Do elderly patients (≥ 75 years old) with glioblastoma benefit from more radical surgeries in the era of temozolomide?

This study assesses the effect of extent of resection (EOR) on the longer-term survival and early mortality of elderly patients (≥ 75 years old) with glioblastoma. We used the Surveillance, Epidemiology, and End Results (SEER) database and data from our center to evaluate the effect of EOR on the long-term survival and early mortality of patients with glioblastoma. We included 50 elderly patients (≥ 75 years old) with glioblastoma visiting our hospital. The median overall survival of the patients who underwent a gross total resection, a subtotal resection, and a partial resection were 278, 200, and 83 days, respectively. The multivariate analysis showed that gross total resection (HR: 0.100; 95% CI: 0.015-0.671, p < 0.001) and subtotal reresection (HR: 0.134, 95% CI: 0.022-0.831, p < 0.001) were independent predictors of favorable prognosis when compared with partial resection. The data extracted from the SEER database also indicated that EOR was an independent predictor of OS, CCS, and early mortality. The stratification analysis revealed that gross total resection was the best protective factor of OS, early mortality, and CCS. Radical resection may improve the OS and CCS of glioblastoma patients aged ≥ 75 years and decrease early mortality.

Association of Chronic Liver Disease and Mortality in Patients With Aneurysmal Subarachnoid Hemorrhage.

Background and Purpose: Chronic liver disease (CLD) is a risk factor for increased morbidity and mortality in acutely ill patients. For patients with aneurysmal subarachnoid hemorrhage (aSAH), the association between CLD and mortality remains unknown. Methods: In this retrospective cohort study, we analyzed consecutive aSAH patients admitted to the West China Hospital between 2009 and 2019. The primary outcome was in-hospital all-cause mortality. Results: This study included 6228 cases of aSAH, 489 (7.9%) of whom also had CLD. In a propensity-matched analysis, CLD was associated with increased mortality in patients with aSAH compared with non-CLD (odds ratio, 2.04 [95% CI, 1.43­2.92]). In aSAH patients with CLD, a high Model for End-Stage Liver Disease score was still associated with an increased odds of mortality. Conclusions: Among aSAH patients, CLD was associated with increased mortality compared with non-CLD. Among aSAH patients with CLD, a higher Model for End-Stage Liver Disease score was associated with an increased odds of mortality.

Neutrophil Counts as Promising Marker for Predicting In-Hospital Mortality in Aneurysmal Subarachnoid Hemorrhage.

Background and Purpose: Systemic inflammation is recognized as a hallmark of stroke. We aimed to evaluate the prognostic value of various inflammatory factors using blood at admission in patients with aneurysmal subarachnoid hemorrhage. Methods: In a multicenter observational study of patients with aneurysmal subarachnoid hemorrhage, the counts of neutrophil, platelet, and lymphocyte were collected on admission. Patients were stratified based on neutrophil counts with propensity score matching to minimize confounding. We calculated the adjusted odds ratios with 95% CIs for the primary outcome of in-hospital mortality and hospital-acquired infections. Results: A total of 6041 patients were included in this study and 344(5.7%) of them died in hospital. Propensity score matching analyses indicated that compared with the lower neutrophil counts, higher neutrophil counts were associated with increased risk of in-hospital mortality (odds ratio, 1.53 [95% CI, 1.14­2.06]), hospital-acquired infections (odds ratio, 1.61 [95% CI, 1.38­1.79]), and delayed neurological ischemic deficits (odds ratio, 1.52 [95% CI, 1.09­1.97]). Moreover, out of all the inflammatory factors studied, neutrophil counts demonstrated the highest correlation with in-hospital mortality and hospital-acquired infections. Conclusions: Among patients with aneurysmal subarachnoid hemorrhage, high neutrophil counts at admission were associated with increased mortality and hospital-acquired infections. The neutrophil count is a simple, useful marker with prognostic value in patients with aneurysmal subarachnoid hemorrhage.

Targeting Frizzled-7 Decreases Stemness and Chemotherapeutic Resistance in Gastric Cancer Cells by Suppressing Myc Expression.

