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Background In allogeneic-hematopoietic stem cell transplantation for acute myeloid leukemia (AML), donor T cells combat leukemia through the graft-versus-leukemia (GVL) effect, while they also pose a risk of triggering life-threatening graft-versus-host disease (GVHD) by interacting with recipient cells. The onset of GVHD hinges on the interplay between donor T cells and recipient antigen-presenting cells (APCs), sparking T-cell activation. However, effective methods to balance GVHD and GVL are lacking.Methods In our study, we crafted nanocapsules by layering polycationic aminated gelatin and polyanionic alginate onto the surface of T cells, examining potential alterations in their fundamental physiological functions. Subsequently, we established an AML mouse model and treated it with transplantation of bone marrow cells (BMCs) combined with encapsulated T cells to investigate the GVL and anti-GVHD effects of encapsulated T cells. In vitro co-culture was employed to probe the effects of encapsulation on immune synapses, co-stimulatory molecules, and tumor-killing pathways.Results Transplantation of BMCs combined with donor T cells selectively encapsulated onto AML mice significantly alleviates GVHD symptoms while preserving essential GVL effects. Encapsulated T cells exerted their immunomodulatory effects by impeding the formation of immune synapses with recipient APCs, thereby downregulating co-stimulatory signals such as CD28-CD80, ICOS-ICOSL, and CD40L-CD40. Recipient mice receiving encapsulated T-cell transplantation exhibited a marked increase in donor Ly-5.1-BMC cell numbers, accompanied by unaltered in vivo expression levels of perforin and granzyme B. While transient inhibition of donor T-cell cytotoxicity in the tumor microenvironment was observed in vitro following single-cell nanoencapsulation, subsequent restoration to normal antitumor activity ensued, attributed to selective permeability of encapsulated vesicle shells and material degradation. Moreover, the expression of apoptotic proteins and FAS-FAS ligand pathway at normal levels was still observed in leukemia tumor cells.Conclusions Encapsulated donor T cells effectively mitigate GVHD while preserving the GVL effect by minimizing co-stimulatory signaling with APCs through early immune isolation. Subsequent degradation of nanocapsules restores T-cell cytotoxic efficacy against AML cells, mediated by cytotoxic pathways. Using transplant-encapsulated T cells offers a promising strategy to suppress GVHD while preserving the GVL effect.

Micro- and nano-bubble jet stirring, as an emerging technology, shows great potential in complex mineral sorting. Flow field characteristics and structural parameters of the gas–liquid two-phase system can lead to uneven bubble distribution inside the reaction vessel. Gas–liquid mixing uniformity is crucial for evaluating stirring effects, as increasing the contact area enhances reaction efficiency. To improve flotation process efficiency and resource recovery, further investigation into flow field characteristics and structural optimization is necessary. The internal flow field of the jet-stirred tank was analyzed using computational fluid dynamics (CFDs) with the Eulerian multiphase flow model and the Renormalization Group (RNG) k − ε turbulence model. Various operating (feeding and aerating volumes) and structural parameters (nozzle direction, height, inner diameter, and radius ratio) were simulated. Dimensionless variance is a statistical metric used to assess gas–liquid mixing uniformity. The results indicated bubbles accumulated in the middle of the vessel, leading to uneven mixing. Lower velocities resulted in low gas volume fractions, while excessively high velocities increased differences between the center and near-wall regions. Optimal mixing uniformity was achieved with a circumferential nozzle direction, 80 mm height, 5.0 mm inner diameter, and 0.55 radius ratio.

Abstract Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Ethanol consumption has been reported to reduce morbidity in RA patients, but the mechanism behind it remains unclear. Our results showed that Muribaculaceae was predominant in the gut microbiota of mice after ethanol treatment, and the levels of microbiota metabolite acetate were increased. Acetate reduced arthritis severity in collagen-induced arthritis (CIA) mice, which was associated with a decrease in the articular neutrophils and the myeloperoxidase-deoxyribonucleic acid complex in serum. Meanwhile, in vitro experiments confirmed that acetate affected neutrophil activity by acting on G-protein-coupled receptor 43, which reduced endoplasmic reticulum stress in neutrophils and inhibited neutrophil extracellular traps formation. Furthermore, exogenous acetate reversed CIA mice with exacerbated gut microbial disruption, further confirming that the effect of gut microbial metabolite acetate on neutrophils in vivo is crucial for the immune regulation. Our findings illuminate the metabolic and cellular mechanisms of the gut-joint axis in the regulation of autoimmune arthritis, and may offer alternative avenues to replicate or induce the joint-protective benefits of ethanol without associated detrimental effects.

