Multi-level chemical characterization and anti-inflammatory activity evaluation of the polysaccharides from Prunella vulgaris.

Prunella vulgaris (PV) is a medicine and food homologous plant, but its quality evaluation seldom relies on the polysaccharides (PVPs). In this work, we established the multi-level fingerprinting and in vitro anti-inflammatory evaluation approaches to characterize and compare the polysaccharides of P. vulgaris collected from the major production regions in China. PVPs prepared from 22 batches of samples gave the content variation of 5.76-24.524 mg/g, but displayed high similarity in the molecular weight distribution. Hydrolyzed oligosaccharides with degrees of polymerization 2-14 were characterized with different numbers of pentose and hexose by HILIC-MS. The tested 22 batches of oligosaccharides exhibited visible differences in peak abundance, which failed to corelate to their production regions. All the PVPs contained Gal, Xyl, and Ara, as the main monosaccharides. Eleven batches among the tested PVPs showed the significant inhibitory effects on NO production on LPS-induced RAW264.7 cells at 10 µg/mL, but the exerted efficacy did not exhibit correlation with the production regions. Conclusively, we, for the first time, investigated the chemical features of PVPs at three levels, and assessed the chemical and anti-inflammatory variations among the different regions of P. vulgaris samples.

Impact of optical navigation variables on the accuracy of robot-assisted surgery: a study of the TIANJI Robot system.

This study aims to explore factors related to optical navigation that interfere with the accuracy of robot-assisted surgery, specifically focusing on the TIANJI Robot system. A measurement model was created to assess the accuracy of the TIANJI Robot system in simulated screw placement. Deviation between actual and planned positions was measured using a three-coordinate machine. Various experiments were conducted to investigate the impact of different optical navigation factors on screw placement accuracy. Deviations were measured at different distances (ranging from 1.2 to 2.2 m) between the optical navigation stereo camera and the tracker, with each distance being tested 50 times. The distance between the optical camera and patient tracker was set at 1.4 m. Deviations were also measured at different angles between the camera and robot tracker, repeated over 25 times for each angle. Data were analyzed using mean and standard deviation, with line charts illustrating deviation changes based on distance and angle details. Within the range of the TIANJI Robot system's optical navigation (1.2-2.2 m), deviation increased as distance increased (χ2 = 479.107, P < 0.001). The robotic system demonstrated high and consistent accuracy (mean deviation: 0.332 mm ± 0.067 mm) when the relative angle between the optical camera and tracker was below 40°. The accuracy of the TIANJI Robot system was found to be influenced by relative distance and angle between the optical camera and tracker during screw placement procedures. Surgeons are recommended to set a relative distance of 1.4-1.5 m between the optical camera and patient tracker, with a relative angle below 40° when placing and adjusting optical tracking devices.

Deep learning-based identification of spine growth potential on EOS radiographs.

OBJECTIVES: To develop an automatic computer-based method that can help clinicians in assessing spine growth potential based on EOS radiographs. METHODS: We developed a deep learning-based (DL) algorithm that can mimic the human judgment process to automatically determine spine growth potential and the Risser sign based on full-length spine EOS radiographs. A total of 3383 EOS cases were collected and used for the training and test of the algorithm. Subsequently, the completed DL algorithm underwent clinical validation on an additional 440 cases and was compared to the evaluations of four clinicians. RESULTS: Regarding the Risser sign, the weighted kappa value of our DL algorithm was 0.933, while that of the four clinicians ranged from 0.909 to 0.930. In the assessment of spine growth potential, the kappa value of our DL algorithm was 0.944, while the kappa values of the four clinicians were 0.916, 0.934, 0.911, and 0.920, respectively. Furthermore, our DL algorithm obtained a slightly higher accuracy (0.973) and Youden index (0.952) compared to the best values achieved by the four clinicians. In addition, the speed of our DL algorithm was 15.2 ± 0.3 s/40 cases, much faster than the inference speeds of the clinicians, ranging from 177.2 ± 28.0 s/40 cases to 241.2 ± 64.1 s/40 cases. CONCLUSIONS: Our algorithm demonstrated comparable or even better performance compared to clinicians in assessing spine growth potential. This stable, efficient, and convenient algorithm seems to be a promising approach to assist doctors in clinical practice and deserves further study. CLINICAL RELEVANCE STATEMENT: This method has the ability to quickly ascertain the spine growth potential based on EOS radiographs, and it holds promise to provide assistance to busy doctors in certain clinical scenarios. KEY POINTS: • In the clinic, there is no available computer-based method that can automatically assess spine growth potential. • We developed a deep learning-based method that could automatically ascertain spine growth potential. • Compared with the results of the clinicians, our algorithm got comparable results.