BACKGROUND Although the promoting roles of Frizzled-7 (Fzd7) have been shown before, its effects in gastric cancer (GC) cell stemness are still unclear. The present study assessed the effects of Fzd7 on GC cell stemness and chemoresistance. MATERIAL AND METHODS Clinical samples were used to detect Fzd7 expression and online datasets were used to analyze the correlation between Fzd7 expression and GC patient prognosis. Quantitative real-time PCR (qPCR), Western blot, and spheroid formation were used to detect the stemness of cells and Fzd7-mediated effects on GC cell stemness. Cell viability was assessed to evaluate the role of Fzd7 in chemoresistance of GC cells. RESULTS We found that the expression of Frizzled-7 (Fzd7), a Wnt receptor, was increased in gastric cancer (GC) cells and tissues. Additionally, Fzd7 expression was correlated with shorter overall survival of GC patients. Knockdown of Fzd7 or using inhibitors of Wnt/Fzd (OMP-18R5/Vantictumad) decreased GC cell stemness, characterized as a decrease of spheroid formation ability and expression of stemness regulators. Notably, Fzd7 knockdown or inhibitors of Wnt/Fzd attenuated the chemoresistance of GC cells. Furthermore, elevation of Myc expression rescued the effects of Fzd7 inhibition on GC cell stemness and chemoresistance. CONCLUSIONS Our results suggest that inhibition of Fzd7 decreases the stemness and chemotherapeutic resistance of GC cells.

[Exploration and consideration on establishing a core outcome set of Traditional Chinese Medicine clinical trials in distal radius fracture].

There are inconsistencies in treatment outcomes, measurement instruments, and criteria for assessing clinical effectiveness in studies related to distal radius fractures (DRF), resulting in potential biases and failing to provide high-quality clinical evidence. To address these challenges, international researchers have reached a consensus on developing the core outcome indicator set for distal radius fractures(COS-DRF). However, it's important to note that the existing COS-DRF framework could not reflect the unique characteristics of Traditional Chinese Medicine (TCM) treatment. Currently, there are no established standards for treatment outcomes and measurement instruments specific to TCM clinical research, nor has a COS-DRF been established for TCM clinical studies in China. In light of these gaps, our research team aims to construct a core set of treatment outcomes for TCM clinical research on distal radius fractures. This involves compiling a comprehensive list of treatment outcomes and measurement instruments, initially derived from a thorough literature review and expert consensus, which will then undergo further refinement and updates based on real-world clinical experiences, incorporating feedback from 2 to 3 rounds of expert consensus or Delphi questionnaire surveys. Our goal is to establish a COS-DRF or CMS-DRF that aligns with the principles and practices of TCM, and provide high-quality evidence for clinical practice.

Sensitizing chemotherapy for glioma with fisetin mediated by a microenvironment-responsive nano-drug delivery system.

Drug resistance has become an obstacle to successful cancer chemotherapies, with therapeutic agents effectively traversing the blood-brain barrier (BBB) remaining a great challenge. A microenvironment responsive and active targeting nanoparticle was constructed to enhance the penetration of drugs, leading to improved therapeutic effects. Dynamic light scattering demonstrated that the prepared nanoparticle had a uniform size. The cRGD modification renders the nanoparticle with active targeting capabilities to traverse the BBB for chemotherapy. The disulfide-bond-containing nanoparticle can be disintegrated in response to a high concentration of endogenous glutathione (GSH) within the tumor microenvironment (TME) for tumor-specific drug release, resulting in more effective accumulation. Notably, the released fisetin further increased the uptake of doxorubicin by glioma cells and exerted synergistic effects to promote apoptosis, induce cellular G2/M cycle arrest, and inhibit cell proliferation and migration in vitro. Moreover, the nanoparticle showed favorable anti-glioma effects in vivo. Our study provides a new strategy to overcome drug resistance by utilizing a natural product to sensitize conventional chemotherapeutics with well-designed targeted nanodelivery systems for cancer treatment.

[A retrospective study on manual reduction combined with Chinese Orthopaedic ankle external fixator in the treatment of trimalleolar fracture].