The cable room, located at the base of the ring main unit, is prone to water vapor due to its proximity to damp cable holes and its relatively enclosed structure. This may penetrate internally and ultimately affect operational safety. Therefore, a dehumidifier was introduced to utilize dry air for internal circulation. To enhance the dehumidification in the cable room, the cable room device was designed for experimental research. Meanwhile, computational fluid dynamics (CFD)-electromagnetic (EMAG) coupling simulation is used to calculate the power loss of heat sources and their influence on multiple physical fields in numerical simulations. The feasibility of this study was confirmed by comparing the relative humidity, temperature, and velocity values between the experimental and numerical approaches. Furthermore, the layout of the ventilation pipes was modified to a vertical distribution, with upward supply and downward suction, to improve the airflow. The results indicate that the maximum relative errors in temperature, relative humidity, and velocity are only 3.61%, 7.14%, and 7.14%, respectively, which fall within an acceptable range. On this basis, additional simulation analysis was conducted on the humidity, dew point temperature, and airflow within the cable room, using an optimized model with a more comprehensive internal structure and cables. After implementing an optimized ventilation pipe layout, the relative humidity at the corresponding measuring points can decrease by up to 10.6%. The dew point temperature has decreased by 2.61 °C and the airflow has become more stable.

Abstract Intelligent and coordinated unmanned aerial vehicle (UAV) swarm combat will be the main mode of warfare in the future, and mechanistic design of autonomous cooperation within swarms is the key to enhancing combat effectiveness. Exploration of the essential features and patterns of autonomous collaboration in unmanned swarms has become the focus of scientific research and technological applications, in keeping with the evolving conceptions of the military theatre. However, given the unique attributes of the military and the novelty of the warfare mode of unmanned swarms, few achievements have been reported in the existing research. In this study, we analysed the military requirements of unmanned swarm operations and proposed an analytic framework for autonomous collaboration. Then, a literature review addressing swarm evolution dynamics, game-based swarm collaboration, and collaborative evolution on complex networks was conducted. Next, on the basis of the above work, we designed a community network for unmanned swarm cooperation and constructed a collaborative evolution model based on the multiplayer public goods game (PGG). Furthermore, according to the “network” and “model”, the dynamic evolution process of swarm collaboration was formally deduced. Finally, a simulation was conducted to analyse the influence of relevant parameters (i.e., swarm size, degree distribution, cost, multiplication factor) on the collaborative behaviour of unmanned swarms. According to the simulation results, some reasonable suggestions for collaborative management and control in swarm operation are given, which can provide theoretical reference and decision-making support for the design of coordination mechanisms and improved combat effectiveness in unmanned swarm operation.

With the constant development of power, information and other technologies, the advantages of unmanned ships are emerging in anti-mine, anti-submarine, electronic warfare, maritime security, maritime interception, and other military fields. This paper describes the development of unmanned ships and power technology and clarifies that the integrated power system has become a major trend of medium and large-sized unmanned ships. It also introduces the application of integrated power system in manned and unmanned platforms, and proposes that issues like size, weight, and control of vibration and noise are of essential for the integrated power system for unmanned platforms. In the end, this paper summarizes the trend of integrated power technology for unmanned platforms and identifies the key scientific problems of integrated power technology on unmanned platform, namely the intelligent operation of integrated power system, high-performance motor materials, information perception of complex motor system, power electronic device and system, high-performance power conversion and efficient energy storage.

