The mechanism of miR-665 targeting GNB3 in aluminum-induced neuronal apoptosis.

BACKGROUND: Aluminum exerts neurotoxic effects through various mechanisms, mainly manifested as impaired learning and memory function. METHODS: Forty SD rats were divided into 0, 10, 20, and 40 mM maltol aluminum [Al(mal)3] groups. Cell experiments are divided into 0, 100, 200, and 400 µM Al(mal)3 dose group and control, Al(mal)3, Al(mal)3+inhibitor NC, Al(mal)3+miR-665 inhibitor intervention group. Water maze was used to detect the learning and memory function of rats, HE staining was used to observe the morphology and number of neurons in the CA1 area of the rat hippocampus, Flow cytometry was used to detect the apoptosis of PC12 cells, PCR and Western blotting were used to detect the expression of Caspase3, miR-665 and GNB3/PI3K/AKT proteins. The target binding relationship between miR-665 and GNB3 was verified by double luciferase reporter gene experiment. RESULTS: In vivo experimental results showed that with the increase of Al(mal)3 concentration, the escape latency of rats was prolonged, the target quadrant dwell time was shortened, and the number of crossing platform was reduced. Moreover, the arrangement of neurons was loose and the number decreased; the expression of Caspase3 and miR-665 increased, while the expression of GNB3/PI3K/AKT proteins decreased. In vitro experiments, with the increase of Al(mal)3 concentration, apoptosis rate of PC12 cells increased, the expression of Caspase3, miR-665 and GNB3/PI3K/AKT proteins were consistent with rat results. After inhibiting miR-665 in the intervention group experiment, apoptosis rate of PC12 cells in the aluminum exposure group decreased, the expression of Caspase3 and miR-665 decreased, and the expression of GNB3/PI3K/AKT proteins increased. CONCLUSION: MiR-665 plays an important role in aluminum induced neuronal apoptosis by targeting GNB3 and regulating the PI3K/AKT pathway.

Use of All-Male cyp17a1-Deficient Zebrafish (Danio rerio) for Evaluation of Environmental Estrogens.

Natural and synthetic environmental estrogens (EEs) are widespread and have received extensive attention. Our previous studies demonstrated that depletion of the cytochrome P450 17a1 gene (cyp17a1) leads to all-testis differentiation phenotype in zebrafish and common carp. In the present study, cyp17a1-deficient zebrafish with defective estrogen biosynthesis were used for the evaluation of EEs, as assessed by monitoring vitellogenin (vtg) expression. A rapid and sensitive assessment procedure was established with the 3-day administration of estradiol (E2), followed by examination of the transcriptional expression of vtgs in our cyp17a1-deficient fish. Compared with the control fish, a higher E2-mediated vtg upregulation observed in cyp17a1-deficient zebrafish exposed to 0.1 µg/L E2 is known to be estrogen receptor-dependent and likely due to impaired in vivo estrogen biosynthesis. The more responsive vtg expression in cyp17a1-deficient zebrafish was observed when exposed to 200 and 2000 µg/L bisphenol A (BPA) and perfluoro-1-octanesulfonate (PFOS). The estrogenic potentials of E2, BPA, and PFOS were compared and assessed by the feminization effect on ovarian differentiation in cyp17a1-deficient zebrafish from 18 to 50 days postfertilization, based on which a higher sensitivity of E2 in ovarian differentiation than BPA and PFOS was concluded. Collectively, through the higher sensitivity to EEs and the capacity to distinguish chemicals with different estrogenic potentials exhibited by the all-male cyp17a1-deficient zebrafish with impaired estrogen biosynthesis, we demonstrated that they can be used as an excellent in vivo model for the evaluation of EEs. Environ Toxicol Chem 2024;43:1062-1074. © 2024 SETAC.

A Multi-Layer Stacked Microfluidic Tactile Display With High Spatial Resolution.

