A highly tumor-targeted nanoparticle of podophyllotoxin penetrated tumor core and regressed multidrug resistant tumors

Podophyllotoxin (PPT) exhibited significant activity against P-glycoprotein mediated multidrug resistant (MDR) tumor cell lines; however, due to its poor solubility and high toxicity, PPT cannot be dosed systemically, preventing its clinical use for MDR cancer. We developed a nanoparticle dosage form of PPT by covalently conjugating PPT and polyethylene glycol (PEG) with acetylated carboxymethyl cellulose (CMC-Ac) using one-pot esterification chemistry. The polymer conjugates self-assembled into nanoparticles (NPs) of variable sizes (20–120 nm) depending on the PPT-to-PEG molar ratio (2–20). The conjugate with a low PPT/PEG molar ratio of 2 yielded NPs with a mean diameter of 20 nm and released PPT at ∼5%/day in serum, while conjugates with increased PPT/PEG ratios (5 and 20) produced bigger particles (30 nm and 120 nm respectively) that displayed slower drug release (∼2.5%/day and ∼1%/day respectively). The 20 nm particles exhibited 2- to 5-fold enhanced cell killing potency and 5- to 20-fold increased tumor delivery compared to the larger NPs. The biodistribution of the 20 nm PPT-NPs was highly selective to the tumor with 8-fold higher accumulation than all other examined tissues, while the larger PPT-NPs (30 and 120 nm) exhibited increased liver uptake. Within the tumor, >90% of the 20 nm PPT-NPs penetrated to the hypovascular core, while the larger particles were largely restricted in the hypervascular periphery. The 20 nm PPT-NPs displayed significantly improved efficacy against MDR tumors in mice compared to the larger PPT-NPs, native PPT and the standard taxane chemotherapies, with minimal toxicity.     

Contribution of components of the quadriceps femoris muscle for producing external torque in patients with patellofemoral pain syndrome

IntroductionDifferent muscular activities of the quadriceps components for producing necessary torque may change in patients with patellofemoral pain syndrome (PFPS). The aim of the current study, therefore, was to assess the contribution of each component of the quadriceps femoris muscle for producing external torque in patients with PFPS.MethodTwelve females with PFPS (24.7 ± 2.3 years) and twelve healthy matched females (25.4 ± 2.4 years) performed three consecutive knee flexion and extension movements with maximum effort at 45°/s and 300°/s using a Biodex system 3 dynamometer. Simultaneously, electromyographic (EMG) activities of the vastus medialis oblique (VMO), RF (rectus femoris) and vastus lateralis (VL) muscles were recorded using a DataLog instrument. Standard multiple regressions were used to assess the ability of EMG activities of the VMO, RF and VL muscles to predict normalized quadriceps femoris isokinetic concentric and eccentric torques at 45°/s and 300°/s in the normal and patient groups.ResultsIn the normal group, the VL and the VMO were the good predictors of quadriceps concentric torque at 45°/s and 300°/s, respectively. The VL and the RF were the good predictors of quadriceps eccentric torque at 300°/s in the patient group. No other conditions showed a considerable prediction for quadriceps torque in the normal or patient group.ConclusionFemales with PFPS differ with normal females in terms of the contribution of each component of the quadriceps femoris for producing external torque. Training the VMO for concentric contraction at both high and low velocities should be included in the management of the patients with PFPS.     

Impact of Hepatitis B virus infection on postoperative complications and length of stay in elderly patients with hip fracture: A retrospective cohort study

BackgroundOsteoporosis and subsequent fractures are common in the chronic hepatitis B (CHB) population, especially in the elderly. This study investigated the effects of hepatitis B virus (HBV) infection on postoperative outcomes following hip fracture surgery.MethodsThe study identified elderly patients who underwent hip fracture surgery at three academic tertiary care centres between January 2014 and December 2020. Propensity score matching was performed to compare the outcomes of 1,046 patients with HBV infection to 1,046 controls.ResultsThe seroprevalence of HBV among elderly patients undergoing hip surgery was 4.94%. The HBV cohort had significantly higher rates of medical complications (28.1 vs. 22.7%, p = 0.005), surgical complications (14.0 vs. 9.7%, p = 0.003), and unplanned readmissions (18.9 vs. 14.5%, p = 0.03) within 90 days of surgery. Patients with HBV infection were more likely to have increased length of stay (6.2 vs. 5.9 days, p = 0.009) and in-hospital charges (¥52,231 vs. ¥49,832, p < 0.00001). Multivariate logistic regression suggested that liver fibrosis and thrombocytopenia were independent risk factors for major complications and extended LOS.ConclusionPatients with HBV infection were at greater risk of adverse postoperative outcomes. We should pay more attention to the considerable burden of perioperative management of CHB patients. Due to the high proportion of undiagnosed patients in the Chinese elderly population, universal HBV screening should be considered preoperatively.     

18氟-氟化脱氧葡萄糖在下咽部肿瘤诊断中的作用

目的：研究^18氟—氟化脱氧葡萄糖(^18F-FDG)在下咽部肿瘤诊断中的作用。方法：20例下咽部肿瘤患者均接受^18F-FDG检查及CT、全组内镜(食管、咽喉、气管镜)检查。结果：20例下咽部肿瘤患者^18F-FDG检查结果显示：2例阴性；18例肿瘤原发部位有同位素浓集，其中5例伴异位同位素浓集。对此5例患者进一步临床、病理检查证实：1例食管部占位，2例肺部病变，2例为良性改变。^18F-FDG检查结果显示的病变范围与CT、内镜检查相符。结论：^18F-FDG检查可以提高下咽部肿瘤、尤其是隐匿的并发肿瘤诊断的准确性，明确病变范围，为临床治疗提供依据；同时又是一个简单、易行的下咽部肿瘤的随访检查手段。