Abstract Background Generic medicines substitution is an important means to control rapid growth of pharmaceutical expenditures for the healthcare system in China. Acceptance and utilization of generic medicines is highly influenced by healthcare providers’ perceptions. This study aimed to compare the knowledge, awareness and perceptions of generic medicines between physicians and pharmacists in China. Methods We used an online, cross-sectional survey across China. The questionnaire explored four sections: demographic characteristics, assessment of the participants’ knowledge and awareness of generic medicines, perceptions of generic medicines and generic substitution practices. Chi-square or Mann–Whitney-U tests were applied to compare differences between physicians and pharmacists. P-values

Background: Individualized pharmaceutical care, which consists of therapeutic drug monitoring (TDM), pharmacogenetic (PGx) testing and pharmacist-managed clinic (PMC), is one of the most important trends in clinical pharmacy development in the future. While relevant studies in China were primarily single-center or regional. This study aims to explore the current status of individualized pharmaceutical care in China, find out the existing problems and provide references for its further development.Methods: An electronic questionnaire was used and national hospitals’ pharmaceutical administration data from January to December 2019 were collected. The data were sorted into Excel for further statistical analysis. All analyses were descriptive.Results: The proportions of hospitals that performed TDM and PGx testing were 12.83% and 9.48%, respectively. The major responsible departments were the clinical laboratory and pharmacy department. External quality control was carried out in around 70% of hospitals for both TDM and PGx testing. More than half of hospitals provided TDM services for valproate sodium, digoxin, carbamazepine, vancomycin and cyclosporine. And an average of 6.84 drugs were performed TDM in 540 hospitals. Clopidogrel and warfarin were the top two drugs that performed PGx testing. As for the PMC, 10.03% of hospitals opened PMC, of which 60.00% had independent PMC. Approximately 80% of PMC services were free of charge.Conclusion: The development of individualized pharmaceutical care in China is still in the early stage. Different sectors have to coalesce to promote its implementation, including the appropriate education, coverage, reimbursement policies, high-quality evidence, data systems, health system processes and health policies, etc.

This current case report describes a 56-year-old male patient with a skin mass on his lip that had been growing for 1 year. The pathological findings demonstrated that the epidermis was characterized by hyperkeratosis, hyperplasia and hypertrophy and was formed in the shape of a crater. The skin on both ends had developed into a ball-like growth that resembled a volcanic cone. There was invasive growth of heterotype squamous epithelium and a small number of inflammatory cells infiltrating the dermis. Immunohistochemistry demonstrated an increase in P16 (the focus, +) and the hot spot Ki-67 index. The diagnosis was of tumour-like hyperplasia, malignancy and moderate-to-severe dysplasia confirming that it was keratoacanthoma. The patient underwent surgical resection and was discharged from hospital, but the tumour returned. Paclitaxel and cisplatin were administered intraoperatively and bilateral lingual artery perfusion chemoembolization was undertaken six times. This procedure led to an excellent postoperative recovery and discharge from hospital. Tumour therapy was regarded as successful. The patient’s medical history included acute lymphoblastic leukaemia L1 and long-term immunosuppressant use. After a 6-month period of follow-up, he died from systemic organ failure as a consequence of having too many ailments.

Smart classrooms are a relatively confined public space for college students. SARS-COV-2 and other respiratory viruses have been shown to pose a more significant threat to human health in relatively confined spaces. Using numerical simulation method to simulate the transmission and concentration distribution of virus-carrying droplets in smart classrooms in three different seasons (summer, winter, transitional seasons: spring and autumn). The Realizable k-ε model is used to simulate the airflow pattern in the smart classroom, and the Lagrangian method is used to simulate the transmission of droplets. The transmission process of droplets produced from the teacher standing on the platform and the student sitting on the seat is studied. The influence of three kinds of outdoor temperature on droplet transmission and the body deposition fraction of people in the smart classroom is analyzed. The results show that droplet transmission speed is maximum at the temperature of 5 degrees when the outdoor temperature is 5 °C, 20 °C, and 35 °C respectively. At 10 s, the transmission distance of droplets increases by 9.55% compared with that at 20 °C and 10.31% compared with that at 35 °C. In addition, the body deposition fraction is also affected by the location of the vent, with downwind contact being 6 times more likely than upwind contact. The research results can provide suggestions and measures for epidemic prevention and control in smart classrooms.