Characterization and comparison of cardiomyocyte protection activities of non-starch polysaccharides from six ginseng root herbal medicines.

Ginseng is rich of polysaccharides, however, the evidence supporting polysaccharides to distinguish various ginseng species is rarely reported. Focusing on six root ginseng (e.g., Panax ginseng-PG, P. quinquefolius-PQ, P. notoginseng-PN, red ginseng-RG, P. japonicus-PJ, and P. japonicus var. major-PJM), the contained non-starch polysaccharides (NPs) were structurally characterized and compared by both the chemical and biological evaluation. Holistic fingerprinting at three levels (the NPs and the acid hydrolysates involving oligosaccharides and monosaccharides) utilized various chromatography methods, and the treatment of H9c2 cells with the NPs by OGD and H2O2-induced injury models was used to assess the protective effect. NPs from six Panax herbal medicines occupied about 20 % of the total polysaccharides, which were of the highest content in RG and the lowest in PN. NPs from six ginseng exhibited weak differentiations in the molecular weight distribution, while marker oligosaccharides were found to distinguish PN and RG from the others. Glc and GalA were more abundant in the NPs for PG and RG, respectively. NPs from PQ (100/200 µg/mL) showed significant cardiomyocyte protection effect by regulating the mitochondrial functions. This work further testifies the role of polysaccharides in quality control of herbal medicine, with new markers discovered beneficial to distinguish the ginseng.

Folic acid conjugated palygorskite/Au hybrid microgels: Temperature, pH and light triple-responsive and its application in drug delivery.

Herein, folic acid conjugated poly (NIPAM-co-functional palygorskite-Au-co-acrylic acid) (FA-PNFA) hybrid microgels were fabricated by emulsion polymerization. The introduction of acrylic acid can increase the low critical solution temperature (LCST) of FA-PNFA from 36 °C at pH 5.5-42 °C at pH 7.4. Doxorubicin hydrochloride (DOX) was chosen as the load drug, the results show that the DOX release behavior is driven by temperature, pH and light. Cumulative drug release rate can reach 74 % at 37 °C and pH 5.5 while only 20 % at 37 °C and pH 7.4, which effectively avoided the early leakage of the drug. In addition, by exposing FA-PNFA hybrid microgels to laser irradiation, the cumulative release rate was increased by 5 % compared to the release rate under dark conditions. Functional palygorskite-Au as physical crosslinkers not only improves the drug loading content of microgels but also promotes the release of DOX through light drive. Methyl thiazolyl tetrazolium bromide (MTT) assay demonstrated that the FA-PNFA are nontoxic up to 200 µg mL-1 towards 4T1 breast cancer cell. Meanwhile, DOX-loaded FA-PNFA show more significant cytotoxicity than the free DOX. Confocal laser scanning microscope (CLSM) revealed that the DOX-loaded FA-PNFA could be efficiently taken by 4T1 breast cancer cells. FA-PNFA hybrid microgels not only improve the LCST of PNIPAM, but also endow the microgels with photostimulation responsiveness, which can release drugs in response to the triple stimulation response of temperature, pH and light, thus effectively reducing the activity of cancer cells, making them more promising for wider medical applications.