OBJECTIVE: To evaluate the needle puncture safety and clinical efficacy of manual reduction combined with external fixation of ankle frame in the treatment of trimalleolar fracture under the guidance of Chinese Osteosynthesis (CO) theory. METHODS: The clinical data of 118 patients with trimalleolar fractures admitted from December 2010 to December 2021 were retrospectively analyzed. Fifty-three patients were treated with manual reduction combined with external fixation of ankle frame(observation group). Sixty-five patients were treated with open reduction and internal fixation with plate and screws(control group). The operation time, hospitalization days, non-weight-bearing time of the affected limb, clinical healing time of fracture, incidence of complications, visual analogue scale (VAS) before and 1 month after operation, and American Orthopedic Foot and Ankle Society(AOFAS) score of ankle joint before and 1 year after operation were compared between the two groups. RESULTS: Patients in both groups were followed up for more than 1 year. All patients were followed up, and the duration ranged from 14 to 70 months, with an average of(35.28±14.66) months. There were statistically significant in operation time, hospitalization days, non-load-bearing time of affected limbs, clinical healing time of fractures and VAS score one month after operation between the two groups. One month after operation, the VAS score of the observation group was lower than that of the control group(t=3.343, P=0.001). The operation time of the observation group was significantly shorter than that of the control group(t=9.091, P=0.000). The hospitalization days in the observation group were significantly less than those in the control group(t=5.034, P=0.000). The non-load-bearing time of the affected limb in the observation group was significantly shorter than that in the control group(t=11.960, P=0.000). The clinical healing time of fracture in the observation group was significantly shorter than that in the control group(t=4.007, P=0.000). There was no significant difference in AOFAS score between the two groups one year after operation(t=0.417, P=0.678). In the observation group, there were 2 cases of pinhole infection and 3 cases of loss of reduction less than 2 mm. There were 3 cases of surgical incision infection in the control group. There was no significant difference in the incidence of complications between the two groups(χ2=0.446, P=0.504). CONCLUSION: Manual reduction combined with external fixation is safe and effective in the treatment of trimalleolar fracture under the guidance of CO theory, and the function of ankle joint recovers well after operation. This therapy has good clinical value.

[Comparison of clinical efficacy between closed reduction combined with semi-circular external fixator and minimally invasive percutaneous plate osteosynthesis (MIPPO) in the treatment of middle and distal tibia fractures].

OBJECTIVE: To compare the clinical efficacy between closed reduction combined with semi-circular external fixator and minimally invasive percutaneous plate osteosynthesis (MIPPO) in the treatment of middle anddistal tibia fractures. METHODS: The clinical data of sixty patients with middle and distal tibia fractures admitted between January 2019 and November 2022, were retrospectively analyzed. These patients were categorized into external fixation group (n=30) and internal fixation group (n=30). There were 18 males and 12 females in the external fixation group, with an average age of (49.29±2.35) years old. Among them, 14 patients presented with fractures on the left side, and 16 patients presented with fractures on the right side. Closed reduction, arched wire, and semi-circular external fixator were used for treatment. There were 20 males and 10 females in the internal fixation group, with an average age of (48.96±1.87) years old. Among them, 15 patients presented with fractures on the left side, and 15 patients presented with fractures on the right side. MIPPO technique was used for the treatment. Perioperative parameters, including time injury to surgery, surgical duration, incision length, intraoperative bleeding, time to active activity, and incision healing level, were compared between the two groups. Clinical outcomes were also assessed, including Johner-Wruhs scores, time to minimum pain-adapted full weight-bearing, visual analog scale (VAS), SF-36 scale, and complications. RESULTS: The external fixation group exhibited a significantly shorter incision length (1.36±0.86) cm and lower intraoperative bleeding (10.83±5.73) ml compared to the internal fixation group (12.74±3.12) cm and (86.47±8.90) ml, respectively(P<0.05). The postoperative active activity time (1.50±0.54) days and minimum pain-adapted full weight-bearing activity time(108.87±3.43) days in the external fixation group were slightly delayed than the internal fixation group(1.15±0.98) days and (105.27±3.68) days, respectively(P<0.05). Over a mean postoperative follow-up duration of (6.23±1.89) months, both groups showed improved VAS and SF-36 scale scores. There were no statistically significant differences in VAS and SF-36 scale scores 1, 3, 6 months post-operatively between the two groups(P>0.05). The intraoperative surgical time in the external fixation group (35.42±9.31) minutes was shorter than that in the internal fixation group(74.22±7.81) minutes (P<0.05). There was no intraoperative vascular or nerve injury, nor postoperative skin necrosis in the external fixation group. However, skin necrosis was observed in 6 patientsin the internal fixation group, representing a statistically significant difference (P<0.05). CONCLUSION: Both external fixation and plate internal fixation are effective methods for the treatment of middle and distal tibia fractures. External fixation exhibits the advantage of less surgical trauma and a lower incidence of complications.

