A Bibliometric Analysis of Exosomes Therapy in the Treatment of Osteoarthritis from 2012 to 2022.

Purpose: Osteoarthritis (OA) is a common clinical disease characterized by the destruction of articular cartilage, subchondral ossification, cystic degeneration and osteophyte formation. Recently, more and more scholars draw attention to exosomes in the field of OA, and exciting breakthroughs have been achieved in recent years. However, bibliometric analysis of the literature in this research field is lacking. Considering its potential in treatment of OA, this article aimed to analyze the research status and identify future hotspots of exosomes in osteoarthritis in recent 10 years by bibliometrics tools. Methods: Relevant publications in this field from 2012 to 2022 was retrieved from the Web of Science core collection database (WOSSCC). And we used Vosviewers, CiteSpace, an online analysis platform and the R package "Bibliometrix" for bibliometric analysis. Results: A total of 484 publications (including 319 articles and 165 reviews) from 51 countries, 720 institutions, were included in this study. IRCCS Ist Ortoped Galeazzi, Shanghai Jiao Tong University, and Sun Yat-sen University are the leading research institutions in this field. International Journal of Molecular Sciences contributed the largest number of articles, and Osteoarthritis and Cartilage is the most co-cited journal. Of the 2664 scholars who participated in the study, Ragni E, De Girolamo L, Orfei CP, and Colombini A had the largest number of articles. Zhang, SP is the most co-cited author. "Mesenchymal stem cell", "biomaterials", "Inflammation" and "regenerative medicine" are the keywords in the research. Conclusion: This is the first bibliometric analysis of exosomes in osteoarthritis. We explored current research status in recent years and identified frontiers and hot spots in this research field. We highlight the significant roles of mesenchymal stem cell-derived exosomes (MSC-Exos) in the treatment of osteoarthritis, and identified exosomal biomaterials as frontier in this research domain, which can provide reference for the researchers who focus on this research field.

The marriage of immunomodulatory, angiogenic, and osteogenic capabilities in a piezoelectric hydrogel tissue engineering scaffold for military medicine.

BACKGROUND: Most bone-related injuries to grassroots troops are caused by training or accidental injuries. To establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroots troops, it is imperative to develop new strategies and scaffolds to promote bone regeneration. METHODS: In this study, a porous piezoelectric hydrogel bone scaffold was fabricated by incorporating polydopamine (PDA)-modified ceramic hydroxyapatite (PDA-hydroxyapatite, PHA) and PDA-modified barium titanate (PDA-BaTiO3, PBT) nanoparticles into a chitosan/gelatin (Cs/Gel) matrix. The physical and chemical properties of the Cs/Gel/PHA scaffold with 0-10 wt% PBT were analyzed. Cell and animal experiments were performed to characterize the immunomodulatory, angiogenic, and osteogenic capabilities of the piezoelectric hydrogel scaffold in vitro and in vivo. RESULTS: The incorporation of BaTiO3 into the scaffold improved its mechanical properties and increased self-generated electricity. Due to their endogenous piezoelectric stimulation and bioactive constituents, the as-prepared Cs/Gel/PHA/PBT hydrogels exhibited cytocompatibility as well as immunomodulatory, angiogenic, and osteogenic capabilities; they not only effectively induced macrophage polarization to M2 phenotype but also promoted the migration, tube formation, and angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) and facilitated the migration, osteo-differentiation, and extracellular matrix (ECM) mineralization of MC3T3-E1 cells. The in vivo evaluations showed that these piezoelectric hydrogels with versatile capabilities significantly facilitated new bone formation in a rat large-sized cranial injury model. The underlying molecular mechanism can be partly attributed to the immunomodulation of the Cs/Gel/PHA/PBT hydrogels as shown via transcriptome sequencing analysis, and the PI3K/Akt signaling axis plays an important role in regulating macrophage M2 polarization. CONCLUSION: The piezoelectric Cs/Gel/PHA/PBT hydrogels developed here with favorable immunomodulation, angiogenesis, and osteogenesis functions may be used as a substitute in periosteum injuries, thereby offering the novel strategy of applying piezoelectric stimulation in bone tissue engineering for the enhancement of combat effectiveness in grassroots troops.

Metabolic and Transcriptional Stress Memory in Sorbus pohuashanensis Suspension Cells Induced by Yeast Extract.