Degradation Profiling of Nardosinone at High Temperature and in Simulated Gastric and Intestinal Fluids.

Nardosinone, a predominant bioactive product from Nardostachys jatamansi DC, is well-known for its promising therapeutic applications, such as being used as a drug on anti-inflammatory, antidepressant, cardioprotective, anti-neuroinflammatory, anti-arrhythmic, anti-periodontitis, etc. However, its stability under varying environmental conditions and its degradation products remain unclear. In this study, four main degradation products, including two previously undescribed compounds [2-deoxokanshone M (64.23%) and 2-deoxokanshone L (1.10%)] and two known compounds [desoxo-narchinol A (2.17%) and isonardosinone (3.44%)], were firstly afforded from the refluxed products of nardosinone in boiling water; their structures were identified using an analysis of the extensive NMR and X-ray diffraction data and the simulation and comparison of electronic circular dichroism spectra. Compared with nardosinone, 2-deoxokanshone M exhibited potent vasodilatory activity without any of the significant anti-neuroinflammatory activity that nardosinone contains. Secondly, UPLC-PDA and UHPLC-DAD/Q-TOF MS analyses on the degradation patterns of nardosinone revealed that nardosinone degraded more easily under high temperatures and in simulated gastric fluid compared with the simulated intestinal fluid. A plausible degradation pathway of nardosinone was finally proposed using nardosinonediol as the initial intermediate and involved multiple chemical reactions, including peroxy ring-opening, keto-enol tautomerization, oxidation, isopropyl cleavage, and pinacol rearrangement. Our findings may supply certain guidance and scientific evidence for the quality control and reasonable application of nardosinone-related products.

Accuracies of various types of spinal robot in robot-assisted pedicle screw insertion: a Bayesian network meta-analysis.

BACKGROUND: With the popularization of robot-assisted spinal surgeries, it is still uncertain whether robots with different designs could lead to different results in the accuracy of pedicle screw placement. This study aimed to compare the pedicle screw inserting accuracies among the spinal surgeries assisted by various types of robot and estimate the rank probability of each robot-assisted operative technique involved. METHODS: The electronic literature database of PubMed, Web of Science, EMBASE, CNKI, WANFANG and the Cochrane Library was searched in November 2021. The primary outcome was the Gertzbein-Robbins classification of pedicle screws inserted with various operative techniques. After the data extraction and direct meta-analysis process, a network model was established in the Bayesian framework and further analyses were carried out. RESULTS: Among all the 15 eligible RCTs, 4 types of robot device, namely Orthbot, Renaissance, SpineAssist and TiRobot, were included in this study. In the network meta-analysis, the Orthbot group (RR 0.27, 95% CI 0.13-0.58), the Renaissance group (RR 0.33, 95% CI 0.14-0.86), the SpineAssist group (RR 0.14, 95% CI 0.06-0.34) and the conventional surgery group (RR 0.21, 95% CI 0.13-0.31) were inferior to the TiRobot group in the proportion of grade A pedicle screws. Moreover, the results of rank probabilities revealed that in terms of accuracy, the highest-ranked robot was TiRobot, followed by Renaissance and Orthbot. CONCLUSIONS: In general, current RCT evidence indicates that TiRobot has an advantage in the accuracy of the pedicle screw placement, while there is no significant difference among the Orthbot-assisted technique, the Renaissance-assisted technique, the conventional freehand technique, and the SpineAssist-assisted technique in accuracy.

Ectopic bronchogenic cyst of liver misdiagnosed as gallbladder diverticulum: A case report.

