects.

Objective To evaluate the effectiveness of flexor hallucis longus tendon transfer in treatment of chronic Achilles tendinopathy using different technique.Methods Sixty-four embalmed feet of 32 cadavers were analyzed and classified anatomically with respect to the individual cross links in the Henry's knot.These three techniques were then combined to determine the total potential tendon graft length obtainable using single incision,double incision and minimally invasive incision.From January,2012 to June,2015,10 patients (10 feet) with chronic Achilles tendinopathy were treated with double incision technique.The score was 63.04 ±7.75 according to American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot score system.Results Only two different configurations were found.Type 1,a tendinous slip branched from the FHLT to the FDLT was 96.9％(62 of 64 feet).Type 2,a slip branched from the FHLT to the FDLT and another slip from the FDLT to FHLT was 3.1％(2 of 64).The average length of the FHLT graft available from a single incision measured (5.08±1.09)cm,double incision technique measured (6.72 ± 1.02) cm,and minimally invasive incision measured (17.49 ± 1.80)cm.The difference between the lengths obtained from these three techniques was statistically significant.Ten patients were followed-up 12-36 months (mean,13.7 months).At 12 months after operation,the AOFAS ankle and hindfoot score was 93.28 ± 3.72,showing significant difference when compared with that before operation.The results were excellent in 6 cases,good in 3 cases,and fair in 1 case with an excellent and good rate of 90％.No sural nerve injury,posterior tibial nerve injury,medial plantar nerve injury,and lateral plantar nerve injury occurred.Conclusion In over 96 ％ of the feet,a proximal to distal connection from the FHLT to the FDLT was found,which might contribute to the residual function of the lesser toes after FDLT transfer.The distal stump of the FHLT tendon should be sutured onto the FDLT tendon under tension to en able a co-activation of the great toe,preserved hallux plantar flexion.Chronic Achilles tendinopathy reconstruction with flexor hallucis longus tendon harvested using double incision technique offers a desirable outcome in operative recovery,tendon fixation,preserved hallux plantar flexion and less complications.

OBJECTIVETo explore the method of the treatment for hallux valgus with the proximal crescentic osteotomy of the first metatarsal bone, combining with distal lateral soft tissue release.

METHODSFrom January 2008 to December 2012, 21 cases 21 hallux valgus feet were treated by operative procedure, included 1 male (1 foot) and 20 females (20 feet), with the mean age of 52 years (range, 36-68 years). Among all patients were followed up for 12 to 26 months, with the mean 16 months. The preoperative, post-operative and final follow-up X-ray films of all patients were collected. The hallux valgus angle, intermetatarsal angle and distal metatarsal articular angle were measured and analyzed. The surgical outcome was evaluated combined with the AOFAS score.

RESULTSThe average hallux valgus angle decreased from 42.3° ± 1.8° preoperatively to 14.5° ± 1.8 postoperatively, the average intermetatarsal angle did from 21.9° ± 1.7 to 9.1° ± 1.8°, and the average distal metatarsal articular angle did from 14.9° ± 1.8 to 7.2° ± 1.5, respectively. There were significant differences between the preoperative and postoperative roentgenographic index. AOFAS score was improved from 44.0 ± 1.8 preoperatively to 83.9 ± 2.2 at the final follow-up.

CONCLUSIONSThe proximal crescentic osteotomy of the first metatarsal bone combined distal soft tissue reconstruction obtained satisfactory results in severe hallux valgus patients with big intermetatarsal angle.

Adult ; Aged ; Dermatologic Surgical Procedures ; methods ; Female ; Hallux Valgus ; surgery ; Humans ; Male ; Metatarsal Bones ; surgery ; Middle Aged ; Osteotomy ; methods

Objective To explore the method of the treatment for hallux valgus with the proximal crescentic osteotomy of the first metatarsal bone,combining with distal lateral soft tissue release.Methods From January 2008 to December 2012,21 eases 21 hallux valgus feet were treated by operative procedure,included 1 male (1 foot) and 20 females(20 feet),with the mean age of 52 years (range,36-68 years).Among all patients were followed up for 12 to 26 months,with the mean 16 months.The preoperative,postoperative and final follow-up X-ray films of all patients were collected.The hallux valgus angle,intermetatarsal angle and distal metatarsal articular angle were measured and analyzed.The surgical outcome was evaluated combined with the AOFAS score.Results The average hallux valgus angle decreased from 42.3° ± 1.8° preoperatively to 14.5° ± 1.8° postoperatively,the average intermetatarsal angle did from 21.9°±1.7° to 9.1° ± 1.8°,and the average distal metatarsal articular angle did from 14.9° ± 1.8° to 7.2°± 1.5°,respectively.There were significant differences between the preoperative and postoperativeroentgenographic index.AOFAS score was improved from 44.0 ± 1.8 preoperatively to 83.9 ± 2.2 at thefinal follow-up.Conclusions The proximal crescentic osteotomy of the first metatarsal bone combineddistal soft tissue reconstruction obtained satisfactory results in severe hallux valgus patients with bigintermetatarsal angle.

Objective To explore the method of the treatment for hallux valgus with the proximal crescentic osteotomy of the first metatarsal bone,combining with distal lateral soft tissue release.Methods From January 2008 to December 2012,21 eases 21 hallux valgus feet were treated by operative procedure,included 1 male (1 foot) and 20 females(20 feet),with the mean age of 52 years (range,36-68 years).Among all patients were followed up for 12 to 26 months,with the mean 16 months.The preoperative,postoperative and final follow-up X-ray films of all patients were collected.The hallux valgus angle,intermetatarsal angle and distal metatarsal articular angle were measured and analyzed.The surgical outcome was evaluated combined with the AOFAS score.Results The average hallux valgus angle decreased from 42.3° ± 1.8° preoperatively to 14.5° ± 1.8° postoperatively,the average intermetatarsal angle did from 21.9°±1.7° to 9.1° ± 1.8°,and the average distal metatarsal articular angle did from 14.9° ± 1.8° to 7.2°± 1.5°,respectively.There were significant differences between the preoperative and postoperativeroentgenographic index.AOFAS score was improved from 44.0 ± 1.8 preoperatively to 83.9 ± 2.2 at thefinal follow-up.Conclusions The proximal crescentic osteotomy of the first metatarsal bone combineddistal soft tissue reconstruction obtained satisfactory results in severe hallux valgus patients with bigintermetatarsal angle.