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PURPOSE Diagnosis of AIDS lymphoma in low-resource settings, like South Africa, is often delayed, leaving patients with limited treatment options. In tuberculosis (TB) endemic regions, overlapping signs and symptoms often lead to diagnostic delays. Assessment of plasma cell-free DNA (cfDNA) by next-generation sequencing (NGS) may expedite the diagnosis of lymphoma but requires high-quality cfDNA. METHODS People living with HIV with newly diagnosed aggressive B-cell lymphoma and those with newly diagnosed TB seeking care at Chris Hani Baragwanath Academic Hospital and its surrounding clinics, in Soweto, South Africa, were enrolled in this study. Each participant provided a whole blood specimen collected in cell-stabilizing tubes. Quantity and quality of plasma cfDNA were assessed. NGS of the immunoglobulin heavy chain was performed. RESULTS Nine HIV+ patients with untreated lymphoma and eight HIV+ patients with TB, but without lymphoma, were enrolled. All cfDNA quantity and quality metrics were similar between the two groups, except that cfDNA accounted for a larger fraction of recovered plasma DNA in patients with lymphoma. The concentration of cfDNA in plasma also trended higher in patients with lymphoma. NGS of immunoglobulin heavy chain showed robust amplification of DNA, with large amplicons (> 250 bp) being more readily detected in patients with lymphoma. Clonal sequences were detected in five of nine patients with lymphoma, and none of the patients with TB. CONCLUSION This proof-of-principle study demonstrates that whole blood collected for cfDNA in a low-resource setting is suitable for sophisticated sequencing analyses, including clonal immunoglobulin NGS. The detection of clonal sequences in more than half of patients with lymphoma shows promise as a diagnostic marker that may be explored in future studies.

BACKGROUND Uretero-arterial fistula (UAF) is a disease that usually involves the aorta, common iliac artery, external iliac artery, hypogastric artery, and lumbar artery. Among them, uretero-lumbar artery fistula (ULAF) is the most unusual type. So, both in China and around the world, the diagnosis and treatment of ULAF is a big challenge. CASE SUMMARY A 55-year-old female patient with a history of pelvic radiotherapy developed unexplained massive hemorrhage during replacement of the right Resonance metallic ureteral double-J tubes due to a long-standing indwelling ureteral stent for ureteral stricture. Later, we found contrast extravasation from the patient's right L4 artery into the ureter under digital subtraction angiography (DSA) and administered polyvinyl alcohol particle embolic agent and coil embolization; hematuria was controlled. Follow-up investigations at 18 mo showed no sign of recurrence. CONCLUSION DSA is very important in the diagnosis and treatment of UAF, and DSA should be preferred when UAF is suspected. In addition, the use of softer ureteral stents in patients with primary disease and risk factors for UAF should be considered to avoid increasing the risk of the development of the disease; endovascular treatment should be preferred in patients who have developed UAF.

Recent neuroimaging studies have identified alterations in activity and connectivity among many brain regions as potential biomarkers for panic disorder. However, the functional connectome of panic disorder is not well understood. Therefore, a graph-theoretical approach was applied in this study to construct functional networks of patients and healthy controls in order to discover topological changes in panic disorder. 31 patients and 33 age and sex matched healthy controls underwent resting-state functional magnetic resonance imaging. Brain networks for each participant were structured using nodes from the Anatomical Automatic Labeling template and edges from connectivity matrices. Then, topological organizations of networks were calculated. Network-based statistical analysis was conducted, and global and nodal properties were compared between patients and controls. Unlike controls, patients with panic disorder displayed a small-world network. Patients also revealed decreased nodal efficiency in right superior frontal gyrus (SFG), middle frontal gyrus (MFG), right superior temporal gyrus (STG), and left middle temporal gyrus (MTG). Decreased functional connectivity was found in panic disorder between right MTG and extensive temporal regions. Among these disrupted regions, the decreased nodal efficiency of SFG showed a positive correlation with clinical symptoms while nodal betweenness centrality in angular gyrus showed a negative correlation. Our results indicated decreased function of global and regional information transmission in panic disorder and emphasized the role of temporal regions in its pathology.