Brd4 proteolysis-targeting chimera nanoparticles sensitized colorectal cancer chemotherapy.

Bromodomain-Containing Protein 4 (BRD4) is a member of the BET family of bromodomains, which participates in gene transcription process and is closely related to tumor progression. We observed the up-regulated expression of BRD4 in colorectal cancer (CRC) after doxorubicin (DOX) treatment, which might be a potential mechanism for DOX resistance. This study constructed the tumor-targeting (cyclo (Arg-Gly-Asp-D-Phe-Lys)-poly(ethylene glycol)-poly(ε-caprolactone)) (cRGD-PEG-PCL) copolymer for co-delivery of DOX and BRD4 PROTAC degrader ARV-825 (ARV-DOX/cRGD-P) for CRC treatment. The ARV-DOX/cRGD-P complexes elicited synergistic anti-tumor effect via cell cycle arrest and the increased cell apoptosis, and mechanism studies implicated the regulation of proliferation- and apoptosis-related pathways in vitro. Moreover, the administration of ARV-DOX/cRGD-P significantly improved anti-tumor activity in subcutaneous colorectal tumors and colorectal intraperitoneal disseminated tumor models in mice by promoting tumor apoptosis, suppressing tumor proliferation and angiogenesis. Taken together, these data reveal that ARV-825 can heighten DOX sensitivity in CRC treatment and BRD4 is a potential therapeutic target for DOX-resistant CRC. The ARV-DOX/cRGD-P preparations have outstanding anti-cancer effects and may be used for clinical treatment of colorectal cancer in the future.

A BRD4 PROTAC nanodrug for glioma therapy via the intervention of tumor cells proliferation, apoptosis and M2 macrophages polarization.

Glioma is a primary aggressive brain tumor with high recurrence rate. The poor efficiency of chemotherapeutic drugs crossing the blood‒brain barrier (BBB) is well-known as one of the main challenges for anti-glioma therapy. Moreover, massive infiltrated tumor-associated macrophages (TAMs) in glioma further thwart the drug efficacy. Herein, a therapeutic nanosystem (SPP-ARV-825) is constructed by incorporating the BRD4-degrading proteolytic targeting chimera (PROTAC) ARV-825 into the complex micelle (SPP) composed of substance P (SP) peptide-modified poly(ethylene glycol)-poly(d,l-lactic acid)(SP-PEG-PDLLA) and methoxy poly(ethylene glycol)-poly(d,l-lactic acid) (mPEG-PDLLA, PP), which could penetrate BBB and target brain tumor. Subsequently, released drug engenders antitumor effect via attenuating cells proliferation, inducing cells apoptosis and suppressing M2 macrophages polarization through the inhibition of IRF4 promoter transcription and phosphorylation of STAT6, STAT3 and AKT. Taken together, our work demonstrates the versatile role and therapeutic efficacy of SPP-ARV-825 micelle against glioma, which may provide a novel strategy for glioma therapy in future.

Association between hospital characteristics and 30-day mortality of patients hospitalized for acute myocardial infarction in Sichuan, China.