BACKGROUND: Ectopic bronchogenic cysts are a type of congenital cystic tumor that are extremely difficult to diagnose and can be ectopically located in various organs, with the possibility of malignant transformation. Here we report a case of an ectopic bronchogenic cyst in the liver initially misdiagnosed as a gallbladder diverticulum. CASE SUMMARY: The patient was a middle-aged woman whose chief complaint was intermittent pain in the upper abdomen. Imaging examination revealed a cystic space in the left inner lobe of the liver. She was admitted to our hospital for treatment. Based on abdominal examination and imaging findings, the initial diagnosis was gallbladder diverticulum with cholestasis combined with chronic cholecystitis. However, following intraoperative observations and postoperative pathologic assessment, the diagnosis was revised to ectopic bronchogenic cyst of the liver. CONCLUSION: Radiologists, hepatobiliary and pancreatic surgeons, gastrointestinal surgeons, urologists, and even neurosurgeons should be aware and consider a possible diagnosis of ectopic bronchogenic cysts, especially when other types of cyst, cystadenoma, and other diseases are excluded. The disease and its complications should be detected and correctly diagnosed and treated as early as possible in order to avoid adverse outcomes.

Longitudinal Spinous-Splitting Laminoplasty with Coral Bone for the Treatment of Cervical Adjacent Segment Degenerative Disease: A 5-Year Follow-up Study.

This study was designed to analyze the causes of cervical adjacent segment degenerative disease (ASDis), evaluate the surgical outcomes of longitudinal spinous-splitting laminoplasty with coral bone (SLAC) during cervical reoperation, and accumulate data on reoperation with SLAC in a primary hospital. Based on the inclusion and exclusion criteria, we conducted a retrospective study involving 52 patients who underwent cervical reoperation for ASDis using SLAC at the spinal surgery department of the Beijing Jishuitan Hospital from 1998 to 2014. Among them, 39 were treated with anterior cervical fusion and internal fixation during the first operation (anterior cervical corpectomy with fusion [ACCF], n = 24; anterior cervical discectomy and fusion [ACDF], n = 11; and cervical disc arthroplasty [CDA], n = 4). Outcomes were the Japanese Orthopaedic Association (JOA) score, neck disability index (NDI) score, upper limb/neck and shoulder evaluated using a visual analogue scale (VAS), and rates of ASDis. In patients who underwent an anterior cervical approach in the first instance, the incidence of ASDis was significantly higher in the C3/4 gap than in the other gaps. In the ACCF group, the lateral radiograph of the cervical spine revealed that the distance between the anterior cervical plate and the adjacent segment disc was <5 mm in 15 (62.5%) cases and five (12.8%) cases, respectively, the internal fixation screws broke into the annulus of the adjacent segment. After the first SLAC, ASDis developed at C2/3 and C3/4 in four (30.8%) and eight (61.5%) cases, respectively. After reoperation, all cases were followed up for >5 (average, 6.2) years. The pre-reoperation and last follow-up values were as follows: mean Japanese Orthopaedic Association score, 10.2 ± 1.5 vs 15.5 ± 0.7 (P = 0.03); neck disability index, 26.2 vs 13.6 points (P = 0.01); upper-limb visual analog scale (VAS) score, 6.1 vs 2.6 points (P = 0.04); and neck and shoulder VAS score, 6.6 vs 2.1 points (P = 0.03). SLAC is a simple technique in which the local anatomy is clearly visible and satisfactory clinical outcomes are obtained.

Mitochondrial proteome of mouse oocytes and cisplatin-induced shifts in protein profile.