Objectives To demonstrate clinicopathologic features and evaluate the clonality of double PIK3CA alterations in colorectal cancers (CRCs). Methods Clonality was examined in 13 CRCs with double PIK3CA alterations (1.7% of CRCs or 9.6% of PIK3CA-mutated CRCs). Multiregional analyses were performed to confirm subclonal PIK3CA alterations. Results PIK3CA alterations were detected within exon 9 (51%), exon 20 (23%), exon 1 (15%), and exon 7 (6.0%). CRCs with exon 7 alterations showed a significantly higher incidence of double PIK3CA alterations. Most double PIK3CA alterations consisted of a hotpsot alteration and an uncommon alteration; they were often clonal and present within a single tumor population. Multiregional analyses of CRCs with predicted subclonal double-alterations revealed multiclonal CRCs with divergent PIK3CA variant status originating from a common APC- and KRAS-mutated founder lineage of adenoma. Conclusions The findings supported multiclonal CRCs resulting from parallel evolution during the progression from adenoma to adenocarcinoma within the mitogen-activated protein kinase pathway, as previously demonstrated, or the mammalian target of rapamycin pathway. Further studies are warranted to elucidate clinical significance and potential targeted therapy for CRC patients with double PIK3CA alterations and impacts on clinical decision-making in patients with multiclonal CRCs harboring divergent PIK3CA mutational status.

The effects of transmembrane protein 119 (TMEM119) on breast cancer progression have not been elucidated. This study aims to investigate the roles of TMEM119 in breast cancer progression. Clinical samples and online datasets were used to determine TMEM119 expression and its correlation between patients’ survival. Wound healing, transwell invasion, mammary spheroid formation, and ALDH activity were performed to detect the effects of TMEM119. RNA-sequencing, Luciferase report analysis, Co-IP, and ChIP analysis were constructed to reveal the underlying mechanisms. We found that TMEM119 was highly expressed in breast cancer tissues and cells compared to that in normal tissues and cells. Additionally, TMEM119 expression was negatively correlated with the survival of breast cancer patients. TMEM119 knockdown reduced the expression of stemness markers, mammary spheroid-formation ability and ALDH activity. RNA-sequencing analysis indicated that Wnt/β-catenin signaling was enriched in cells with TMEM119 overexpression. Further co-IP experiments indicated that TMEM119 interacted with β-catenin and maintained its protein stability. Conversely, β-catenin directly bound to TMEM119 gene promoter and thus increased TMEM119 transcriptional activity and its expression. Finally, we demonstrated that TMEM119-mediated effects depended on Wnt/β-catenin signaling. Thus, this work reveals a novel TMEM119-β-catenin positive feedback loop essential for breast cancer cell stemness.

Background Evidence of the efficacy of Shenfu injection (SFI) in the treatment of heart failure (HF) is inconsistent. This study aimed to strictly evaluate the methodological quality, reporting quality, and evidence quality of systematic reviews (SRs) and meta-analyses (MAs) on the efficacy of SFI. Methods From inception to December 2020, using standardized search strategies, we searched for relevant SRs and MAs in the following seven databases: Cochrane library, Embase, PubMed, SinoMed, China National Knowledge Infrastructure (CNKI), Wanfang Database, and VIP Database. The Appraisal Tool for Systematic Reviews of Randomized and Observational Studies 2 (AMSTAR-2) and Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) tools were used to evaluate the methodological and reporting quality of SRs, respectively. The quality of results was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. If necessary, we conducted quantitative synthesis or descriptive analysis of the original data. Results There were 12 SRs/MAs involving 302 original randomized controlled trials (RCTs) and more than 22,445 participants (the total number was not mentioned in 1 study). The treatment group was classified as SFI combined with western medicine (WM), while the control group was WM alone. The methodological quality of all the literatures was very low, and the quality of reports was relatively good, with an average PRISMA score of 18.25 points. We evaluated 52 outcomes, of which 3 were moderate quality, 13 were low quality, and the rest were very low quality. Low quality evidences indicated that the clinical efficacy of SFI combined with WM for HF was better than that of WM, which can improve the quality of life and cardiac function of patients. Conclusions It appeared that SFI was effective in the treatment of HF. Due to the low quality of methodology and reports in the literature, we cannot be sure of the results. We strongly recommend that more high-level RCTs be carried out in the future. Besides, researchers should strictly comply with the AMSTAR-2, PRISMA, and GRADE guidelines for SRs.

t(6;9)(p22;q34.1)/DEK-NUP214 is a recurrent genetic abnormality that occurs in 1-2% of patients with acute myeloid leukemia (AML), and rarely in myelodysplastic syndrome (MDS). It has been suggested by others that all myeloid neoplasms with t(6;9)/DEK-NUP214 may be considered as AML, even when blast count is

Naturally-derived metallo-bacteriochlorophylls have attracted much attention since their clinical approval for cancer photodynamic therapy. Their therapeutic properties are rooted in the metal complexation of bacteriochlorophylls, which endows them with optical properties favourable for biophotonic and biomedical applications, including near-infrared light-activated reactive oxygen species generation at therapeutic levels. Despite these advantages, the utility of these chromophores has been limited by synthetic challenges associated with bacteriochlorophyll metallation; specifically, a slow reaction rate and necessity of complex purification procedures remain barriers towards metalated bacteriochlorophyll synthesis. Here, these limitations are overcome through the development of a new fast, facile, efficient, base-free microwave heating metallation method for the synthesis of a series of metallo (Pd, Cu, Zn, Cd, Sn, In, Mn, Co) bacteriopyropheophorbides. The preparation and structural and optical spectral characterization of these complexes are presented. This microwave-enabled synthetic method is then applied to generate the clinical photosensitizer agent Pd-bacteriopheophorbide (TOOKAD) effectively and efficiently, followed by validation of its metallation-enhanced ROS generation.