Plant stress memory can provide the benefits of enhanced protection against additional stress exposure. Here, we aimed to explore the responses of recurrent and non-recurrent yeast extract (YE) stresses in Sorbus pohuashanensis suspension cells (SPSCs) at metabolomics and transcriptional levels. Biochemical analyses showed that the cell wall integrity and antioxidation capacity of SPSCs in the pretreated group were evidently improved. Metabolic analysis showed that there were 39 significantly altered metabolites in the pretreated group compared to the non-pretreated group. Based on the transcriptome analysis, 219 differentially expressed genes were obtained, which were highly enriched in plant-pathogen interaction, circadian rhythm-plant, oxidative phosphorylation, and phenylpropanoid biosynthesis. Furthermore, the correlation analysis of the transcriptome and metabolome data revealed that phenylpropanoid biosynthesis involved in the production of biphenyl phytoalexins may play a critical role in the memory response of SPSC to YE, and the key memory genes were also identified, including PAL1, BIS1, and BIS3. Collectively, the above results demonstrated that the memory responses of SPSC to YE were significant in almost all levels, which would be helpful for better understanding the adaptation mechanisms of medicinal plants in response to biotic stress, and laid a biotechnological foundation to accumulate favorable antimicrobial drug candidates from plant suspension cells.

High expression of NFAT2 contributes to carboplatin resistance in lung cancer.

Carboplatin is a platinum-based chemotherapy drug in lung cancer treatment. However, its efficacy is frequently limited by intrinsic and acquired drug resistance. Recently, nucleus factor of activated T cells, cytoplasmic 1 (NFAT2) has been recognized as an oncogene and involved in disease progression and drug resistance in various cancers. In the current study, we found that overexpression of NFAT2 was associated with poor prognosis in lung cancer patients, and is observed in a carboplatin resistant lung cancer cell line, indicative of its role in regulating drug response. We further showed that NFAT2 played a critical role in promoting cell proliferation and overcome carboplatin-induced DNA damage and cell cycle arrest. NFAT2 knockdown or inhibition of its nucleus translation via cyclosporine A largely restored the sensitivity to carboplatin in the resistant line by inducing DNA damage, blocking cell cycle progression and activating apoptotic cell death. We thus suggest that NFAT2 is a putative therapeutic target to overcome carboplatin resistance in lung cancers.

LCAL1 enhances lung cancer survival via inhibiting AMPK-related antitumor functions.

Lung cancer is one of the most common cancers and has been the most common cause of cancer deaths for several decades. Recently, lung cancer-associated lncRNA 1 (LCAL1) has been identified to be overexpressed in lung cancer tissues, while inhibiting LCAL1 expression has shown potential to inhibiting lung cancer growth. However, the molecular mechanism between LCAL1 and lung cancer cell survival remains poorly understood. In the present study, we provided the first evidence that LCAL1 may support lung cancer survival via inhibiting the activity of AMP-activated protein kinase (AMPK). According to our results, LCAL1 may physically interact with the catalytic subunit of tumor suppressor AMPK, prevent AMPK activation by upstream kinase (liver kinase B1), and thus inhibit the downstream AMPK signaling network. Our study revealed that overexpressed LCAL1 may induce aerobic glycolysis in lung cancer cells through AMPK/HIF1α axis, enhance protein synthesis through AMPK/mTOR/S6K axis, and suppress autophagic cell death through AMPK/ULK1 pathway. All these alterations supported rapid proliferation of lung cancer cells, while knockdown of LCAL1 expression demonstrated the potential of inhibiting lung cancer growth by reversing the tumorigenic phenotypes triggered by the loss of AMPK activity, and could become a promising therapeutic strategy for lung cancer treatment.

Prognostic role of the pre-treatment platelet-lymphocyte ratio in pancreatic cancer: a meta-analysis.

BACKGROUND AND AIMS: Recently, the pre-treatment platelet-lymphocyte ratio (PLR), which is based on blood parameters, was accepted as a prognostic factor for patients with various cancers. Numerous studies have investigated the prognostic role of the PLR in pancreatic cancer; however, it remains unclear. Therefore, we conducted this meta-analysis to evaluate the relationship between the pre-treatment PLR and overall survival (OS) in pancreatic cancer. MATERIALS AND METHODS: We performed a systematic literature search of the PubMed, Embase and Web of Science databases for relevant studies that explored the prognostic role of the pre-treatment PLR in pancreatic cancer. The hazard ratios (HRs) and 95% confidence intervals (CIs) related to OS were pooled using a random effects model. RESULTS: Fourteen retrospective cohort studies involving 2,260 patients were included in this meta-analysis. Compared with low PLR, high PLR was a predictor of shorter OS (HR = 1.24, 95% CI: 1.10-1.39, I2 = 74%). CONCLUSIONS: In this meta-analysis, high pre-treatment PLR was a bio-predictor of short OS in patients with pancreatic cancer, suggesting that PLR could be used to predict prognosis of patients with pancreatic cancer before treatment. However, additional well-designed and large-scale studies are necessary.