Mitochondria are essential organelles that provide energy for mammalian cells and participate in multiple functions, such as signal transduction, cellular differentiation, and regulation of apoptosis. Compared with the mitochondria in somatic cells, oocyte mitochondria have an additional level of importance since they are required for germ cell maturation, dysfunction in which can lead to severe inherited disorders. Thus, a systematic proteomic profile of oocyte mitochondria is urgently needed to support the basic and clinical research, but the acquisition of such a profile has been hindered by the rarity of oocyte samples and technical challenges associated with capturing mitochondrial proteins from live oocytes. Here, in this work, using proximity labeling proteomics, we established a mitochondria-specific ascorbate peroxidase (APEX2) reaction in live GV-stage mouse oocytes and identified a total of 158 proteins in oocyte mitochondria. This proteome includes intrinsic mitochondrial structural and functional components involved in processes associated with "cellular respiration", "ATP metabolism", "mitochondrial transport", etc. In addition, mitochondrial proteome capture after oocyte exposure to the antitumor chemotherapeutic cisplatin revealed differential changes in the abundance of several oocyte-specific mitochondrial proteins. Our study provides the first description of a mammalian oocyte mitochondrial proteome of which we are aware, and further illustrates the dynamic shifts in protein abundance associated with chemotherapeutic agents.

Characterization of Machined Surface Topography Based on the Normal Declination Angle of Microfacets.

It is important to characterize surface topography in order to study machined surface characteristics. Due to the features of periodicity and randomness of machined surface topography, the existing topographical parameters may not describe its features accurately. A novel characterization method called the normal declination angle of microfacet-based surface topography is thus proposed for this task. The topography of machined surfaces is measured and the data on the normal declination angle are obtained. Then, surface topography is analyzed via the distribution of the normal declination angle. The lognormal distribution characterization model of machined surface topography is established, and the accuracy of the model is verified by error analysis. The results show that the calculated results of the present characterization model are generally consistent with the distribution of the normal declination angle, where the maximal root mean square errors (RMSE) is 4.5%. Therefore, this study may serve as an effective and novel way to describe the characteristics of the machined surface topography.

Improvement of Oral Bioavailability and Anti-Tumor Effect of Zingerone Self-Microemulsion Drug Delivery System.

This study sought to prepare a self-microemulsion drug delivery system containing zingerone (Z-SMEDDS) to improve the low oral bioavailability of zingerone and anti-tumor effect. Z-SMEDDS was characterized by particle size, zeta potential and encapsulation efficiency, while its pharmacokinetics and anti-tumor effects were also evaluated. Z-SMEDDS had stable physicochemical properties, including average particle size of 17.29 ± 0.07 nm, the zeta potential of -22.81 ± 0.29 mV, and the encapsulation efficiency of 97.96% ± 0.02%. In vitro release studies have shown the release of zingerone released by Z-SMEDDS was significantly higher than free zingerone in different release media. The relative oral bioavailability of Z-SMEDDS was 7.63 times compared with free drug. Meanwhile, the half inhibitory concentration （IC50）of Z-SMEDDS and free zingerone was 8.45 µg/mL and 13.30 µg/mL, respectively on HepG2. This study may provide a preliminary basis for further clinical research and application of Z-SMEDDS.

TCR-Induced Tyrosine Phosphorylation at Tyr270 of SUMO Protease SENP1 by Lck Modulates SENP1 Enzyme Activity and Specificity.

Small ubiquitin-like modifier (SUMO) modification plays an important regulatory role in T cell receptor (TCR) signaling transduction. SUMO-specific proteases (SENPs) have dual-enzyme activities; they can both process SUMO precursors as endopeptidases and participate in SUMO deconjugation as isopeptidases. It remains unclear how the SUMO system, especially SENP1, is regulated by TCR signaling. Here, we show that Lck phosphorylates tyrosine 270 (Y270) of SENP1 upon TCR stimulation, indicating that SENP1 is a substrate of Lck. In vitro endopeptidase activity analysis showed that mutating SENP1 Y270 to either phenylalanine (F) to mimic the phosphorylation-defective state or to glutamate (E) to mimic the negative charge of tyrosine phosphorylation in the enzyme microenvironment did not change its endopeptidase activity towards pre-SUMO1. However, SENP1 Y270E but not Y270F mutation exhibited decreased endopeptidase activity towards pre-SUMO3. Through in vivo isopeptidase activity analysis by rescue expression of SENP1 and its Y270 mutants in a SENP1 CRISPR knockout T cell line, we found that SENP1 Y270F downregulated its isopeptidase activity towards both SUMO1 and SUMO2/3 conjugation by reducing SENP1 binding with sumoylated targets. While overexpression of SENP1 inhibited TCR-induced IL-2 production, overexpression of SENP1 Y270F enhanced it instead. In summary, TCR-induced Y270 phosphorylation of SENP1 may promote its isopeptidase activity and specifically decrease its endopeptidase activity against pre-SUMO3, which finely tunes activation of T cells.