OBJECTIVE: Because acute myocardial infarction (AMI) is a major cause of death, China faces the challenge of improving its quality of care. This study provides context-specific evidence of association between 30-day mortality and hospital characteristics in China to extend the understanding of hospitalized AMI patients. METHODS: We conducted a retrospective cohort study of 67,619 hospitalized AMI patients at 372 tertiary and secondary hospitals in Sichuan, China, between January 1, 2018 and December 31, 2020. Using a hierarchical logistic regression model to control risk factors, we explored relationships among 30-day mortality, hospital level, AMI volume, and percutaneous coronary intervention (PCI) timeliness. Locally weighted scatterplot smoothing was used to observe the trends of 30-day mortality with increased AMI volume and PCI timeliness. RESULTS: After risk factor adjustment, the 30-day mortality model demonstrated that a lower hospital level and smaller AMI volume were associated with higher 30-day mortality (medium-volume: OR = 1.511, 95% CI (1.195, 1.910); small-volume: OR = 1.636, 95% CI (1.277, 2.096); other tertiary: OR = 1.190, 95% CI (1.037, 1.365); secondary: OR = 1.524, 95% CI (1.289, 1.800)). Similarly, 30-day mortality was higher for patients at hospitals with a low PCI timeliness (low timeliness: OR = 1.318, 95% CI (1.079, 1.610)). Scatterplot smoothing showed hospital 30-day mortality first reduced quickly and gradually stabilized with increased AMI volume and PCI timeliness. CONCLUSION: Patients admitted to tertiary grade A hospitals, large-volume hospitals, and high- or medium-timeliness hospitals were more likely to survive at 30 days. Policymakers should focus on improving the outcomes at hospitals without these characteristics.

Enhanced anti-glioma efficacy of doxorubicin with BRD4 PROTAC degrader using targeted nanoparticles.

Current treatment of glioma is hampered due to the physical blood-brain barrier (BBB) and the resistance to traditional chemotherapeutic agents. Herein, we proposed a combined treatment strategy based on Cyclo (Arg-Gly-Asp-d-Phe-Lys) (cRGDfk) peptides-modified nanoparticle named cRGD-P in a self-assembly method for the co-delivery of doxorubicin (DOX) and BRD4 PROTAC degrader ARV-825 (ARV). Molecular dynamics simulations showed that cRGD-P could change its conformation to provide interaction sites for perfectly co-loading DOX and ARV. The cRGD-P/ARV-DOX exhibited an average size of 39.95 â€‹nm and a zeta potential of -0.25 â€‹mV. Increased expression of BRD4 in glioma cells was observed after being stimulated by cRGD-P/DOX, confirming one of the possible mechanisms of DOX resistance and the synergistic tumor inhibition effect of BRD4 degrading ARV combined with DOX. In the study, the combination of DOX and ARV in the cRGD-P nanoparticle system exhibited synergistic suppression of tumor growth in glioma cells on account of cell cycle arrest in the G2/M phase and the activation of tumor cells apoptosis-related pathways including triggering caspase cascade and downregulating Bcl-2 as well as upregulating Bax. The cRGD-P/ARV-DOX system could effectively suppress the heterotopic and orthotopic growth of glioma by increasing tumor apoptosis, inhibiting tumor proliferation, and decreasing tumor angiogenesis in vivo. Therefore, the cRGD-modified nanoparticle to co-deliver DOX and ARV provides a potential platform for exploiting a more effective and safer combination therapy for glioma.

Effects and Anti-rotation Stabilization of the Non-bridging External Fixation for Pronation-Abduction Stage III Ankle Fracture: A Cadaveric Study.

OBJECTIVE: This study is aimed at providing a nonbridging external fixation technique with pinning fixation for the pronation-abduction stage III ankle fracture. The secondary purpose was to evaluate its effect on anatomic reduction and fracture fragment stability against cadaveric models' rotation. METHOD: A paired design study was conducted using 14 pairs of the cadaveric model which had been modeled for pronation-abduction stage III ankle fracture. One fracture model from each pair was randomly allocated to receive an open reduction and internal fixation, while the other was reduced and stabilized with the external fixation technique. After the surgery, the antirotational stability tests were performed with external rotation torques of 10 nm, 15 nm, and 20 nm applied, respectively. The postoperation reduction rate and ankle parameters were recorded in anteroposterior and lateral radiographs before and after the antirotational stability experiment. RESULT: The outcomes were assessed according to Burwell-Charnley's radiographic criteria of reduction. It showed no statistically significant differences in reduction between the two groups (P < 0.05). The displacement of lateral fragment following a reduction in the external fixation group was significantly larger than that of the internal fixation group (3.14 ± 0.56 vs. 1.49 ± 0.39, P < 0.05). After applying rotational torques of 10 nm, 15 nm, and 20 nm, the results of other parameters showed no significant differences between the two groups. CONCLUSION: This nonbridging external fixation method with pin fixation of fracture fragments might have the same effect as that of internal fixation on the reduction rate of pronation-abduction stage III ankle fracture.