The presence of increased multinucleated megakaryocytes (aka osteoclast-like) is considered a dysplastic feature in myelodysplastic syndrome; however, its clinical significance in isolation is uncertain. Herein, we report the clinicopathologic and genetic features of 18 such cases of 40,539 bone marrow biopsies spanning 10 years. All 18 patients had ≥25% multinucleated megakaryocytes in otherwise normal bone marrow biopsies, which were evaluated for plasma cell neoplasms (n=9), lymphoma (n=4), or anemia/neutropenia (n=5). None of the 17 patients tested showed acquired cytogenetic abnormalities. Sixteen patients underwent targeted gene panel next-generation sequencing: 9 patients had no pathogenic mutations; 3 harbored a single pathogenic mutation with variant allele frequencies of 7.5%, 7.6%, and 10.7%, likely representing clonal hematopoiesis of indeterminate potential; 1 had 2 pathogenic mutations, 1 of which had a variant allele frequency >20%. Fourteen of 18 patients had a follow-up period >6 months (median: 36.5 mo, range: 7 to 110 mo) and no patients developed a new-onset cytopenia, a progressive cytopenia, or a myeloid neoplasm. The patient with 2 mutations had persistent anemia, worrisome for an emerging MDS. However, given the absence of thrombocytopenia, increased multinucleated megakaryocytes in this patient could be an unrelated incidental finding. Our study indicates that increased multinucleated megakaryocytes as an isolated finding is a rare phenomenon, and this sole morphologic finding is not diagnostic of myelodysplastic syndrome. Diagnostic approaches in the presence of increased multinucleated megakaryocytes are proposed based on different clinical and pathologic scenarios.

Penile dorsal nerve somatosensory evoked potential (DNSEP) is a scientific and objective technique that provides effective and objective data to establish the diagnosis of premature ejaculation (PE).To explore differences in DNSEP between patients with primary premature ejaculation (PPE) and those with secondary premature ejaculation (SPE), in order to investigate the clinical value of DNSEP in the diagnosis of PE.The participants were divided into a PPE group (34 cases), an SPE group (25 cases) and a healthy control group (18 cases). All participants underwent DNSEP testing, and the latencies and amplitudes of DNSEP were recorded.Differences in the latencies and amplitudes of DNSEP were compared among the PPE, SPE, and healthy control groups.The latencies of DNSEP in the PPE and SPE groups were shorter than those in the healthy control group, and these differences were statistically significant (P0.01). However, there was no statistically significant difference between the PPE and SPE groups (P0.05). The amplitudes of DNSEP in the PPE group were significantly higher than those in the healthy control group (P0.01). However, the amplitudes of DNSEP in the SPE group were significantly lower than those in the healthy control group (P0.05).PPE and SPE can be differentiated based on differences in the amplitudes of DNSEP, providing an objective basis for treatments and follow-up examinations.We evaluated differences in the amplitudes of DNSEP between PPE and SPE patients, which were rare in the published literature. However, specific causes of these differences are still unclear. SEP only reflects afferent pathways in the ejaculatory reflex arc, and role of the brain as a higher center should not be ignored.Both PPE and SPE patients are characterized by an increased excitability of the penile sensory nerves. Sun Z, Liao Z, Zheng Q, et al. A Study of Differences in Penile Dorsal Nerve Somatosensory Evoked Potential Testing Among Healthy Controls and Patients With Primary and Secondary Premature Ejaculation. J Sex Med Rev 2021;18:732-736.

Prior investigations have revealed that the stress characteristics of columns at different locations beneath an embankment vary. A failed column releases stress and causes significant increases in the stresses within neighbouring columns, possibly leading to progressive failure of adjacent columns and global failure of the embankment. Prior studies have presented insights into the progressive failure of column-supported embankments. However, limited insight has been provided into the progressive failure mechanism of geosynthetic-reinforced and rigid column-supported embankments. In this technical note, the effects of geosynthetic reinforcement on progressive failure are numerically analysed. A comparison of the progressive failure of rigid columns with and without geosynthetic reinforcement is first conducted. The restraining effects of geosynthetics on progressive failure of the columns and the influence of geosynthetic tensile stiffness on embankment stability are analysed. The results reveal that progressive failure is primarily governed by the distribution of the bending moment and the axial force within the columns. To further investigate the contribution of geosynthetics to resisting progressive failure of rigid columns, the internal forces in the columns and tensile strains in the geosynthetics are discussed.