Leukocyte-Mediated Combined Targeted Chemo and Gene Therapy for Esophageal Cancer.

Poor prognosis of esophageal cancer is associated with limited clinical treatment efficacy and lack of targeted therapies. With advances in nanomedicine, nanoparticle drug delivery systems play increasingly important roles in tumor treatment by enabling the simultaneous delivery of multiple therapeutic agents. We here propose a novel nanovector for targeted combination gene therapy and chemotherapy in esophageal cancer. A novel lipid nanovector (EYLN) was designed to carry the chemotherapy drug doxorubicin (Dox) and small interfering RNA against the lipid anabolic metabolism gene LPCAT1, which we previously showed to be significantly overexpressed in esophageal cancer tissues, and its interference inhibited the proliferation, invasion, and metastasis of esophageal cancer cells. This vector, EYLN-Dox/siLPCAT1, was further coated with leukocyte membranes to obtain mEYLNs-Dox/siLPCAT1. The particle size of the coated nanovector was approximately 136 nm, and the surface zeta potential was -21.18 mV. Compared with EYLNs-Dox/siLPCAT1, mEYLNs-Dox/siLPCAT1 were more easily internalized by esophageal cancer cells due to the LFA-1 highly expressed leukocyte membrane coating and showed significant inhibition of the proliferation, migration, and metastasis of esophageal cancer cells, along with their LPCAT1 expression, through more effective delivery of the drugs. Moreover, the nanovectors showed improved blood circulation time, tissue distribution, tumor targeting, and tumor suppression in a mouse model. Thus, combining chemo and gene therapy with this new nanodelivery system achieved greater therapeutic efficacy, providing a new strategy for the treatment of esophageal cancer.

The p38-interacting protein p38IP suppresses TCR and LPS signaling by targeting TAK1.

Negative regulation of immunoreceptor signaling is required for preventing hyperimmune activation and maintaining immune homeostasis. The roles of p38IP in immunoreceptor signaling remain unclear. Here, we show that p38IP suppresses T-cell receptor (TCR)/LPS-activated NF-κB and p38 by targeting TAK1 kinase and that p38IP protein levels are downregulated in human PBMCs from rheumatoid arthritis (RA) patients, inversely correlating with the enhanced activity of NF-κB and p38. Mechanistically, p38IP interacts with TAK1 to disassemble the TAK1-TAB (TAK1-binding protein) complex. p38IP overexpression decreases TCR-induced binding of K63-linked polyubiquitin (polyUb) chains to TAK1 but increases that to TAB2, and p38IP knockdown shows the opposite effects, indicating unanchored K63-linked polyUb chain transfer from TAB2 to TAK1. p38IP dynamically interacts with TAK1 upon stimulation, because of the polyUb chain transfer and the higher binding affinity of TAK1 and p38IP for polyUb-bound TAB2 and TAK1, respectively. Moreover, p38IP scaffolds the deubiquitinase USP4 to deubiquitinate TAK1 once TAK1 is activated. These findings reveal a novel role and the mechanisms of p38IP in controlling TCR/LPS signaling and suggest that p38IP might participate in RA pathogenesis.

EP4 activation ameliorates liver ischemia/reperfusion injury via ERK1/2­GSK3ß­dependent MPTP inhibition.