Perivascular epithelioid cell tumors (PEComas) are extremely rare mesenchymal neoplasms for which the uterus is the most common site. The prognosis of malignant PEComa is poor as it is characterized by resistance to classical chemotherapies. Both mTOR inhibitors and VEGFR inhibitors exhibited clinical utility in treating malignant PEComas, but the combination of these two regimens has rarely been reported. In the present case, a uterine PEComa patient developed lung and bone metastases after the failure of chemotherapies and derived benefit from the combination regimen of an mTOR inhibitor (everolimus) and a VEGFR inhibitor (apatinib), achieving a 15-month progression-free survival. Targeted NGS revealed TP53 and TSC2 mutations in the patient’s primary uterine tumors and plasma ctDNA at disease progression. Plasma ctDNA clearance was consistent with a radiologic partial response determined by RECIST 1.1 and a reduction of neuron-specific enolase (NSE) and cancer antigen 125 (CA125) levels. Thus, we provided clinical evidence supporting the administration of combined therapy of mTOR and VEGFR inhibitors to metastatic uterine PEComa patients and highlighted the application of serial plasma ctDNA profiling for dynamic disease monitoring.

Mitotane is the only drug approved to treat adrenocortical carcinoma (ACC), and a relationship of pharmacokinetic/pharmacodynamic has been characterized. However, limited evidence concerning affecting factors in large interindividual variability of the pharmacokinetics of mitotane is available. To address this question, a retrospective analysis was performed on ACC Chinese patients treated with mitotane for more than 3 months. Mitotane plasma trough concentrations were detected at the steady state, and CYP2B6, CYP3A4, and pregnane X receptor (PXR) polymorphisms were genotyped. After examining homogeneous pharmacologic data, we restricted the analyses to 36 patients that received mitotane for a median (interquartile range, IQR) of 9 months (5.00–22.50) with a median dose of 2 g/day (2.00–2.50). As a result, drug exposure was significantly influenced by the cumulative dose of mitotane, and CYP2B6 516GG and CYP2B6 26570CC were at high risk to be below the therapeutic range of mitotane. No association was found between mitotane concentrations with CYP3A4 or PXR polymorphism. Our data firstly indicated that the cumulative dose of mitotane and polymorphisms of CYP2B6 516 and CYP2B6 26570 might significantly affect mitotane plasma trough concentrations in Chinese ACC patients.

Abstract Backgrounds Although kidney impairments have been reported following immune checkpoint inhibitors (ICIs) in clinical studies, there are few pharmacoepidemiology studies to compare the occurrences, clinical features, and prognosis of renal adverse effects. Methods Disproportionality and Bayesian analysis were used in data mining to screen the suspected renal adverse effects after the administration of different ICIs, based on FDA's Adverse Event Reporting System (FAERS) from January 2004 to September 2019. The time to onset, fatality and hospitalization rates of renal adverse effects were also investigated. Results We identified 1444 reports of renal adverse effects. Affected patients tended to be older than 65 years (52.7%). Renal effects were most commonly reported in nivolumab monotherapy (33.24%). Atezolizumab appeared the strongest association among six ICI monotherapies, based on the highest reporting odds ratio (ROR = 144.38, two‐sided 95% CI = 123.08 −169.37), proportional reporting ratio (PRR = 139.13, χ2 = 21 425.38), and empirical Bayes geometric mean (EBGM = 131.75, one‐sided 95% CI = 115.28). The combination treatments showed higher RORs, PRRs, and EBGMs, compared with either nivolumab or pembrolizumab monotherapy. The median onset time of renal adverse effects was 48 (interquartile range [IQR] 18.75‐121.25) days after the monotherapies of ICI regimens. Patients treated with the combination of nivolumab plus ipilimumab were younger than receivers in nivolumab monotherapy (63.81 ± 12.03 vs 66.39 ± 11.53, P = .004); The fatality rate of renal adverse effects appeared lower in the combination group, compared to nivolumab monotherapy (18.53% vs 27.50%, P = .004). The top hospitalization rates due to renal effects occurred in patients with combination therapies. Conclusion Based on the FAERS database, we profiled renal adverse effects after various ICIs with real‐world data in occurrences, clinical characteristics, and prognosis. Renal effects should be tightly monitored, especially within the first several months after ICIs administration. Particular concern should be paid for patients with a tendency for kidney impairments, such as old age.