Incompressible dipping substrata are commonly encountered in engineering practice. Compared to horizontal underlying strata, the inclined underlying stratum increase the risk of collapse of embankments reinforced with columns because it weakens the restraint of the column base. The objective of this study is to investigate the effectiveness of geosynthetics on improving the embankment stability when the underlying stratum is inclined. The influence of geosynthetic tensile stiffness on the ultimate surcharge and failure mechanism is studied. A deep-seated failure with column tilting occurs when the geosynthetic tensile stiffness is low, whereas a lateral sliding occurs when the geosynthetic tensile stiffness is high. To illustrate the contribution of geosynthetics, the distribution of the lateral pressures acting on the columns is analyzed.

The 0.2% strain offset approach is mostly used to calculate the yield stress and serves as an efficient method for cross-lab comparisons of measured material properties. However, it is difficult to accurately determine the yield of the bone. Especially when computational models require accurate material parameters, clarification of the yield point is needed. We tested 24 cortical specimens harvested from six bovine femora in three-point bending mode, and 11 bovine femoral cortical specimens in the tensile mode. The Young's modulus and yield stress for each specimen derived from the specimen-specific finite element (FE) optimization method was regarded as the most ideal constitutive parameter. Then, the strain offset optimization method was used to find the strain offset closest to the ideal yield stress for the 24 specimens. The results showed that the 0 strain offsets underestimated (- 25%) the yield stress in bending and tensile tests, while the 0.2% strain offsets overestimated the yield stress (+ 65%) in three-point bending tests. Instead, the yield stress determined by 0.007 and 0.05% strain offset for bending and tensile loading respectively, can effectively characterize the biomechanical responses of the bone, thereby helping to build an accurate FE model.

The imbalance between the anabolism and catabolism of the extracellular matrix (ECM) is of great importance to osteoarthritis (OA) development. Aberrant inflammatory responses and hypertrophic changes of chondrocytes are the main contributors to these metabolic disorders. In the present study, we found that Oroxylin A (ORA), a flavonoid compound derived from Oroxylum indicum, maintained ECM hemostasis of chondrocytes by Interleukin-1β (IL-1β) stimulation. Besides, it was demonstrated that IL-1β induced over-production of inflammatory mediators was attenuated by ORA treatment. Moreover, ORA could rescue IL-1β mediated hypertrophic alterations of chondrocytes. Mechanistically, ORA's protective effects were found to be associated with both NF-κB and Wnt/β-catenin signaling inhibition. Meanwhile, molecular docking analysis revealed that ORA could strongly bind to the inhibitor kappa B kinaseβ (IKKβ) and dishevelled, Dsh Homolog 2 (Dvl2), the upstream molecules of the NF-κB axis and β-catenin axis, respectively. In addition, ORA driven chondroprotective effects were also affirmed in a surgically induced OA mouse model. Taken together, the current study suggested that ORA might be a promising therapeutic option for the treatment of OA.

Background Paratesticular liposarcoma accounts for approximately 7% of scrotal tumors. They are rare lesions of the reproductive system with approximately 90% of the lesions originating from the spermatic cord. Surgery, with the goal of complete resection, is the mainstay for treatment of this disease. However, treatment consisting of extended resection to decrease local recurrence remains controversial. Case summary We report the cases of two patients with paratesticular liposarcomas who were treated with radical testicular tumor resection without adjuvant therapy. Follow-up investigations at 9 mo showed no sign of recurrence. Conclusion Surgery is the first-line treatment, regardless of whether it is a recurrent or primary tumor. Extended resection carries a higher risk of complications and should not be performed routinely. Preoperative radiotherapy can reduce the local recurrence rate without affecting the overall survival.

Oxidative stress-mediated excessive apoptosis and senescence of chondrocytes are the main pathological alterations in the osteoarthritis (OA) development. The protective effects of theaflavin (TF), a common group of polyphenols in black tea, against many degenerative diseases by attenuating oxidative stress are well reported. Nevertheless, its role in the OA treatment is still scantily understood. In the current research, by applying enzyme-linked immunosorbent assay (ELISA) kits and immunofluorescent staining, TF treatment was found to inhibit tert-Butyl hydroperoxide (TBHP)-induced imbalance of anabolism and catabolism in primary mouse chondrocytes. Then, according to western blot, live-dead staining, and SA-β-gal staining, the dramatically increased level of apoptosis and senescence of chondrocytes in response to TBHP was also found to be reduced by TF administration. With regard to upstream signaling investigation, the in vitro molecular binding analysis indicated that the beneficial effects of TF might be related to the regulation of the Keap1/Nrf2/HO-1 axis. Furthermore, the Silencing of Nrf2 resulted in the abolishment of the anti-apoptosis and anti-senescence effects of TF. In addition, the oral administration of TF was demonstrated to ameliorate osteoarthritis development in a surgically induced mouse OA model. Taken together, these results suggest that TF might be a promising therapeutic option for the treatment of OA.

