Objective To investigate the effect of vitamin B6(VB6)on vascular endothelial injury of atherosclerosis(AS)mice and its mechanism.Methods Thirty-six ApoE-/-mice were randomly divided into control group,AS group,VB6 group,AS+LiCl group,AS+VB6 group and AS+VB6+LiCl group,with 6 mice in each group.The mice in the AS group,AS+LiCl group,AS+VB6 group and AS+VB6+LiCl group were fed with high-fat diet for 12 weeks to establish the AS model;the mice in the control group and VB6 group were given regular diet and normal drinking water for 12 weeks.After 12 weeks,the mice in the control group were given conventional diet and the same volume of physiological saline as the VB6 group daily by gavage;the mice in the VB6 group were given routine diet and VB6(50 mg·kg-1)by gavage daily;the mice in the AS+LiCl group were given high-fat diet continuously and LiCl(1 mg·kg-1)by gavage daily;the mice in the AS+VB6 group were given high-fat diet continuously and VB6(50 mg·kg-1)by gavage daily;the mice in the AS+VB6+LiCl group were given high-fat diet continuously and VB6(50 mg·kg-1),LiCl(1 mg·kg-1)by gavage daily;all mice were intervened for 4 weeks.After intervention,the serum nitric oxide(NO),malondialdehyde(MD A)levels and superoxide dismutase(SOD)activity of mice in each group were measured by enzyme linked immunosorbent assay.Hematoxylin-eosin staining was used to observe the morphology of thoracic aortic tissue of mice in each group and the percentage of AS plaque area to total vascular area was calculated.The vasodilatation rate of thoracic aorta was detected by isolated vascular ring experiment.The expression of sodium/hydrogen exchanger 1(NHE1)protein in thoracic aorta was detected by immunohistochemistry.Results Compared with the control group,the NO level and SOD activity in the serum of mice in the AS group decreased,while the MDA level increased(P＜0.05);there was no significant difference in the NO,MDA levels and SOD activity in the serum of mice between the VB6 group and the control group(P＞0.05).Compared with the AS group,the serum NO level and SOD activity of mice in the AS+VB6 group increased,while the MDA level decreased(P＜0.05);there was no significant difference in serum NO,MDA levels and SOD activity of mice between the AS+LiCl group,AS+VB6+LiCl group and AS group(P＞0.05).Compared with the AS+VB6 group,the serum NO level and SOD activity of mice in the AS+VB6+LiCl group decreased,while the MDA level increased(P＜0.05).The percentage of AS plaque area to total vascular area of mice in the AS group was significantly higher than that in the control group(P＜0.05);there was no significant difference in the percentage of AS plaque area to total vascular area of mice among the VB6 group and the control group(P＜0.05).The percentage of AS plaque area to total vascular area of mice in the AS+VB6 group was significantly lower than that in the AS group(P＜0.05);there was no significant difference in the percentage of AS plaque area to total vascular area of mice between the AS+LiCl group,AS+VB6+LiCl group and AS group(P＜0.05).The percentage of AS plaque area to total vascular area of mice in the AS+VB6+LiCl group was significantly higher than that in the AS+VB6 group(P＜0.05).In the control group,the vascular endothelium of mice was smooth with orderly arrangement of cells;in the AS group,AS+LiCl group and AS+VB6+LiCl group,the tissue structure of vascular of mice was disordered and the vascular endothelium was rough;in the VB6 group and AS+VB6 group,the vascular wall structure of mice was normal,the vascular endothelium was smooth,and the cells were arranged orderly.The vasodilatation rate of thoracic aorta of mice induced by acetylcholine(Ach)in the AS group was significantly lower than that in the control group(P＜0.05);there was no significant difference in the vasodilatation rate of thoracic aorta of mice induced by Ach between the VB6 group and the control group(P＞0.05).The vasodilatation rate of thoracic aorta of mice induced by Ach in the AS+VB6 group was significantly lower than that in the AS group(P＜0.05);there was no significant difference in the vasodilatation rate of thoracic aorta of mice induced by Ach between AS+LiCl group,AS+VB6+LiCl group and AS group(P＞0.05).The