Abstract Background Rivaroxaban, a novel oral anticoagulant drug, is widely used in clinical practice. There is no standardized laboratory monitoring for rivaroxaban, and its plasma concentration in Chinese patients with deep vein thrombosis is unclear. The rivaroxaban concentrations in human plasma and determine the steady-state concentration of rivaroxaban in patients with deep vein thrombosis are needed. Methods An ultra-high-performance liquid chromatography with mass spectrometric detection method was developed. Chromatographic separation was performed on a Waters BEH C18 column with isocratic elution using a mobile phase composed of acetonitrile and water. Quantitation of the analytes was performed using positive ionization mode and mass transitions of m/z 437.3 → m/z 145.0 and m/z 440.1 → m/z 145.0 for rivaroxaban and the internal standard, respectively. Blood samples were collected at 0 h and 2 h after patients took rivaroxaban for 7 days or more. Results The method was validated over the concentration range of 0.5 ~ 400 ng•mL− 1 with a very low limit of quantification of 0.5 ng·mL− 1, and the intra- and inter-day precision (RSD%) were

Introduction: Immune checkpoint inhibitors (ICIs) have substantially improved the clinical outcomes of various malignancies. However, the adverse event of tumor lysis syndrome (TLS) has not been included in the National Comprehensive Cancer Network guidelines or drug inserts. In this study, we aimed to establish the relationship between ICI therapies and TLS events using data from a real-world pharmacovigilance database.Methods: The MedDRA terms of TLS and both generic and brand names of ICIs were retrieved from the FDA Adverse Event Reporting System. Four frequentist algorithms were employed to confirm the association between the TLS and the ICI regimens, involving anti-cytotoxic T lymphocyte antigen-4 (anti-CTLA-4), anti–programmed death receptor-1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1), and anti-(CTLA-4 + PD-1). A descriptive and statistical analysis was performed according to the case information.Results: One hundred sixty-four TLS cases, where patients underwent anti-CTLA-4 (n = 14), anti-(PD-1)/(PD-L1) (n = 113), or anti-(CTLA-4 + PD-1) (n = 37) therapies, were collected between the first quarter of 2004 and the fourth quarter of 2020. The most coverage-reporting year, age-group, sex, reporter, region, country, and indication were 2020 (n = 62), 60–74 years (n = 65), males (n = 105), physician (n = 66), Asia (n = 80), Japan (n = 67), and lung and thymus malignancies (n = 40), respectively. The median TLS onset time associated with anti-CTLA-4, anti-(PD-1)/(PD-L1), and anti-(CTLA-4 + PD-1) therapies was 6 (IQR: 2–39.5), 9 (IQR: 2–40), and 20 (IQR: 7.5–37.75) days, respectively. Mortality distribution of 71 reported death outcomes among three groups was statistically significant. All four algorithm signal values of anti-(CTLA-4 + PD-1) were higher than those of anti-CTLA-4 and anti-(PD-1)/(PD-L1).Conclusion: Elderly male patients with lung and thymus malignancies are frequently predisposed to TLS. ICI therapies could induce TLS in both solid and hematological malignancies. The rapid onset time and poor outcomes of patients prompt caution from health-care professionals.

Liver fibrosis, a chronic damage process related to further progression of hepatic cirrhosis, has yet no truly effective treatment. Isochlorogenic acid A (ICQA), isolated from a traditional Chinese herbal medicine named Laggera alata (DC.) Sch.Bip. ex Oliv. (Asteraceae), is proved to exhibit anti-inflammatory, hepatoprotective and antiviral properties. However, the actions of ICQA on liver fibrosis are poorly understood. The purpose of this study was to evaluate the actions of ICQA on liver fibrosis and clarify the underlying mechanism. It was found that ICQA had significant protective actions on liver injury, inflammation as we as fibrosis in rats. Meanwhile, ICQA prevented hepatic stellate cells (HSC) activation, indicated by its inhibitory effect on the overexpression of α-smooth muscle actin (α-SMA). In addition, the reduced fibrosis was found to be associated with the decreased protein expression of high-mobility group box 1 (HMGB1) as well as toll like receptor (TLR) 4. Simultaneously, ICQA can suppress the cytoplasmic translocation of HMGB1 in rat liver. Further investigations indicated that ICQA treatment dramatically attenuated the nuclear translocation of the nuclear factor-kB (NF-κB) p65 and suppressed the hepatic expression of p−IκBα in rats with liver fibrosis. Taken together, our study indicated that ICQA could protect against CCl4-induced liver fibrosis probably through suppressing the HMGB1/TLR4/NF-κB signaling pathways.