Comparison of complications of early and delayed open reduction and internal fixation for treating pilon fracture: A protocol of systematic review and meta-analysis.

BACKGROUND: Tibial Pilon fractures are severe fractures accompanied by soft tissue injury. Although open reduction and internal fixation (ORIF) are effective in treating Pilon fractures, there is a controversy over time to surgery due to reported postoperative complications. However, there is no systematic review evaluating the difference of postoperative complications between early and delayed ORIF for treating pilon fractures. METHODS: Relevant literature written in English will be searched through PubMed, Cochrane Library, Embase, MEDLINE, and Web of Science. The study aims to compare the effects and complications of early and delayed ORIF for treating fresh pilon fractures in adult patients. The primary outcome will be infection rate, fracture union time, nonunion and malunion rate. And the secondary outcome will be metalwork removal, amputation, and ankle function grade. Two reviewers will independently assess the eligibility of the studies according to the pre-defined inclusion and exclusion criteria. A meta-analysis for the available data will be conducted using Revman 5.3. To measure effect size, odds ratios (ORs) and mean difference will be used for dichotomous and continuous data, respectively. Statistical heterogeneity will be explored. And a random-effects model or a fixed-effects will be used in pooled data on the basis of the existence or absence of heterogeneity. Subgroup analysis will be conducted to identify sources of heterogeneity and sensitivity analysis to test the results' robustness. We will assess the risk of bias by four different quality assessment tools according to the study design. Publication bias will be evaluated by funnel plot. The study data will be stored in the Open Science Framework website. PROSPERO REGISTRATION NUMBER: CRD42020207465.

[Finite element analysis on stress concentration improvement in patellofemoral joint by releasing lateral patellar retinaculum with stiletto needle based on the theory of Jinshugu()].

OBJECTIVE: To study mechanism of improvement of stress concentration on patellofemoral joint by stiletto needle releasing lateral patellar retinaculum guided by the theory of Jinshugu() and based on the finite element model of knee joint. and to elucidate the biomechanical mechanism of stiletto needle releasing changing patellar trajectory and reducing patellofemoral joint pressure. METHODS: CT data of knee joint from a normal male (aged 29, heighted 171 cm, weighted 58 kg) was selected. Starting with construction of three-dimensional model of knee joint by using finite element software, the finite element model of knee joint with complete tendonand bone structures were established through several steps, such as geometric reconstruction, reverse engineering, meshing, material assignment and loading analysis. The loading condition was set as 500 N load on knee joint, and the average tensile stress of quadriceps femoris tendon was about 200 N. To simulate the release of lateral patellar retinaculum by stiletto needle at 30 and 90 position of knee flexion in finite element model separately, and to compare the improvement of stress concentration of patellofemoral joint by stiletto needle intervention under different knee flexion conditions. RESULTS: The peak stress of patellofemoral joint and tibiofemoral joint decreased after stiletto needle releasing of patellofemoral lateral retinaculum compared with before intervention, which was(1) knee flexion at 30 degrees:patellar cartilage decreased by 0.498 MPa (decreased 9.06%), femoral trochlea decreased by 0.886 MPa(decreased 16.27%);(2) knee flexion at 90 degrees:patellar cartilage decreased by 0.558 MPa (decreased 8.6%), femoral trochlea decreasedby 0.607 MPa (decreased 9.94%). CONCLUSION: Releasing lateral patellofemoral retinaculum with stiletto needle could effectively alleviate the stress concentration of patellofemoral joint and reduce local stress peak value, which it is helpful to improve patellar trajectory and make stress distribution more uniform.

Tumor Targeted Curcumin Delivery by Folate-Modified MPEG-PCL Self-Assembly Micelles for Colorectal Cancer Therapy.