Background Establishing the efficacy of novel photosensitizers (PSs) for phototherapy of lung cancer requires in vivo study prior to clinical evaluation. However, previously described animal models are not ideal for assessing transbronchial approaches with such PSs. Methods An ultra-small parallel-type composite optical fiberscope (COF) with a 0.97 mm outer diameter tip. The integration of illumination and laser irradiation fibers inside the COF allows simultaneous white-light and fluorescence imaging, as well as real-time monitoring of tip position during laser phototherapy. An orthotopic lung cancer mouse model was created with three human lung cancer cell lines transbronchially inoculated into athymic nude mice. The COF was inserted transbronchially into a total of 15 mice for tumor observation. For in vivo fluorescence imaging, an organic nanoparticle, porphysome, was used as a PS. Laser excitation through the COF was performed at 50 mW using a 671 nm source. Results The overall success rate for creating orthotopic lung tumors was 71%. Transbronchial white light images were successfully captured by COF. Access to the left main bronchus was successful in 87% of mice (13/15), the right main bronchus to the cranial lobe bronchus level in 100% (15/15), and to the right basal trifurcation of the middle lobe, caudal lobe and accessory lobe in 93% (14/15). For transbronchial tumor localization of orthotopic lung cancer tumors, PS-laden tumor with the strong signal was clearly contrasted from the normal bronchial wall. Conclusions The ultra-small COF enabled reliable transbronchial access to orthotopic human lung cancer xenografts in vivo. This method could serve as a versatile preclinical research platform for PS evaluation in lung cancer, enabling transbronchial approaches in in vivo survival models inoculated with human lung cancer cells.

Organ transplantation has been employed upon serious injuries, but a T-cell-mediated potent inflammatory immune response often leads to graft rejection. Immunosuppressive drugs such as rapamycin (RAPA) have to be taken after organ transplantation, but long-term use of these drugs causes severe adverse effects. Immune checkpoint pathways such as the programmed death-receptor 1/programmed death-ligand 1 (PD-1/PD-L1) provides an immunosuppressive environment, preventing excessive tissue destruction due to inflammatory immune responses. In this study, we bioengineered cell membrane-derived PD-L1 nanovesicles (PD-L1 NVs) to carry low doses of RAPA. These NVs inhibited T-cell activation and proliferation in vitro, by enhancing the PD-1/PD-L1 immune co-inhibitory signaling axis and inhibiting the mTOR pathway. Importantly, PD-L1 NVs encapsulated with rapamycin exerted stronger effects on inhibiting T-cell proliferation than PD-L1 NVs or rapamycin alone. This can be recapitulated in a mouse skin transplantation model, leading to the weakened alloimmune response and allograft tolerance. We also found that PD-L1/rapamycin vesicles have additional function to induce regulatory T cells in the recipient spleens. Our study highlighted the power of combining low-dose rapamycin and PD-L1 in the nanovesicles as immunosuppressants to promote allograft acceptance.

Pericarditis is a common clinical pericardial disease with complex etiology, pathogenesis, and high recurrence rate. Interleukin-1 is an important inflammatory cytokine, which regulates the occurrence and development of inflammation by regulating IL-1?, IL-1?, and IL-1RA; it plays an important role in pericarditis. In traditional Chinese medicine, the modern understanding of its etiology and pathogenesis has been improved. In this review, the etiology and pathogenesis of pericarditis are discussed from the perspective of traditional Chinese and Western medicine.

Understanding the precise intracellular localization of lead (Pb) is a key in deciphering processes in Pb-induced toxicology. However, it is a great challenge to trace Pbin vitro, especially in cultured cells. We aimed to find an innovative and efficient approach to investigate distribution of Pb in cells and to validate it through determining the subcellular Pb content. We identified its ultra-structural distribution with autometallography under electron microscopy in a choroidal epithelial Z310 cell line. Electron microscopy in combination with energy-dispersive X-ray spectroscope (EDS) was employed to provide further evidence of Pb location. In addition, Pb content was determined in the cytosol, membrane/organelle, nucleus and cytoskeleton fractions with atomic absorption spectroscopy. Pb was found predominantly inside the nuclear membranes and some was distributed in the cytoplasm under low-concentration exposure. Nuclear existence of Pb was verified by EDS under electron microscopy. Once standardized for protein content, Pb percentage in the nucleus fraction reached the highest level (76%). Our results indicate that Pb is accumulated mainly in the nucleus of choroid plexus. This method is sensitive and precise in providing optimal means to study the ultra-structural localization of Pb forin vitromodels. In addition, it offers the possibility of localization of other metals in cultured cells. Some procedures may also be adopted to detect target proteins via immunoreactions.