[Intestinal absorption and metabolism of Puerariae Lobatae Radix decoction by in situ closed-loop method].

Biopharmaceutics classification system of Chinese materia medica (CMMBCS) emphasizes characteristic of the multi-component environment based on the drug solubility and permeability. In this study, the in situ closed-loop method combined with LC-MS technique was utilized to study the intestinal absorption and metabolism of Puerariae Lobatae Radix decoction (PLRD), providing selection basis for intestinal permeability components in CMMBCS. A total of 36 components were identified from PLRD. Among them, 17 components could be detected in the plasma sample, indicating that 17 components could be absorbed into blood, so these 17 components could be used as intestinal permeability evaluation components in CMMBCS. The other 19 components were not detected in the plasma sample, suggesting that they may not be absorbed or metabolized by the gut wall enzymes.

[Absorption and metabolism of Chuanxiong Rhizoma decoction with multi-component sequential metabolism method].

The multiple components in Chinese herbal medicines (CHMS) will experience complex absorption and metabolism before entering the blood system. Previous studies often lay emphasis on the components in blood. However, the dynamic and sequential absorption and metabolism process following multi-component oral administration has not been studied. In this study, the in situ closed-loop method combined with LC-MS techniques were employed to study the sequential process of Chuanxiong Rhizoma decoction (RCD). A total of 14 major components were identified in RCD. Among them, ferulic acid, senkyunolide J, senkyunolide I, senkyunolide F, senkyunolide G, and butylidenephthalide were detected in all of the samples, indicating that the six components could be absorbed into blood in prototype. Butylphthalide, E-ligustilide, Z-ligustilide, cnidilide, senkyunolide A and senkyunolide Q were not detected in all the samples, suggesting that the six components may not be absorbed or metabolized before entering the hepatic portal vein. Senkyunolide H could be metabolized by the liver, while senkyunolide M could be metabolized by both liver and intestinal flora. This study clearly demonstrated the changes in the absorption and metabolism process following multi-component oral administration of RCD, so as to convert the static multi-component absorption process into a comprehensive dynamic and continuous absorption and metabolism process.

Left atrial endocardial dysfunction and platelet activation in patients with atrial fibrillation and mitral stenosis.

OBJECTIVE: This study demonstrated left atrial endocardial dysfunction and platelet activation in patients with atrial fibrillation and mitral stenosis. METHODS: Study included 80 patients with mitral stenosis and atrial fibrillation (40 each with and without left atrial thrombosis), 15 healthy volunteers, and 10 left atrial appendage (LAA) specimens from donor hearts. Blood samples were collected through peripheral vein and left atrium, with peripheral blood samples of volunteers as controls. LAA specimens were collected during operations. LAA expressions of von Willebrand factor (vWF) and P-selectin were determined immunohistochemically; plasma concentrations were measured by enzyme-linked immunosorbent assay. LAA expressions of vWF and P-selectin genes in were quantitated with real-time fluorescent quantitative polymerase chain reaction. RESULTS: The difference in vWF and P-selectin plasma levels between left atrial and peripheral venous blood was not significant; however, peripheral plasma levels of vWF and P-selectin were significantly higher in those with thrombosis than without thrombosis, which in turn were higher than in healthy subjects. Both vWF and P-selectin proteins were stained in both left atrial endocardium and cardiomyocytes. The normalized vWF gene expression relative to control was 3.04 in patients with thrombosis and 2.16 in those without thrombosis (P<.01). The difference in P-selectin gene expressions among the groups was not significant. CONCLUSIONS: No differences were observed in plasma levels of vWF and P-selectin between left atrial and peripheral venous blood. Over expression of vWF gene in LAA may contribute to increased plasma vWF levels. P-selectin and vWF together may play a role in thrombosis.

Modulation effects of cordycepin on the skeletal muscle contraction of toad gastrocnemius muscle.