Pneumatic tactile displays dynamically customize surface morphological features with reconfigurable arrays of independently addressable actuators. However, their ability to render detailed tactile patterns or fine textures is limited by the low spatial resolution. For pneumatic tactile displays, the high-density integration of pneumatic actuators within a small space (fingertip) poses a significant challenge in terms of pneumatic circuit wiring. In contrast to the structure with a single-layer layout of pipes, we propose a multi-layered stacked microfluidic pipe structure that allows for a higher density of actuators and retains their independent actuation capabilities. Based on the proposed structure, we developed a soft microfluidic tactile display with a spatial resolution of 1.25 mm. The device consists of a 5 × 5 array of independently addressable microactuators, driven by pneumatic pressure, each of which enables independent actuation of the surface film and continuous control of the height. At a relative pressure of 1000 mbar, the actuator produced a perceptible out-of-plane deformation of 0.145 mm and a force of 17.7 mN. User studies showed that subjects can easily distinguish eight tactile patterns with 96% accuracy.

Printhead on a chip: empowering droplet-based bioprinting with microfluidics.

Droplet-based bioprinting has long struggled with the manipulation and dispensation of individual cells from a printhead, hindering the fabrication of artificial cellular structures with high precision. The integration of modern microfluidic modules into the printhead of a bioprinter is emerging as one approach to overcome this bottleneck. This convergence allows for high-accuracy manipulation and spatial control over placement of cells during printing, and enables the fabrication of cell arrays and hierarchical heterogenous microtissues, opening new applications in bioanalysis and high-throughput screening. In this review, we summarize recent developments in the use of microfluidics in droplet printing systems, with consideration of the working principles; present applications extended through microfluidic features; and discuss the future of this technology.

Optimal allocation for land in an arid inland basin in northwest China: framework and application based on CLUE-S and MCR models.

Reasonable planning of the limited land resources can promote the coordinated development of social economic and ecological protection. It is very important to optimize the rational distribution of land resources in the arid inland river basin because of the scarce land. In this paper, the GIS technologies of spatial analysis, conversion of land use, and its effects at small regional extent (CLUE-S) and minimum cumulative resistance (MCR) model were used to optimize the land allocation. The ecological security pattern (ESP) was constructed through using MCR model, which included ecological source and resistance surface. The dynamics of land use and spatial optimizing allocation of Shiyang River Basin in 2025 and 2030 was simulated under three different optimization scenarios including farmland protection scenario (FPS), free development scenario (FDS), and ecological security pattern scenario (ESPS). It was found that under ESPS, farmland was reduced, but woodland, grassland, and water body were increased significantly. Under FPS, land for construction was controlled effectively, a large part of homestead was converted into farmland, and the potential of unused land was developed vigorously. Furthermore, the current FDS and macro policy guidance should be comprehensively considered. The ESPS was more suitable for the scientific development of Shiyang River Basin on a long view. The combination of CLUE-S and MCR can effectively improve the optimization methods under ecological process and ecological resistance of landscape elements.

Protopanaxadiol manipulates gut microbiota to promote bone marrow hematopoiesis and enhance immunity in cyclophosphamide-induced immunosuppression mice.

Protopanaxadiol (PPD) has potential immunomodulatory effects, but the underlying mechanism remains unclear. Here, we explored the potential roles of gut microbiota in the immunity regulation mechanisms of PPD using a cyclophosphamide (CTX)-induced immunosuppression mouse model. Our results showed that a medium dose of PPD (PPD-M, 50 mg/kg) effectively ameliorated the immunosuppression induced by CTX treatment by promoting bone marrow hematopoiesis, increasing the number of splenic T lymphocytes and regulating the secretion of serum immunoglobulins and cytokines. Meanwhile, PPD-M protected against CTX-induced gut microbiota dysbiosis by increasing the relative abundance of Lactobacillus, Oscillospirales, Turicibacter, Coldextribacter, Lachnospiraceae, Dubosiella, and Alloprevotella and reducing the relative abundance of Escherichia-Shigella. Importantly, PPD-M lost the ability to promote bone marrow hematopoiesis and enhance immunity when the gut microbiota was depleted by broad-spectrum antibiotics. Moreover, PPD-M promoted the production of microbiota-derived immune-enhancing metabolites including cucurbitacin C, l-gulonolactone, ceramide, DG, prostaglandin E2 ethanolamide, palmitoyl glucuronide, 9R,10S-epoxy-stearic acid, and 9'-carboxy-gamma-chromanol. KEGG topology analysis showed that the PPD-M treatment significantly enriched the sphingolipid metabolic pathway with ceramide as a main metabolite. Our findings reveal that PPD enhances immunity by manipulating gut microbiota and has the potential to be used as an immunomodulator in cancer chemotherapy.