ObjectiveTo explore the role of B cells in rheumatoid arthritis (RA) and the potential effects and mechanisms of etanercept on B cells.MethodsIn RA patients, the levels of tumor necrosis factor-α (TNF-α) and B cell activating factor (BAFF) were detected by ELISA. The percentage of B cell subsets was measured by flow cytometry. Laboratory indicators (rheumatoid factor, C-reactive protein, erythrocyte sedimentation rate) and clinical indicators (disease activity score in 28 joints, health assessment questionnaire score, swollen joint counts, tender joint counts) were measured. The correlation between B cell subsets and laboratory indicators or clinical indicators was analyzed. In mice, B cells proliferation was detected by CCK-8 kit. The expression of TNFRII and the percentage of B cell subsets in spleen were detected by flow cytometry. The expressions of TRAF2, p38, P-p38, p65, P-p65 in B cells were detected by WB.ResultsThe percentage of CD19−CD27+CD138+ plasma B cells was positively correlated with ESR or RF. Etanercept could decrease the percentage of CD19+ total B cells, CD19+CD27+ memory B cells and CD19−CD27+CD138+ plasma B cells, reduce the levels of TNF-α, BAFF, relieve clinical and laboratory indicators in RA patients. In addition, etanercept could inhibit the proliferation of B cells, bate the differentiation of transitional B cells to mature B cells, down-regulate the expression of TNFRII, TRAF2, P-p38, P-p65 in B cells.ConclusionB cells act a key role in the pathogenesis of RA. Etanercept inhibits B cells differentiation by down-regulating TNFRII/TRAF2/NF-κB signaling pathway.

Background. The U.S. Food and Drug Administration (FDA) released a safety warning of Fournier gangrene (FG), a rare but serious adverse effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors in August 2018. However, existing studies have focused mainly on individual FG case reports. Although several previous studies conducted reviews of cases, objective scientific analysis was not applied, and the prognosis data were inadequate. Objective. This study is aimed at presenting data supplementary to existing studies by analysing postmarketing adverse event reports in the FDA Adverse Events Reporting System (FAERS) database. Multiple statistical analysis methods were applied to evaluate the potential association between SGLT2 inhibitors and FG, thus providing reliable and professionalized medication usage recommendations for SGLT2 inhibitors in clinical practice. Methods. Disproportionality analysis and Bayesian analysis were applied for data mining among the suspected adverse event reports of FG associated with SGLT2 inhibitors recorded in the FAERS database during the period from January 2004 to September 2019. Results. There were 542 FG cases identified in the FAERS database in patients receiving SGLT2 inhibitors. Among all SGLT2 inhibitor therapies, empagliflozin was associated with the highest number of FG reports (232 in total), while empagliflozin plus metformin had the strongest association with FG occurrence with the reporting odds ratio (ROR 54.79, 95% two-sided CI 31.56 to 95.12) and proportional reporting ratio (PRR 53.36, χ2 666.70). There were 391 patients who underwent initial or prolonged hospitalization (72.14%), and 26 patients died (4.81%). Three new FG cases caused by ertugliflozin were found in 2019. Conclusion. The analysis of SGLT2 inhibitor-associated FG reports in the FAERS database identified signals between the drug and adverse events of interest. It also provides comprehensive information on the characteristics of FG onset and prognosis. Clinicians should pay more attention to this rare but severe adverse event when prescribing SGLT2 inhibitors in clinical practice.

Collagen triple helix repeat containing-1 (CTHRC1) has been identified as cancer-related protein. CTHRC1 expresses mainly in adventitial fibroblasts and neointimal smooth muscle cells of balloon-injured vessels and promotes cell migration and tissue repair in response to injury. CTHRC1 plays a pivotal role in some pathophysiological processes, including increasing bone mass, preventing myelination, and reversing collagen synthesis in many tumor cells. The ascended expression of CTHRC1 is related to tumorigenesis, proliferation, invasion, and metastasis in various human malignancies, including gastric cancer, pancreatic cancer, hepatocellular carcinoma, keloid, breast cancer, colorectal cancer, epithelial ovarian cancer, esophageal squamous cell carcinoma, cervical cancer, non-small-cell lung carcinoma, and melanoma. And molecules that regulate the expression of CTHRC1 include miRNAs, lncRNAs, WAIF1, and DPAGT1. Many reports have pointed that CTHRC1 could exert different effects through several signaling pathways such as TGF-β, Wnt, integrin β/FAK, Src/FAK, MEK/ERK, PI3K/AKT/ERK, HIF-1α, and PKC-δ/ERK signaling pathways. As a participant in tissue remodeling or immune response, CTHRC1 may promote early-stage cancer. Several recent studies have identified CTHRC1 as an effectual prognostic biomarker for predicting tumor recurrence or metastasis. It is worth noting that CTHRC1 has different cellular localization and mechanisms of action in different cells and different microenvironments. In this article, we focus on the advances in the signaling pathways mediated by CTHRC1 in tumors.