INTRODUCTION: Curcumin (Cur) is a natural extract of Asian spice Curcumin longa, showing multi-targeting capability and low toxicity in anti-tumor activities. The low bioavailability restricts its application as a therapeutic agent. Folate (FA) receptors are highly expressed in many malignant tumors while low expressed in normal tissue. Herein, we developed a self-assembled FA modified MPEG-PCL micelle to incorporate Cur (FA/Nano-Cur) and applied it for colorectal cancer therapy. METHODS: We prepared FA/Nano-Cur micelles and identified their characteristics. The drug release behavior, pharmacokinetics and in vitro anti-tumor activities of FA/Nano-Cur were studied. Furthermore, the in vivo anti-tumor ability assessment and anti-tumor mechanisms investigation were carried out in murine colorectal cancer model. RESULTS: FA/Nano-Cur micelles had an average particle size of 30.47 nm. Elongated T1/2 and larger AUC were found in FA/Nano-Cur group than that in the Free Cur group. MTT assay and apoptotic study indicated the growth inhibitory effect and pro-apoptotic effect of FA/Nano-Cur were the most significant among all treatments. Moreover, the in vivo study demonstrated that FA/Nano-Cur micelles exhibited a much stronger effect to suppress tumor growth, promote tumor apoptosis and attenuate tumor angiogenesis than Free Cur and Nano-Cur micelles. CONCLUSION: The present study demonstrated FA/Nano-Cur micelles might be a promising therapeutic agent in colorectal cancer treatment with distinctive advantages of improved bioavailability, sustained drug release, tumor-targeted delivery and low toxicity.

Thermosensitive In Situ Gel Containing Luteolin Micelles is a Promising Efficient Agent for Colorectal Cancer Peritoneal Metastasis Treatment.

Luteolin (Lut) is a natural flavonoid mainly extracted from vegetables and fruits. Lut shows great anti-tumor potential in many malignant cancers, which are hindered by poor water solubility and low bioavailability. Peritoneal metastasis is a challenge for colorectal cancer treatment, usually indicating unfavorable prognosis of patients. Methoxy poly(ethylene glycol)-poly(ε-caprolactone) micelles containing Luteolin (Lut-M) and thermosensitive Pluronic®F127 coated Lut-M (Lut-M-F127) were synthesized and applied in the local therapy of colorectal cancer. Drug release study of Lut-M-F127 and Lut-M suggested extended drug release, and the release of Lut from Lut-M-F127 was slower than Lut-M. It was also proved that Lut-M-F127 could transit from solution to gel at body temperature. Moreover, both Lut-Free and Lut-M micelles were capable of inducing tumor cell apoptosis and reducing cell viability in vitro. Our results further demonstrated the therapeutic effect of Lut-M-F127 treatment was much better than that of Lut-M treatment in vivo. Lut-M-F127 has shown strong ability to promote tumor apoptosis, suppress tumor proliferation and block tumor angiogenesis. In summary, Lut-M-F127 formulation may be a very promising treatment option for peritoneal metastasis in colorectal cancer in the future.

Co-Delivery of Docetaxel and Curcumin via Nanomicelles for Enhancing Anti-Ovarian Cancer Treatment.

INTRODUCTIONS: Ovarian cancer is a stubborn malignancy of gynecological system with a high mortality rate. Docetaxel (DTX), the second-generation of anti-tumor drug Taxane, has shown superior efficacy over classic paclitaxel (PTX) in certain cancers. However, its clinical application is hindered by poor bioavailability. The natural spice extract curcumin (Cur) has been discovered to improve the bioavailability of DTX. Therefore, it is meaningful to develop a combined drug strategy of DTX and Cur with methoxy poly (ethylene glycol)-poly (L-lactic acid) (MPEG-PLA) copolymers in ovarian cancer therapy. METHODS: Injectable DTX-Cur/M nanomicelles were synthesized and characterized in the study. The molecular interactions between DTX, Cur and copolymer were simulated and the drug release behavior was investigated. The anti-tumor activity and anti-tumor mechanisms of DTX-Cur/M were evaluated and explored in both cells and mice model of xenograft human ovarian cancer. RESULTS: DTX-Cur/M nanomicelles with an average particle size of 37.63 nm were obtained. The drug release experiment showed sustained drug release from DTX-Cur/M nanomicelles. The MTT assay and apoptotic study indicated that DTX-Cur/M exhibited stronger inhibition and pro-apoptotic effects on A2780 cells compared with DTX or Cur alone. In vivo anti-tumor experiment results confirmed that the DTX-Cur/M played the most effective role in anti-ovarian cancer therapy by inhibiting tumor proliferation, suppressing tumor angiogenesis and promoting tumor apoptosis. CONCLUSION: We designed injectable DTX-Cur/M nanomicelles for co-delivery of DTX and Cur agents to the tumor site through systemic administration. The DTX-Cur/M nanomicelle would be a biodegradable, sustainable and powerful anti-tumor drug candidate with great potential in ovarian cancer treatment.