A review of the botany, ethnopharmacology, phytochemistry, pharmacology, toxicology and quality of Anemarrhena asphodeloides Bunge.

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizomes of Anemarrhena asphodeloides Bunge., belonging to the family Liliaceae, are named 'Zhi-mu' according to traditional Chinese medicine theory. It is a medicinal plant that has long been used as a tonic agent in various ethnomedicinal systems in East Asia, especially in China, and also for treating arthralgia, hematochezia, tidal fever, night sweats, cough, dry mouth and tongue, hemoptysis, etc. THE ARM OF THE REVIEW: The review aims to provide a systematic overview of botany, ethnopharmacology, phytochemistry, pharmacology, toxicology and quality control of Anemarrhena asphodeloides and to explore the future therapeutic potential and scientific potential of this plant. MATERIALS AND METHODS: A comprehensive literature search was performed on Anemarrhena asphodeloides using scientific databases including Web of Science, PubMed, Google Scholar, CNKI, Elsevier, SpringerLink, ACS publications, ancient books, Doctoral and master's Theses. Collected data from different sources was comprehensively summarised for botany, ethnopharmacology, phytochemistry, pharmacology, toxicology and quality control of Anemarrhena asphodeloides. RESULTS: A comprehensive analysis of the literature as mentioned above confirmed that the ethnomedical uses of Anemarrhena asphodeloides had a history of thousands of years in eastern Asian countries. Two hundred sixty-nine compounds have been identified from Anemarrhena asphodeloides, including steroidal saponins, flavonoids, phenylpropanoids, alkaloids, steroids, organic acids, polysaccharides, benzophenones and other ingredients. Studies have shown that the extracts and compounds from Anemarrhena asphodeloides have extensive pharmacological activities, such as nervous system activity, antitumour, anti-inflammatory, antidiabetic, antiosteoporotic, antiallergic, antiplatelet aggregation, antimicrobial, antiviral, anti-ageing, hair growth promoting, preventing cell damage, etc. Evaluating the quality and toxicity of Anemarrhena asphodeloides is essential to confirm its safe use in humans. CONCLUSION: Anemarrhena asphodeloides is widely used in traditional medicine and have diverse chemical constituents with obvious biological activities. Nevertheless, more studies should be carried out in animals and humans to evaluate the cellular and molecular mechanisms involved in its biological activity and confirm its safe use.

PCL-nHAC/Mg-Ca alloy composite and preliminary study of its osteogenesis property.

Owing to their excellent properties, magnesium alloys are widely used in bone tissue engineering. However, considerable work has been conducted to control the degradation rate and improve the cytocompatibility of magnesium alloys. In this study, low-cost production introduced a new bone repair composite (PCL-nHAC/Mg-Ca), which was composed of nano-hydroxylapatite-collagen (nHAC), polycaprolactone (PCL) and Mg-Ca alloy substrate treated by micro- arc oxidation (MAO). The experimental results showed that compared with the Mg-Ca alloy treated by MAO alone, the PCL-nHAC/Mg-Ca composite has a porous structure and a slower degradation rate. Cell experiments showed that the PCL-nHAC/Mg-Ca composite had good biocompatibility and significantly enhanced the proliferation of the MC3T3-E1 cells. The rabbit skull defect model further proved that the PCL-nHAC/Mg-Ca composite could regulate the degradation rate of the Mg-Ca alloy and promote the formation of bone tissue. Histological analyses showed that the PCL-nHAC/Mg-Ca composite had good stability in vivo and could better accelerate bone formation.