This study was evaluating how three desensitizing toothpastes used at home influence the effect associated with desensitizing agents after application in the clinic. Fifty dentine disks measure it permeability and 32 dentine disks with similar permeability levels were selected. Following Dental desensitizer treatment, dentine disks were randomly divided into three subgroups (n=10) that received applications of three toothpastes, respectively. The permeability (Lp) of each specimen was measured after each treatment. One specimen was selected from each group for scanning electron microscopy (SEM) observation. After each treatment, the Lp values decreased significantly for each group (p 0.05). After using the Dental desensitizer, Sensodyne, Crest and Colgate desensitizing toothpastes both can continued to reduce the permeability of the dentine disk, and no significant differences were found amongst them.

Enhanced recovery after surgery (ERAS) pathways are well established in certain surgical specialties because findings have shown significant improvements in outcomes. Convincing literature in head and neck cancer (HNC) surgery is lacking. This study aimed to assess the effect of an ERAS pathway on National Surgical Quality Improvement Program (NSQIP)-based occurrences and pain-related outcomes in HNC surgery. The study matched 200 patients undergoing head and neck oncologic surgery on an ERAS pathway between 1 March 2016 and 31 March 2019 with control subjects (1:1 ratio) during the same period. Demographic and perioperative data collected from the NSQIP database were extracted. Pain scores and medication usage were electronically extracted from our electronic medical record system and compared. Risk factors for high opioid usage also were assessed. Both groups were statistically similar in baseline characteristics. The ERAS group had fewer planned intensive care unit (ICU) admissions (4% vs. 14%; p

Objective: It has been demonstrated that performing percutaneous coronary intervention (PCI) in the absence of mechanical circulation support (MCS) for patients with complex high-risk coronary artery disease bears a high risk. Alternatively, to figure out the procedure effectiveness and the mid-term prognosis of PCI for complex high-risk coronary artery disease, we accomplished the whole process by the assistance of extracorporeal membrane oxygenation (ECMO). Methods: Between July 2016 and October 2017, 6 consecutive complex and high-risk coronary disease patients underwent routine ECMO-supported PCI. Results: The average age of the patients was 70.5±11.98, and half of them (50%) were male. The mean creatinine (Cr) was 188.67±151.68 µmol/L. The average scores for SYNTAX, SYNTAX II, and LVEF pre the procedure was 41.33±12.14, 47.87±9.45 / 31.55±8.82, and 44.40±12.58%, respectively. The mean supporting duration of ECMO was 10.50±7.79 h. Regarding the postoperative complication, one case observed lower limp venous thrombosis and another reported infection at the access site. Two patients (33.3%) died for refractory heart failure during the follow-up course of 17.00±9.51 months, and the average net improvement index (NII) was 28.30±25.11% for this period. Conclusion: With the support of ECMO, the prognosis of complex high-risk coronary disease has shown to be improved by intervention in our study.

Background. Period genes are important core clock genes, including PER1, PER2, and PER3. A number of studies have demonstrated that the abnormal expression of the PER gene family of clock genes is associated with the survival and prognosis of patients with cancer; however, the sample sizes included in the majority of these studies were small, and the reported results were inconsistent. This study was the first to collect the relevant publications to systematically evaluate the value of the expression of the PER gene family in the prediction of survival and prognosis of human tumors. Methods. The PubMed, Cochrane Library, Embase, and Web of Science databases were searched systematically, and a meta-analysis was performed. Results. A total of 12 eligible publications met the inclusion criteria for the meta-analysis, including 1,369 patients and 9 different types of cancer. The pooled hazard ratio for overall survival indicated that the overall survival of patients in the high PER1, PER2, and PER3 protein expression group was significantly higher than that in the low-expression group, respectively. The sensitivity analysis revealed that the result was stable and reliable. The association between PER1 and PER3 mRNA expression levels and cancer prognosis was not meta-analyzed as the number of experimental studies was PER2 mRNA and the overall survival of patients with cancer. Conclusion. PER1, PER2, and PER3 protein expression levels can be used as novel potential biomarkers for predicting cancer prognosis.

Nanoparticle delivery to solid tumours over the past ten years has stagnated at a median of 0.7% of the injected dose. Varying nanoparticle designs and strategies have yielded only minor improvements. Here we discovered a dose threshold for improving nanoparticle tumour delivery: 1 trillion nanoparticles in mice. Doses above this threshold overwhelmed Kupffer cell uptake rates, nonlinearly decreased liver clearance, prolonged circulation and increased nanoparticle tumour delivery. This enabled up to 12% tumour delivery efficiency and delivery to 93% of cells in tumours, and also improved the therapeutic efficacy of Caelyx/Doxil. This threshold was robust across different nanoparticle types, tumour models and studies across ten years of the literature. Our results have implications for human translation and highlight a simple, but powerful, principle for designing nanoparticle cancer treatments. Efficient nanoparticle delivery into tumours has been a challenge in the field. It is now shown that the efficiency can be improved substantially when the dose breaches a specific threshold.