Isolated toad gastrocnemius muscle is a typical skeletal muscle tissue that is frequently used to study the motor system because it is an important component of the motor system. This study investigates the effects of cordycepin on the skeletal muscle contractile function of isolated toad gastrocnemius muscles by electrical field stimulation. Results showed that cordycepin (20 mg/l to 100 mg/l) significantly decreased the contractile responses in a concentration-dependent manner. Cordycepin (50 mg/l) also produced a rightward shift of the contractile amplitude-stimulation intensity relationship, as indicated by the increases in the threshold stimulation intensity and the saturation stimulation intensity. However, the most notable result was that the maximum amplitude of the muscle contractile force was significantly increased under cordycepin application (122±3.4% of control). This result suggests that the skeletal muscle contractile function and muscle physical fitness to the external stimulation were improved by the decreased response sensitivity in the presence of cordycepin. Moreover, cordycepin also prevented the repetitive stimulation-induced decrease in muscle contractile force and increased the recovery amplitude and recovery ratio of muscle contraction. However, these anti-fatigue effects of cordycepin on muscle contraction during long-lasting muscle activity were absent in Ca2+-free medium or in the presence of all Ca2+ channels blocker (0.4 mM CdCl2). These results suggest that cordycepin can positively affect muscle performance and provide ergogenic and prophylactic benefits in decreasing skeletal muscle fatigue. The mechanisms involving excitation-coupled Ca2+ influxes are strongly recommended.

Preparation and characterization of bionanocomposite fiber based on cellulose and nano-SiO2 using ionic liquid.

Microcrystalline cellulose (MCC)/nano-SiO2 composite fibers were processed from solutions in 1-allyl-3-methylimidazolium chloride (AMIMCl) by the method of dry-jet wet spinning. The oscillatory shear measurements demonstrated that the gel network formed above 10 wt% nano-SiO2 and the complex viscosity increased with increasing nano-SiO2. Remarkably, the shear viscosity of the nanofluids was even lower than solutions without nano-SiO2 under high shear rates. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images revealed that well-dispersed particles exhibit strong interfacial interactions with cellulose matrix. Measurements on wide-angle X-ray diffraction (WAXD) indicated that the regenerated cellulose and nanocomposite fibers were the typical cellulose II crystalline form, which was different from the native cellulose with the polymorph of Type I. The tensile strength of the nanocomposite fibers was larger than that of pure cellulose fiber and showed a tendency to increase and then decrease with increasing nano-SiO2. Furthermore, the nanocomposite fibers exhibited improved thermal stability.

Metronomic chemotherapy in combination with antiangiogenic treatment induces mosaic vascular reduction and tumor growth inhibition in hepatocellular carcinoma xenografts.

BACKGROUND: In addition to sprouting angiogenesis, other mechanisms, such as mosaic tumor vessel formation, have been recognized to contribute to tumor vascularization. We sought to examine vascular alteration as well as tumor growth inhibition after treatment with antiangiogenic therapy, chemotherapy alone or in combination. METHODS: Hepatocellular carcinoma cells (Hep3B) expressed green fluorescent protein were utilized to establish orthotopic xenograft model in nude mice. The formation and distribution of mosaic vessels was analyzed quantitatively by immunolabeling. Next, changes in tumor microcirculation and therapeutic effects on tumor growth were evaluated in several different treatment groups: control, conventional doxorubicin, metronomic doxorubicin, bevacizumab, bevacizumab plus conventional doxorubicin, and bevacizumab plus metronomic doxorubicin. In addition, we examined the effects of combined regimens on lung metastasis using a highly metastatic human hepatocellular carcinoma (HCCLM3) mouse model. RESULTS: Approximately 62 % of the vessels were present in the central part or near the midsection of the tumor and were mosaic. Only the combined antiangiogenic treatment and chemotherapy (metronomic schedule, P = 0.00; conventional schedule, P = 0.02) had a significant effect on the degree of mosaic vasculature. Metronomic doxorubicin in combination with bevacizumab had an even more profound effect than bevacizumab plus conventional doxorubicin (P < 0.05) on tumor growth inhibition and survival. However, bevacizumab plus metronomic doxorubicin failed to inhibit lung metastasis compared with antiangiogenic monotherapy. CONCLUSIONS: Metronomic chemotherapy in combination with antiangiogenic treatment results in the reduction of mosaic tumor vasculature, inhibition of tumor growth, and enhanced survival of mice. Further investigation of drug scheduling is required to optimize antitumor activity.

Surgical management of persistent left superior vena cava associated with an absent right superior vena cava.

A case of persistent left with absent right superior vena cava accompanied with atrial septal defect in a six-year-old girl is presented. This rare venous malformation was diagnosed incidentally during surgery when the pericardium was incised. An L-shape cannula was directly inserted into the left superior vena cava for cardiopulmonary bypass. The atrial septal defect was closed with a fresh autologous pericardial patch. The surgical management of this rare anomaly is the subject of this review.