The Evolution of Pancreatic Islet Function in a Diabetic Patient after Pancreatic Neuroendocrine Neoplasm Surgery: A Case Report.

BACKGROUND: Pancreatic neuroendocrine neoplasms (pNENs) are rare primary tumors of the pancreas. Although these tumors are heterogeneous and can be classified as functional or non-functional according to pancreatic endocrine biomarkers, the more prevalent type is non-functional pNENs with endocrine differentiation but with non-specific symptoms and often late diagnoses. The treatment option for patients often involves surgical management, but the reported outcomes, especially on insulin secretion change and the trend of diabetes in these patients, varied to date. Hence, the purpose of this clinical report is to study the functional change of pancreatic ß- cell corresponding to the mass of tumorectomy of pNEN in a diabetic patient. CASE PRESENTATION: We reported that a 39-year-old man with diabetes was found complicated with neuroendocrine neoplasm. He was admitted to the General Surgery of our hospital for further examination and therapy. The patient received a pancreatectomy + splenectomy + lymphadenectomy on the pancreatic body and tail. We analyzed the pancreatic mass change and performed Oral Glucose Tolerance Test (OGTT) before and after the surgery to evaluate the function of the pancreas. CONCLUSION: This case may provide us a reference to predict the extent of islet function loss before the pancreatectomy, and apply personalized hypoglycemic therapy after surgery in these patients.

Indirect transmission and disinfection strategies on heterogeneous networks.

Besides direct contacts of individuals, indirect contacts with environments being the medium is another route of epidemic transmission, which most previous studies have ignored. Disinfection is one of the most effective and commonly used measures to prevent and control epidemic spreading. In this paper, we propose a metapopulationlike model incorporating direct and indirect transmissions for susceptible-infected-susceptible-like epidemics on heterogeneous networks. Furthermore, we explore the epidemic spreading process with heterogeneous disinfection on both spatial and time dimensions. Specifically, we put forward three types of disinfection strategies, namely, the static disinfection strategy, the random time disinfection strategy, and the event-triggered disinfection strategy. Comparative analysis of the three strategies suggests that managers should prioritize disinfection resource allocation to large-flow environments, especially when disinfection resources are limited. In addition, timely disinfection of environments with infected visitors is an effective and economical strategy. Our model sheds light on the interplay dynamics of indirect transmission and disinfection and the results provide theoretical support for governors to select proper disinfection strategies in practical scenarios.

Research progress on Walnut oil: Bioactive compounds, health benefits, extraction methods, and medicinal uses.

Walnut oil is extracted from walnut kernels (Juglans regia Linne) or iron walnut kernels (Juhlans sigillata Dode). The percentage of oil in walnuts is 52%-70%. The main constituents in oil are fatty acids, phenols, sterols, squalene, melatonin, vitamins, and minerals. Many extraction methods such as supercritical carbon dioxide extraction, maceration, modified "bligh and dyer extraction," aqueous enzymatic extraction, ultrasonic extraction, soxhlet extraction, and cold-press extraction methods are reported in the literature. Walnut oil showed anti-inflammatory, antitumor, antioxidant, immunomodulatory, neuroprotective, cardioprotective, antidiabetic, and antihyperlipidemic activities. The reported data in the literature suggest that walnut oil has many health benefits. This review summarizes the extraction methods, bioactive constituents, health benefits, and pharmacological actions of walnut oil. PRACTICAL APPLICATIONS: Walnut oil is a natural vegetable oil of significant importance due to their nutritional, and intelligence-boosting benefits. Several factors, including the processing parameters and the phytochemical profile, affect walnut oil products' flavor and color. In addition, storage environment of walnut oil can also affect walnut oil quality. Apart from the predominant ingredient fatty acids, the chemical composition of walnut oil comprises phenols, sterols, squalene, melatonin, vitamins, and minerals. These bioactive compounds are of potential value owing to their health-promoting benefits, including antioxidant, antitumor, and cholesterol-lowering effects. Many chemical constituents were isolated from walnut oil; however, all the compounds are not explored for their possible medicinal value. Thus, clinical studies, exploration of the therapeutic potential and the molecular mechanisms of all the compounds, and development of convenient dosage forms either for therapeutic or functional food purposes are warranted.