Recently, diagnoses of radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) have become more common; prognosis is poor. It has been suggested that cancer stem cells account for radiotherapy resistance. By flow cytometry, different expression percents of CD133 and OCT4 in thyroid cancer cell lines were detected. By real-time quantitative PCR, different mRNA expression of CD133, OCT4, GLUT1, thyroglobulin (TG), thyroperoxidase (TPO) and sodium iodine symporter (NIS) was analyzed; the localization of CD133, OCT4, and NIS expression was examined using immunofluorescence confocal microscopy. Different expression of CD133, OCT4, and NIS in 21 human thyroid cancer and nodule tissues was investigated using immunohistochemistry. CD133-positive cells were isolated by magnetic sorting. Stronger colony formation ability of CD133-positive and weaker ability of CD133-negative cells in vivo were examined by colony formation. The effects of all-trans retinoic acid (ATRA) on CD133-positive cells in vivo were explored with Cell Counting Kit-8, colony formation, apoptosis, cell cycle, and ethynyl deoxyuridine assays. The ARO cell line and RAI-R DTC tissue specimens had more CD133-positive cells. NIS expression was significantly lower in RAI-R DTC tissue compared to radioiodine-sensitive DTC (RAI-DTC) tissue and specimens from patients with thyroid nodule. ATRA inhibited the stem cell characteristics of CD133-positive cells and induced CD133-positive cell differentiation to CD133-negative cells, and promoted CD133-positive cell apoptosis.

Objective: The thickened coracohumeral ligament (CHL) is an important part of the typical manifestations and magnetic resonance imaging of frozen shoulder. However, only a few clinical studies with limited cases on arthroscopic extra‐articular entire CHL release exist in the literature. This study was to evaluate the effect of arthroscopic extra‐articular entire CHL release for patients with recalcitrant frozen shoulder. Methods: From February 2014 to February 2020, 81 cases of recalcitrant frozen shoulder patients treated with surgery in a single‐center shoulder department and followed for more than 2 years were analyzed. Arthroscopic 360° capsular release was performed with intra‐articular partial release (IPR group) or additional extra‐articular entire release (IPR + EER group) of CHL. The same rehabilitation program was performed after surgery in both groups. Visual analogue scale (VAS) for pain, range of motion (ROM), and the Constant–Murley scoring system was evaluated before operation, at 3 months after operation, 6 months after operation, and the final follow‐up. T‐test, Mann–Whitney U‐test and chi‐squared test were used to compared data. Results: There were 39 patients in the IPR group, with an average follow‐up of 29.2 months. A total of Forty‐two patients in the IPR + EER group completed a mean follow‐up of 25.7 months. All incisions healed in stages. There were significant differences in Constant–Murley shoulder score, VAS score, and ROM before operation and at the final follow‐up in both groups (both P < 0.001). The VAS score of the IPR + EER group was lower than that of the IPR group at 3 months after surgery (P < 0.05), and 6 months after operation (P < 0.05). External rotation, internal rotation, and abduction of ROMs and Constant–Murley shoulder score were significantly greater in the IPR + EER group at 3 months (P < 0.001, P < 0.05, P < 0.001, P < 0.05, respectively) and 6 months after operation (P < 0.001, P < 0.05, P < 0.001, P < 0.05, respectively). At the last follow‐up, there was no significant difference in forward flexion, internal rotation, and abduction of ROMs, VAS, and the Constant–Murley shoulder score between the IPR and IPR + EER groups. The external rotation of the IPR + EER group was still greater than that of the IPR group at the last follow‐up (P < 0.001). Conclusion: Arthroscopic extra‐articular entire coracohumeral ligament release could solve early pain of shoulder joint, recover shoulder joint functions effectively, and achieve a satisfactory efficacy in the treatment of recalcitrant frozen shoulder. [ABSTRACT FROM AUTHOR]