vasodilatation rate of thoracic aorta of mice induced by Ach in the AS+VB6+LiCl group was significantly higher than that in the AS+VB6 group(P＜0.05).There was no significant difference in the vasodilatation rate of thoracic aorta of mice induced by sodium nitroprusside among the six groups(P＞0.05).The percentage of NHE1 expression in the thoracic aorta of mice in the AS group was significantly higher than that in the control group(P＜0.05);there was no significant difference in the percentage of NHE1 expression in the thoracic aorta of mice between the VB6 group and the control group(P＞0.05).The percentage of NHE1 expression in the thoracic aorta of mice in the AS+VB6 group was significantly lower than that in the AS group(P＜0.05);there was no significant difference in the percentage of NHE1 expression in the thoracic aorta of mice among the AS+LiCl group,AS+VB6+LiCl group and the AS group(P＞0.05).The percentage of NHE1 expression in the thoracic aorta of mice in the AS+VB6+LiCl group was significantly higher than that in the AS+VB6 group(P＜0.05).Conclusion VB6 can improve vascular endothelial injury in AS mice via inhibiting the expression of NHE1 protein.

Objective To evaluate the efficacy,safety and economy of teriparatide in the treatment of osteoporosis.Methods PubMed,Embase,Cochrane Library,Web of Science,CNKI,WanFang Data,VIP databases and websites related to health technology evaluation were systematically searched to collect high-quality clinical evidence and economic evaluation literature of teriparatide in the treatment of osteoporosis from the inception to January 20,2023.Two researchers independently identified studies,extracted data,assessed the quality of included studies,and descriptive analyzed and summarised the results.Results A total of 25 literatures were included,involving 3 HTA reports,15 systematic review/Meta-analyses and 7 economic studies were included.In terms of effectiveness,the evaluation results showed that teriparatide could improve bone mineral density in patients with osteoporosis,reduce the incidence of vertebral/non-vertebral fractures in primary and secondary osteoporosis and prevent the fractures in postmenopausal osteoporosis compared to bisphosphonates and placebos.In terms of safety,teriparatide was proven to be safe with no elevated risk of adverse drug reactions.In terms of economic cost,teriparatide has a higher cost and economic disadvantage compared with bisphosphonates,however,for people with severe postmenopausal osteoporosis and high risk of fracture,teriparatide can be considered as a potential cost-effect treatment option.Conclusion Teriparatide is effective and safe in the treatment of osteoporosis,but it is not cost-effective advantages compared with the existing other anti-osteoporosis medications.

Objective To investigate the effects of transcutaneous electrical acupoint stimulation(TEAS)combined with multimodal analgesia on short-term and long-term joint function after total knee arthroplasty(TKA).Methods Totally 110 patients with TKA were divided into the treatment group and the control group according to random number table method,with 55 cases in each group.The control group was treated with multimodal analgesia,and the treatment group was treated with TEAS on the basis of multimodal analgesia.The VAS score,pain threshold value,WOMAC score and SF-12 score of the two groups before and at different time points after operation were recorded and analyzed.Results The VAS score of the treatment group was lower than that of the control group on the 3rd and 7th day after operation(P<0.05).On the 7th day after operation,the knee pain threshold in the treatment group was higher than that in the control group(P<0.05).The WOMAC score of the treatment group was lower than that of the control group at the 1st,2nd,4th and 12th week after operation(P<0.05).At the 4th and 12th week after operation,the SF-12 score of the treatment group was higher than that of the control group(P<0.05).Conclusion TEAS combined with multimodal analgesia can relieve the pain after TKA,and promote the recovery of joint function in the short term and long term,and the improvement effect in the short term is more obvious than that in the long term.