The chemistry and efficacy benefits of polysaccharides from Atractylodes macrocephala Koidz.

Atractylodes macrocephala Koidz (AM), traditional Chinese medicine (TCM) with many medicinal values, has a long usage history in China and other oriental countries. The phytochemical investigation revealed the presence of volatile oils, polysaccharides, lactones, flavonoids, and others. The polysaccharides from AM are important medicinal components, mainly composed of glucose (Glc), galactose (Gal), rhamnose (Rha), arabinose (Ara), mannose (Man), galacturonic acid (GalA) and xylose (Xyl). It also showed valuable bioactivities, such as immunomodulatory, antitumour, gastroprotective and intestinal health-promoting, hepatoprotective, hypoglycaemic as well as other activities. At the same time, based on its special structure and pharmacological activity, it can also be used as immune adjuvant, natural plant supplement and vaccine adjuvant. The aim of this review is to summarize and critically analyze up-to-data on the chemical compositions, biological activities and applications of polysaccharide from AM based on scientific literatures in recent years.

Assessment of Spatio-Temporal Changes for Ecosystem Health: A Case Study of Hexi Corridor, Northwest China.

Ecosystem health (EH) is important for ensuring sustainable development, and the main goal of environmental protection and governance, especially for ecological fragile areas. Scientific assessment of EH can improve decision-making ability and inform sustainable development. In this paper, the effects of natural and social environment were integrated to reflect the characteristics of EH based on a comprehensive assessment system including ecosystem vigor (EV), ecosystem organization (EO), ecosystem resilience (ER), and the ratio of supply to demand of ecosystem services (ESDR) from the perspectives of ecological integrity and human demand for ecosystem services (ES). The Entire-Array-Polygon (EAP) method was applied to calculate an ecosystem health index (EHI) and analyze spatio-temporal change from 2000 to 2020 in Hexi Corridor (HC), Northwest China. The results showed that: (1) The spatial distribution of EV, EO, ER, and ESDR was generally consistent, with a low spatial distribution in the northwest and high in the southeast, the values showed an overall increasing trend from 2000 to 2020. (2) The spatial distribution of EHI was high in the northwest and central regions, and low in the southwest, reflected a moderate health level. The proportion of area with well and relatively well health was increasing, which indicated that EH showed an improving trend. (3) The significantly decrease areas of EHI were mainly located in urban areas, and the increases areas were mainly located outside of urban areas. The distribution of the EH condition has obvious orientation characteristics. The results of the study provide theoretical and practical implications for regional ecological conservation and management.

Solasonine Inhibits Pancreatic Cancer Progression With Involvement of Ferroptosis Induction.

Pancreatic cancer is a highly fatal malignant tumor of the digestive system. It is characterized by early metastasis and high mortality rates. Solasonine, a steroidal alkaloid, is derived from Solanum nigrum L., a natural herb. Solasonine is associated with excellent anti-tumor effects, however, its effects on pancreatic cancer have not been fully established. Pancreatic cancer cells (PANC-1 and CFPAC-1) were used to verify the in vitro and in vivo effects of solasonine. Metabolomics were used to evaluate its underlying mechanisms. Solasonine promoted PANC-1 and CFPAC-1 cell apoptosis while inhibiting their proliferation, migration and invasion. Mouse xenograft models and metastasis models of ANC-1 and CFPAC-1 confirmed that solasonine blocked tumor formation and metastasis. Metabolomics confirmed the effects of solasonine on glutathione metabolism and SLC7A11-mediated ferroptosis. Furthermore, Co-Immunoprecipitation and Duolink® in situ PLA confirmed that OTUB1, a deubiquitylating enzyme, interacted with SLC7A11 and solasonine to enhance ubiquitinated degradation of SLC7A11 in PANC-1 and CFPAC-1 cells. Besides, molecular docking confirmed that solasonine directly bound TFAP2A and suppressed its protein levels. Bioinformatics and luciferase assays revealed that TFAP2A binds the OTUB1 promoter region, thereby promoting its transcription. In summary, solasonine inhibits the TFAP2A/OTUB1 SLC7A11 axis to activate ferroptosis and suppress pancreatic cancer cell progression.