Prostaglandin E receptor subtype 4 (EP4) is widely distributed in the heart, but its role in hepatic ischemia/reperfusion (I/R), particularly in mitochondrial permeability transition pore (MPTP) modulation, is yet to be elucidated. In the present study, an EP4 agonist (CAY10598) was used in a rat model to evaluate the effects of EP4 activation on liver I/R and the mechanisms underlying this. I/R insult upregulated hepatic EP4 expression during early reperfusion. In addition, subcutaneous CAY10598 injection prior to the onset of reperfusion significantly increased hepatocyte cAMP concentrations and decreased serum ALT and AST levels and necrotic and apoptotic cell percentages, after 6 h of reperfusion. Moreover, CAY10598 protected mitochondrial morphology, markedly inhibited mitochondrial permeability transition pore (MPTP) opening and decreased liver reactive oxygen species levels. This occurred via activation of the ERK1/2­GSK3ß pathway rather than the janus kinase (JAK)2­signal transducers and activators of transcription (STAT)3 pathway, and resulted in prevention of mitochondria­associated cell injury. The MPTP opener carboxyatractyloside (CATR) and the ERK1/2 inhibitor PD98059 also partially reversed the protective effects of CAY10598 on the liver and mitochondria. The current findings indicate that EP4 activation induces ERK1/2­GSK3ß signaling and subsequent MPTP inhibition to provide hepatoprotection, and these observations are informative for developing new molecular targets and preventative therapies for I/R in a clinical setting.

Nanovector Assembled from Natural Egg Yolk Lipids for Tumor-Targeted Delivery of Therapeutics.

Nanomedicine uses nanotechnology-based strategies for precision tumor therapy, including passive and ligand-mediated active tumor targeting by nanocarriers. However, the possible biotoxicity of chemosynthetic nanovectors limits their clinical applications. A novel natural egg yolk lipid nanovector (EYLN) was developed for effective loading and delivery of therapeutic agents. Lipids were extracted from egg yolks and reassembled into nanosized particles. EYLNs' stability, cellular uptake, toxicity, and delivery capacity for therapeutic agents were evaluated in vitro. The systemic toxicity and biodistribution of EYLNs were analyzed in normal mice, and the therapeutic effects of doxorubicin (Dox)-loaded EYLNs were evaluated in mouse breast cancer and hepatoma models. EYLNs had a particle size of ∼40 nm and a surface ζ-potential of -45 mV and were effectively internalized by tumor cells, without showing toxicity and side effects in vitro and in vivo. Importantly, their excellent permeability and retention effect significantly enhanced the distribution of EYLNs at tumor sites, and EYLN-Dox effectively inhibited the tumor growth in both mouse models. Targeted modification with folic acid further promoted vector-mediated drug distribution in tumors. This study demonstrates that lipids with specific proportions in the egg yolk can be used to construct natural drug vectors, providing a new strategy for nano-oncology research.

Aptamer-conjugated and doxorubicin-loaded grapefruit-derived nanovectors for targeted therapy against HER2+ breast cancer.

Increased human epidermal growth factor receptor 2 (HER2) expression is a hallmark of HER2+ breast cancer. HER2 promotes the growth of cancer cells and makes them particularly aggressive. Currently, trastuzumab is the only HER2-targeted therapeutic agent approved by the FDA for HER2-overexpressing breast cancer treatment. However, clinical efficacy of trastuzumab is limited greatly by the occurrence of drug resistance. In this study, an aptamer (HA1) specific for HER2-overexpressing breast cancer cells was selected using Cell-SELEX. This allowed the development of grapefruit-derived nanovectors (GNVs) conjugated with HA1 that targeted specifically HER2+ breast cancer cells. In vitro experiments demonstrated that HA1 effectively promoted the internalisation of GNVs into cancer cells and tumour spheroids. In vivo data showed that drug delivery to tumour tissues and antitumor activities were dramatically enhanced by conjugating HA1 with drug-loaded GNVs. This study indicates that aptamers mediating targeted drug delivery by GNVs represent a promising strategy for HER2+ breast cancer therapy.