[Construction and simulation mechanical analysis of dynamic knee joint finite element model based on CT image].

OBJECTIVE: To construct a dynamic knee joint finite element model based on CT image data and verify the validity of the model. To provide a simulation model and basic data for biomechanical research of the knee joint by further finite element analysis. METHODS: The CT data of a healthy male knee joint was selected. With the help of Mimics 19.0 and Hypermesh 12.0 software, a high simulation finite element model of knee joint was established following steps, including geometric reconstruction, reverse engineering, meshing and material characterization. The dynamic knee flexion model was generated by determining the boundary conditions and torque loading, and the validity of themodel was confirmed. The biomechanical changes of the tibiofemoral and patellofemoral joints under different knee flexion angles were analyzed by applying the loads (500 N) to the finite element model during knee flexion. RESULTS: A finite element model of knee joint was established based on CT images and anatomical characteristics. The model included three-dimensional elements such as bone, ligament, cartilage, meniscus and patellar retinaculum. The different finite element models of knee flexion states were produced by applying different torques after establishing boundary conditions. According to equivalent conditions (knee flexion 30 degrees, quadriceps tendon under 200 N stretch), the peak stress value of patella was 2.209 MPa and the average Mises stress was 1.132 MPa; the peak stress value of femoral trochlear was 1.405 MPa and the average Mises stress was 0.936 MPa. The validity of the model was proved by the difference between the model and previous studies of 1% to 13.5%. Dynamic model loading showed that the Mises stressof tibiofemoral joint decreased with the increase of knee flexion angle, while the Mises stress of patellofemoral joint was positively correlated with knee flexion angle. The Mises stress of cartilage stress planes at different knee flexion angles was significantly different(P<0.05). CONCLUSION: The finite element model established in this study is more comprehensive and can effectively simulate the biomechanical characteristics of dynamic knee joint, which provides support for further simulation mechanics researches of the knee joint.

The effectiveness and safety of plaster splint and splints for distal radius fractures: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: To assess the efficacy and safety of plaster splint vs splints in the treatment of distal radius fractures (DRFs). METHODS: For a more comprehensive collection of original study, we mainly searched 9 electronic databases including the PubMed, Web of Science, EMBASE, Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL), Clinical Trials.gov, the Chinese National Knowledge Infrastructure Database (CNKI), Wanfang Database, and VIP Database. The retrieval date of all databases is from the establishment to January 2019. In the aspect of assessing the quality of original research methodology, we mainly rely on the Cochrane risk bias assessment tool and GRADE assessment method. Revman 5.3 is used for statistical analysis. RESULTS: A total of 8 studies involving 717 participants were included. The results showed that effective rate (RR = 0.99, 95%CI 0.91 to 1.07, P = .83), reduction rate (RR = 1.00, 95%CI 0.93 to 1.07, P = .98), and complication rate of the plaster splint had no significant difference with the splint. In addition, for the excellent rate of treatment, subgroup analysis based on the included studies found that when the intervention period was 4 weeks, the plaster splint was better than the splint, and when the intervention period was more than 4 weeks, there was no significant difference between them. CONCLUSIONS: There is no sufficient evidence that plaster splint is superior to splint. However, according to current evidence, plaster splint is more effective than splint when the intervention period is shorter (4 weeks), and its advantage disappears when the intervention period is longer (> 4 weeks). It should be noted that the results of this study were influenced by the sample size and the quality of the included studies. More high-quality and well-controlled RCTs are needed to draw better conclusions in further study.