Effect of Pheretima aspergillum on reducing fibrosis: A systematic review and meta-analysis.

Background: Pheretima aspergillum (common name: Earthworm, Chinese name: dilong) has been used in traditional Chinese medicine for thousands of years. Recently, a few scientific studies have investigated the antifibrotic effects of Dilong extract (DE) and produced controversial results. We conducted a meta-analysis to make an informed decision on the antifibrotic effects of Dilong extract. Methods: The studies on antifibrotic effects of Dilong extract published until July 2022 in the scientific databases [PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), VIP database for Chinese Technical Periodicals, SinoMed and WanFang database] were reviewed. The RevMan 5.4.1 software was used for standardized mean difference (SMD) analysis. Two researchers independently reviewed all the studies, and their quality was assessed using the Cochrane risk of bias tool. Results: A total of 325 studies were found in the scientific databases; however, only 13 studies met the criteria for analysis. Dilong extract treatment was associated with antifibrotic effects via inhibiting the transforming growth factor beta 1 (TGF-ß1, SMD = -3.16, 95% CI: -4.18, -2.14, p < .00001) and alpha-smooth muscle actin (α-SMA: SMD = -2.57, 95% CI: -3.47, -1.66, p < .00001). Conclusion: Dilong extract effectively reduces tissue fibrosis; thus, further scientific studies should be conducted to investigate and develop it for clinical use. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022357141.

Dahuang Danshen Decoction Inhibits Pancreatic Fibrosis by Regulating Oxidative Stress and Endoplasmic Reticulum Stress.

BACKGROUND: In Traditional Chinese Medicine (TCM), Dahuang Danshen decoction (DD) is used to treat pancreatic fibrosis. Pancreatic fibrosis is a typical manifestation of chronic pancreatitis (CP), which affects the digestive system. The therapeutic mechanisms of DD in pancreatic fibrosis are unclear. AIM: This study aimed to investigate the regulatory mechanisms of DD on oxidative stress and endoplasmic reticulum stress in CP. MATERIALS AND METHODS: Experimental rats were intraperitoneally injected with 500 mg/kg BW of diethyldithiocarbamate (DDC) twice a week for six weeks to induce CP. At the same time, DD was administered orally at daily doses of 1.37 g/kg BW, 2.74 g/kg BW, and 5.48 g/kg BW to evaluate its treatment effects on CP. After all treatments, pancreatic tissues were harvested and subjected to H&E staining. Transmission electron microscopy (TEM) was also performed to show the endoplasmic reticulum structure in the pancreatic tissues. Immunohistochemistry was used to detect the α-SMA expression level in the pancreatic tissues. Metabolomics analysis of the serum and proteomics analysis of the pancreatic tissues were performed to reveal the changes of endogenous metabolites and proteins, respectively. Concentrations of GSH, MDA, SOD, ROS, col-1, and col-3 were determined using corresponding kits. The western blotting method was used to determine the protein levels of Keap-1, HO-1, NQO1, Nrf2, GRP, JNK, and caspase 12. The pancreatic mRNA levels of NQO1, GPX1, HO-1, GST-π, GRP, JNK, and caspase 12 were also determined by quantitative PCR. The interactions between TCM components and Keap-1 were investigated by molecular docking modeling. RESULTS: The pathohistological results demonstrated that DD could ameliorate DDC-induced CP in vivo, indicated by reduction of α-SMA, col-1, col-3, TNF-α, and IL-6. DD increased serum levels of GSH and SOD but reduced pancreatic ROS. DD decreased cytoplasmic Keap-1 and increased Nrf2 nuclear localization. Correspondingly, DD increased the expression levels of Nrf2 downstream antioxidant genes NQO1, GPX1, HO-1, and GST-π. DD also decreased ERS hallmarks caspase 12 cleavage and GRP expression. Eventually, DD inhibited PSC activation by reducing JNK phosphorylation and MMK-3/p38 expression. Molecular docking analysis showed that salvianolic acid B and emodin had a good binding affinity toward Keap-1. CONCLUSIONS: These results demonstrated that DD could ameliorate the oxidative and endoplasmic reticulum stress through releasing Nrf2 from Keap-1 binding and inducing the downstream antioxidant enzymes. As a result, DD could thwart pancreatic fibrosis by inhibiting PSCs activation, which was induced by OS and ERS through JNK and MMK3/p38 pathways.