Intercostal artery aneurysm associated with coarctation of aorta in an adult.

Intercostal artery aneurysms associated with coarctation of aorta (CoA) are rare and their natural histories are poorly understood. This report describes the surgical correction of this anomaly in an adult without performing extracorporeal circulation. The coarctated segment of aorta and intercostal artery aneurysm were resected, and the continuity of the descending aorta was reestablished with an interposed vascular graft.

Probing charged impurities in suspended graphene using Raman spectroscopy.

Charged impurity (CI) scattering is one of the dominant factors that affects the carrier mobility in graphene. In this paper, we use Raman spectroscopy to probe the charged impurities in suspended graphene. We find that the 2D band intensity is very sensitive to the CI concentration in graphene, while the G band intensity is not affected. The intensity ratio between the 2D and G bands, I(2D)/I(G), of suspended graphene is much stronger compared to that of nonsuspended graphene, due to the extremely low CI concentration in the former. This finding is consistent with the ultrahigh carrier mobility in suspended graphene observed in recent transport measurements. Our results also suggest that at low CI concentrations that are critical for device applications, the I(2D)/I(G) ratio is a better criterion in selecting high quality single layer graphene samples than is the G band blue shift.

[Short-term results of audiological change of nasopharyngeal carcinoma patient after radiotherapy and chemotherapy].

OBJECTIVE: To investigate short-stage results of audiological change of nasopharyngeal carcinoma patients after radiotherapy and chemotherapy treatment. METHODS: According to treatment modus of nasopharyngeal carcinoma, 64 cases (128 ears) patients were divided to simple radiotherapy group (45 cases, 90 ears) and radiotherapy with chemotherapy group (combination treatment group, 19 cases, 38 ears). Meanwhile, 25 cases (50 ears) people took as control group, who had no obviously ear and nose disease. About two or three months after radiotherapy and chemotherapy treatment completion, three groups were detected by otoscopy, pure tone test, tympanogram and eustachian tube function, respectively. Then, hearing variation of all patients after radiotherapy and chemotherapy treatment were investigated and compared each other. At the same time, the character and level of audiological change were also analyzed. RESULTS: Eardrum character of nasopharyngeal carcinoma patients appeared change after radiotherapy. Simple radiotherapy and combination treatment groups were found having hearing impairment and eustachian tube functional disturbance. Moreover, most patients of simple radiotherapy group showed conductive deaf (24%, 22/90), and combination treatment group exhibited mingle (24%, 9/38) or sensorineural deafness (29%, 11/38). CONCLUSIONS: Recent hearing of nasopharyngeal carcinoma patients were damaged by radiotherapy and chemotherapy treatment, radiotherapy treatment induced middle ear or eustachian tube function disturbance, chemotherapy treatment had cochleotoxicity, compared with other treatment, combination treatment was more aggravated hearing impairment.

[Effects of gantry position on the accuracy of lead block localization and relative quality control methods].

BACKGROUND & OBJECTIVE: To date, the low-melting point lead blocks are commonly used as a beam modifier for the accurate three-dimensional (3D) radiotherapy in China. However, care should be taken when using blocks even though they are verified on the specified simulator or linear accelerator before treatment. This is because that those verifications are only performed under the gantry angle of 0 degree. For the oblique gantry angles, the block may shift in the tray leading to the positioning error. In this study, we explored the influence of gantry position on the accuracy of lead block localization, and the relative quality control methods were also provided. METHODS: After rotating the gantry to 90 degrees and setting the collimator angle to 0 degree on a Siemens linear accelerator, a crosshair was marked on the plastic base of the lead block fitted to the tray according to the crosshair of light field of the linear accelerator. Then the discrepancy between the base crosshair and the light crosshair was investigated for different gantry positions and collimator angles. RESULTS: There was clearance between the plastic base of the lead block and the block tray. As for some collimator angles at oblique gantry positions, the lead block shifted in the tray due to the gravity. This led to the position error of blocked radiation fields from 0 up to 3.6 mm at the isocenter plane. CONCLUSIONS: Accurately marking the crosshair on the plastic base of the lead block is an effective method of correctly fixing the lead block influenced by the plastic base as well as of double checking the accuracy of the localization of the lead block. The positioning error of oblique gantry positions can be minimized by limiting the collimator to some degrees which makes the block tray opening to the ceiling or parallel to the ground while the bisector of the restrictive angle points slanting to the ceiling (that is, the first baseline of the block tray points inclined or right to the ceiling).