Dehydrocorydaline (DHC) is an alkaloid isolated from Corydali syanhusuo that exhibits antitumor properties. It has been reported that DHC can inhibit the proliferation of breast cancer cells, however the underlying molecular mechanism remains elusive. Therefore, the main objective of this study was to evaluate the antitumor activity of DHC, and gain further insights into its mechanism of action. The viability of MDA-MB-231 cells was determined through a Cell Counting Kit-8 assay. The effect of DHC on the proliferation of MDA-MB-231 cells was detected by flow cytometry and 5-ethynyl-2′-deoxyuridine staining. Apoptosis was evaluated by Annexin V-FITC and PI staining through flow cytometry. The impact of DHC treatment on the colony-forming ability of breast cancer cells was assessed. The expression levels of proliferation-associated genes cyclin-dependent kinases 1 (CDK1) and cyclin D1 (CCND1) and apoptosis-related genes BCL2 and caspases 3/8/9 were quantified by real-time PCR. Western blot analysis was performed to evaluate the production of cleaved caspase 3/9 and matrix metalloproteinase (MMP)2/9. DHC-treated MDA-MB-231 cells were subcutaneously injected into mice. Subsequent immunohistochemical analyses were performed. DHC inhibited the viability, proliferation, colony-forming ability and migration of MDA-MB-231 cells; in addition, DHC treatment promoted their apoptosis. DHC inhibited the production of proliferation- and anti-apoptosis-associated proteins CDK1, CCND1, BCL2 as well as that of the metastasis-associated proteins MMP2 and MMP9. However, it promoted the expression of the pro-apoptotic caspases 3/8/9. Moreover, DHC inhibited the growth of MDA-MB-231 tumor xenografts in SCID mice, and decreased cell proliferation in newly formed tumors in vivo. DHC exerted anticancer effects by downregulating cell proliferation, antiapoptosis, metastasis-associated proteins CDK1, CCND1, BCL2 and metastasis-associated proteins MMP2 and MMP9, and by upregulating the expression of proapoptotic proteins caspase 3/8/9.

Background Primary colorectal cancer (PCRC) is one of the most common malignant tumors in clinic, and is characterized by high heterogeneity occurring between tumors and intracellularly. Therefore, this study aimed to explore potential gene targets for the diagnosis and treatment of PCRC via bioinformatic technology. Methods Gene Expression Omnibus (GEO) was used to download the data used in this study. Differently expressed genes (DEGs) were identified with GEO2R, and the gene set enrichment analysis (GSEA) was implemented for enrichment analysis. Then, the researchers constructed a protein-protein interaction (PPI) network, a significant module, and a hub genes network. Results The GSE81558 dataset was downloaded, and a total of 97 DEGs were found. There were 23 up-regulated DEGs and 74 down-regulated DEGs in the PCRC samples, compared with the control group. The PPI network included a total of 42 nodes and 63 edges. One module network consisted of 11 nodes and 25 edges. Another module network consisted of 4 nodes and 6 edges. The hub genes network was created by cytoHubba using GCG, GUCA2B, CLCA4, ZG16, TMIGD1, GUCA2A, CHGA, PYY, SST, and MS4A12. Conclusions Ten hub genes were found from the genomic samples of patients with PCRC and normal controls by bioinformatics analysis. The hub genes might provide novel ideas and evidence for the diagnosis and targeted therapy of PCRC.

Detection of coexisting mutations within the same signal transduction pathway, which are expected to be mutually exclusive, raises a concern of laboratory errors. We have previously confirmed the presence of different RAS (KRAS and NRAS) mutations in the adenoma and/or adenocarcinoma subpopulations of colorectal cancers (CRCs). In this study, multiregional analyses by next-generation sequencing were conducted to elucidate the mechanisms underlying multiple RAS mutations seen in 5 CRC specimens. Multiregional analyses were initially conducted in a single tissue block originally submitted for mutational profiling. In 2 specimens, mutational status of the APC gene was not identical, indicating collisional adenoma and adenocarcinoma. In 3 specimens, the same APC mutation was present in different subpopulations with divergent RAS mutations, indicating a common clonal origin. Subsequent comprehensive multiregional analyses of additional adenoma and adenocarcinoma components revealed multiclonal CRCs with divergent histomorphological features and RAS mutations originating from a common APC-mutated founder lineage of adenoma, but from different RAS-mutated founder lineages of adenocarcinoma. These findings are consistent with the stepwise model of colorectal tumorigenesis along with parallel evolution, which affects RAS genes within the mitogen-activated protein kinase pathway and occurs during the progression from adenomas to adenocarcinomas. Evaluation of tumor subpopulations with divergent histomorphological features by pathologists may help identify multiclonal CRCs. Further studies are warranted to evaluate the incidence of multiclonality in CRCs and its impact on clinical outcomes. Perhaps, multiclonal CRCs originating from the same APC-mutated founder lineage of adenoma but from different RAS-mutated founder lineages of adenocarcinomas should be defined and managed as separate CRCs.