Using Liposomes to Alleviate the Toxicity of Chelerythrine, a Natural PKC Inhibitor, in Treating Non-Small Cell Lung Cancer.

AIM OF THE STUDY: CHE can inhibit the proliferation of lung cancer cells and induce apoptosis. However, despite having in vivo toxicity, CHE has not been thoroughly investigated in term of its in vivo antitumor effect. The present study evaluated the antitumor effect of CHE on non-small cell lung cancer cell line HCC827. METHODS: The antitumor effect of CHE on HCC827 was evaluated, and its potential work mechanism was investigated. CHE long circulation liposomes (CHELPs) modified with polyethylene glycol have been optimized and characterized by in vivo pharmacokinetic studies. A HCC827 xenograft model was developed on BALB/c nude mice for the assessment of the effects of CHE and CHELP. RESULTS: CHE might inhibit HCC827 growth through the ROS/PKC-ϵ/caspase 3 pathway and glycolysis. The optimized CHELP remained stable after storage for 10 days at 4°C and exhibited sustained drug release, showing approximately one-fifteenth of the in vivo clearance rate and 86 times the absorption concentration of free drug. While increasing the bioavailability of CHE, CHELP showed a good therapeutic effect on HCC827 tumor-bearing nude mice and reduced the toxicity of the free drug, improving the safety of CHE. CONCLUSIONS: CHE is a candidate drug for NSCLC, and liposomes are effective in alleviating the toxicity of CHE.

Low TSH Levels Within Euthyroid Range Could Play a Negative Role on Bone Mineral Density in Postmenopausal Women with Type 2 Diabetes.

OBJECTIVE: We aimed to evaluate the relationship between thyroid-stimulating hormone (TSH) and bone mineral density (BMD) in euthyroid type 2 diabetes (T2D). METHODS: This retrospective analysis enrolled 439 T2D patients with normal thyroid function, including 226 males and 213 females. All the female patients were postmenopausal. Serum glycosylated hemoglobin A1c (HbA1c), TSH, free triiodothyronine (FT3), and free thyroxine (FT4) concentrations were analyzed. BMD of the lumbar spine (L1-L4), femoral neck, and hip joint was determined using dual-energy X-ray absorptiometry. RESULTS: The patients were grouped based on tri-sectional quantiles of the TSH levels: 0.55~1.70mIU/L (Group 1), 1.71~2.58mIU/L (Group 2), and 2.59~4.74mIU/L (Group 3). Our data showed that, in male patients, no difference in BMD was identified among groups. In postmenopausal women, unlike at the lumbar spine (P = 0.459), the mean BMD at the femoral neck (P = 0.014) and hip joint (P = 0.014) had a statistical difference among groups and increased with TSH level. In addition, our analysis demonstrated that TSH levels shown no correlation with BMD at all sites in males. However, in females, BMD at the femoral neck (r = 0.156, P = 0.023) and hip joint (r = 0.172, P = 0.012) had a positive correlation with TSH levels. After adjusting for age and BMI, multiple regression analysis showed that TSH levels influenced BMD at the femoral neck (ß = 0.188, P = 0.001) and hip joint (ß = 0.204, P = 0.001) in female patients. CONCLUSION: In summary, our data demonstrates that low TSH levels are associated with decreased BMD at the femoral neck and hip joint in postmenopausal T2D women with euthyroidism.