Rate and Risk Factors of Superior Facet Joint Violation during Cortical Bone Trajectory Screw Placement: A Comparison of Robot-Assisted Approach with a Conventional Technique.

OBJECTIVE: To compare the incidence and risk factors of superior facet joint violation (FJV) during cortical bone trajectory screw placement in robot-assisted approach versus conventional technique. METHODS: A retrospective study, including 69 patients having cortical bone trajectory (CBT) screw instrumentation for symptomatic degenerated diseases or trauma, was conducted between June 2015 to January 2019. All patients underwent CBT surgery performed by the same team of experienced surgeons. Patients were randomly divided into two groups: a conventional group (CG, 46 cases) and a robot group (RG, 23 cases). The surgical robotic system was used for screw instrumentation in the robot group and the traditional screw instrumentation with fluoroscopic guidance was used in the conventional group. Cortical screws followed a medio-to-lateral path in the transverse plane and a caudal-to-cephalad path in the sagittal plane. Preoperative and postoperative computed tomography (CT) scans were obtained to determine the degree and incidence of FJV. The violation status of facet joint was evaluated according to the modified classification: grade 0, no violation; grade 1, screw shaft, screw head or rod within 1 mm of or abutting the facet joint, but did not enter the articular facet joint; grade 2, screw shaft, screw head or rod clearly in the facet joint. The following factors that may contribute to the occurrence of FJV were analyzed: age, sex, body mass index (BMI), proximal fusion level, fusion length, the side of screw, preoperative vertebral slip, superior facet angle, and degenerative scoliosis. The chi-squared test and Student's t-test were used for analysis of the variables for significance (P < 0.05). RESULTS: FJV occurred in 41.3% of patients in CG and 17.3% of patients in RG. A chi-squared analysis revealed a significantly lower rate of FJV for RG compared with CG (P = 0.04). In the CG, 17 of the 109 cephalad screws were grade 1 (15.6%), and five were grade 2 (4.6%). In the RG, three of the 46 cephalad screws were grade 1 (6.5%), and three were grade 2 (6.5%). There was a statistically significant difference in the incidence of FJV between the left and right screw with fluoroscopy-assisted CBT screw instrumentation (P < 0.05). A significant correlation between scoliosis with the FJV was found in CG (P < 0.05) and in RG (P < 0.05). With regard to superior facet angle, a measurement ≥45° was a significant risk factor of FJV in CG (P < 0.05) and in RG (P < 0.05). CONCLUSIONS: A robot-assisted approach could reduce the incidence of FJV compared with the conventional approach in CBT technique.

FKBP10 functioned as a cancer-promoting factor mediates cell proliferation, invasion, and migration via regulating PI3K signaling pathway in stomach adenocarcinoma.

As documented, the expression, biological roles, and prognostic significance of FKBP10 in stomach adenocarcinoma (STAD) have not been investigated till now. This drives us to detect the biological roles and clinical significance of FKBP10 in STAD. The expression level of FKBP10 was measured based on the data obtained from the TCGA, ONCOMINE, and GEPIA databases, and STAD cell lines. Through in vitro experiments, cell behaviors were investigated to evaluate the effects of FKBP10 on STAD. Moreover, the PI3K-AKT signaling pathway was measured. Relying on the data of TCGA, ONCOMINE, and GEPIA databases, and cancer cell lines, FKBP10 was up-regulated in STAD when compared with normals. The patients with low expression of FKBP10 had higher survival rate than those with high FKBP10 expression. After knockdown of FKBP10 in AGS cells, cell vitality, colony formation ability, and the migratory and invasive potential were inhibited. Western blotting analysis exhibited that knockdown of FKBP10 significantly reduced the expression level of p-AKT, and p-PI3K, but it did not influence the total expression level of AKT, and PI3K. FKBP10 might serve as a crucial player in gastric cancer, and targeting FKBP10 might provide clinical utility in gastric cancer in future.