Patients with advanced hepatocellular carcinoma (HCC) are often unable to tolerate chemotherapy due to liver dysfunction in the setting of cirrhosis. We investigate high‐density lipoprotein (HDL)‐mimicking peptide phospholipid scaffold (HPPS), which are nanoparticles that capitalize on normal lipoprotein metabolism and transport, as a solution for directed delivery of small interfering RNA (siRNA) cargo into HCC cells. Spalt‐like transcription factor 4 (SALL4), a fetal oncoprotein expressed in aggressive HCCs, is specifically targeted as a case study to evaluate the efficacy of HPPS carrying siRNA cargo. HPPS containing different formulations of siRNA therapy against SALL4 were generated specifically for HCC cells. These were investigated both in vitro and in vivo using fluorescence imaging. HPPS‐SALL4 effectively bound to scavenger receptor, class B type 1 (SR‐BI) and delivered the siRNA cargo into HCC cells, as seen in vitro. HPPS‐SALL4 effectively inhibited HCC tumor growth (P, Patients with advanced HCC are often unable to tolerate chemotherapy due to liver dysfunction in the setting of cirrhosis. We herein investigate High‐density Lipoprotein (HDL)‐mimicking Peptide Phospholipid Scaffold (HPPS), nanoparticles that capitalize on normal lipoprotein metabolism and transport, as a solution for directed delivery of RNA interference (siRNA) cargo into HCC cells. Our HDL‐like nanoparticles effectively inhibit HCC tumor growth without any systemic immunogenicity and avoid the need for hepatic metabolism in this cancer that develops in the setting of cirrhosis and liver dysfunction. Therefore, these natural lipoprotein‐like nanoparticles with RNA interference therapy are a promising therapeutic strategy for HCC.

In this study, we propose the use of surface-enhanced Raman spectroscopy (SERS) to determine spectral markers for recognition of heparin-induced thrombocytopenia (HIT), a difficult-to-diagnose immune-related complication that often leads to limb ischemia and thromboembolism. The ability to produce distinct molecular signatures without requiring addition of exogenous labels enables unbiased inquiry and makes SERS an attractive complementary diagnostic tool for various complex pathologies. Here, we report a new capillary tube-derived SERS platform that offers ultrasensitive, label-free measurement capability as well as efficient handling of blood serum samples. The developed platform shows excellent reproducibility and long-term stability and, crucially, provides an alternative diagnostic rubric for determination of HIT by leveraging machine-learning based classification of the spectroscopic data. We envision that a portable Raman instrument could be combined with the capillary tube-based SERS analytical tool for rapid determination of HIT in the clinical laboratory - without perturbing the existing diagnostic workflow.

The incidence of differentiated thyroid cancer has increased significantly during the last several decades. Surgical resection is the primary treatment for thyroid cancer and is highly effective, resulting in 5-year survival rates greater than 98%. However, surgical resection can result in short- and long-term treatment-related morbidities. Additionally, as this malignancy often affects women less than 40 years of age, there is interest in more conservative treatment approaches and, an unmet need for therapeutic options that minimize the risk of surgery-related morbidities while simultaneously providing an effective cancer treatment. Photodynamic therapy (PDT) has the potential to reduce treatment-related side effects by decreasing invasiveness and limiting toxicity. Owing to multiple advantageous properties of the porphyrin-HDL nanoparticle (PLP) as a PDT agent, including preferential accumulation in tumor, biodegradability and unprecedented photosensitizer packing, we evaluate PLP-mediated PDT as a minimally invasive, tumor-specific treatment for thyroid cancer. On both a biologically relevant human papillary thyroid cancer (K1) mouse model and an anatomically relevant rabbit squamous carcinoma (VX2)-implanted rabbit thyroid model, the intrinsic fluorescence of PLP enabled tracking of tumor preferential accumulation and guided PDT. This resulted in significant and specific apoptosis in tumor tissue, but not surrounding normal tissues including trachea and recurrent laryngeal nerve (RLN). A long-term survival study further demonstrated that PLP-PDT enabled complete ablation of tumor tissue while sparing both the normal thyroid tissue and RLN from damage, thus providing a safe, minimally invasive, and effective alternative to thyroidectomy for thyroid cancer therapies.