Psoriasis Exacerbates the State of Insulin Resistance in Patients with Type 2 Diabetes.

PURPOSE: Although psoriasis (PsO) is highly associated with insulin resistance (IR), the role of PsO on activity of insulin secretion or its action in diabetic patients has not been explored. MATERIALS AND METHODS: In-patient data on type 2 diabetes (T2D) with or without PsO from 2016-2019 in our hospital were analyzed. Data for 42 diabetic patients with PsO were compared with that of the control group (T2D only). Blood examinations with reference to the levels of fasting blood glucose, C-peptide, insulin, HbA1c, plasma lipids, lipoproteins, and kidney function were explored. HOMA-IR and HOMA-ß models were established to explore IR and pancreatic ß-cell function. RESULTS: HOMA-IR level was significantly higher (P=0.0003<0.05) in patients with PsO compared with the controls. Although the durations of diabetes in patients with PsO were significantly shorter compared with that of patients with diabetes only (P=0.012<0.05), analysis of mean BMI, eGFR, plasma lipids, and lipoprotein showed no significant differences. Analysis of the level of fasting glucose and HOMA-ß showed no statistical differences between the two groups. On the other hand, the levels of C-peptide of PsO group were significantly high in both fasting state (P=0.0182<0.05) and after glucose challenge (P=0.0011<0.01). CONCLUSION: The findings of this study show that under the same fasting conditions, patients with PsO may have relatively preserved pancreatic ß-cell function, and PsO significantly increases IR.

Efficacy and safety of Shi-style cervical manipulation therapy for treating acute and subacute neck pain: study protocol for a randomized controlled trial.

BACKGROUND: Neck pain is a common clinical disease, which seriously affects people's mental health and quality of life and results in loss of social productivity. Improving neck pain's curative effect and reducing its recurrence rate are major medical problems. Shi's manipulation therapy has unique advantages and technical features that aid in the diagnosis and treatment of neck pain. Compared with first-line non-steroidal anti-inflammatory drug (NSAID) treatment of neck pain, Shi's cervical manipulation lacks the relevant research basis of therapeutic advantage, safety, and satisfaction for treating acute and subacute neck pain. Herein, we aim to confirm our hypothesis in a clinical trial that the safety and efficacy of Shi's cervical manipulation will be more effective, safer, and more satisfactory than NSAIDs to treat acute and subacute neck pain. METHODS: In this multicenter, positive-controlled, randomized clinical trial, traditional analgesic drug (NSAID) is used to evaluate and show that Shi's manipulation is more effective, safe, and satisfactory for treating acute and subacute neck pain. Overall, 240 subjects are randomly divided into the trial and control groups, with both groups treated by the corresponding main intervention method for up to 12 weeks. Clinical data will be collected before the intervention and immediately after the first treatment; at 3 days and 1, 2, 4, 8, and 12 weeks after the intervention; and at 26 and 52 weeks after treatment follow-up of clinical observation index data collection. The clinical observation indices are as follows: (1) cervical pain is the primary observation index, measured by Numerical Rating Scale. The secondary indices include the following: (2) cervical dysfunction index, measured by patient self-evaluation using cervical Neck Disability Index; (3) cervical activity measurement, measured by the cervical vertebra mobility measurement program of Android mobile phone system; (4) overall improvement, measured by patient self-evaluation with SF-36; and (5) satisfactory treatment, determined by patient self-evaluation. DISCUSSION: We will discuss whether Shi's cervical manipulation has greater advantages in efficacy, safety, and satisfaction of acute and subacute neck pain than traditional NSAIDs, to provide a scientific basis for the dissemination and application of Shi's cervical manipulation. TRIAL REGISTRATION: China Registered Clinical Trial Registration Center ChiCTR1900021371 . Registered on 17 February 2019.