Objective To summarize the clinical effect and adverse reactions of avatrombopag combined with tacrolimus in the treatment of elderly patient with refractory severe aplastic anemia. Methods An elderly patient with refractory severe aplastic anemia was treated with avatrombopag and tacrolimus, and the literature review on the mechanism of action and safety of avatrombopag and tacrolimus was conducted. Results The patient was treated with a combination of cyclosporine, testosterone undecanoate, and itraconazole for 6 months without success, and developed liver and kidney dysfunction. The medication was discontinued, and the patient was treated with a combination of avatrombopag (20 mg, once per day) and tacrolimus (1 mg, twice per day). After 9 months of treatment, the patient's platelet count increased to 54×10⁹/L, the hemoglobin increased to 124 g/L, the white blood cells increased to 8.23×10⁹/L, liver and kidney function also returned to normal level, and no other adverse reactions such as thrombotic events were observed. After treatment, CD4/CD8 decreased, CD8⁺ T cells increased, and the proportion of Treg cells increased as well. Conclusion The combination of avatrombopag and tacrolimus is effective and well tolerated in the treatment of elderly patient with refractory aplastic anemia, but the long-term follow-up observation and continued accumulation of cases are still needed in the future.

Objective:To evaluate the role of cold-inducible RNA-binding protein (CIRP) in acute renal injury in a mouse model of myocardial ischemia-reperfusion (I/R) and the relationship with nuclear factor kappa B (NF-κB) signaling pathway.Methods:Twenty-four SPF-grade healthy male C57BL/6 mice, aged 6-8 weeks, with body mass index of 24-28 g, were divided into 3 groups ( n=8 each) using a random number table method: sham operation group (Sham group), myocardial I/R group (I/R group) and myocardial I/R + CIRP-derived peptide C23 group (I/R+ C23 group). The model of myocardial I/R was developed by ligation of the left anterior descending coronary artery for 30 min followed by 120-min reperfusion in anesthetized animals. CIRP-derived peptide C23 8 mg/kg was intraperitoneally injected before myocardial ischemia and reperfusion in I/R+ C23 group, while Sham group was only threaded without ligation. Blood samples were collected from the right internal carotid artery at 120 min of reperfusion for determination of the serum creatine kinase isoenzymes (CK-MB), lactic dehydrogenase (LDH), creatinine (Cr) and blood urea nitrogen (BUN) concentrations. Renal tissues were obtained for examination of the pathological changes, and the tubular injury score was assessed. The expression of NF-κB, phosphorylated NF-κB (p-NF-κB), Nod-like receptor protein 3 (NLRP3), interleukin-1beta (IL-1β) and IL-18 in renal tissues was detected by Western blot. The expression of Toll-like receptor 4 (TLR4), NLRP3, IL-1β, TNF-α and IL-6 mRNA was determined by real-time polymerase chain reaction. Results:Compared with Sham group, the levels of serum CK-MB, LDH, Cr and BUN and renal tubule injury score were significantly increased, the expression of p-NF-κB, NLRP3, IL-1β and IL-18 was up-regulated, the expression of TLR4, NLRP3, IL-1β, TNF-α and IL-6 mRNA was up-regulated ( P<0.05), and the pathological injury to renal tissues was aggravated in I/R group. Compared with I/R group, the serum CK-MB, LDH, Cr, BUN and renal tubular injury score were significantly decreased, and the expression of p-NF-κB, NLRP3, IL-1β and and IL-18 was down-regulated, the expression of TLR4, NLRP3, IL-1β, TNF-α and IL-6 mRNA was down-regulated ( P<0.05), and the pathological injury to renal tissues was alleviated in I/R+ C23 group. Conclusions:CIRP is involved in the process of acute renal injury in a mouse model of myocardial I/R, which is associated with activation of NF-κB signaling pathway and promotion of inflammatory responses.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Type 2 diabetes mellitus (T2DM) therapy is facing the challenges of long-term medication and gradual destruction of pancreatic islet β-cells. Therefore, it is timely to develop oral prolonged action formulations to improve compliance, while restoring β-cells survival and function. Herein, we designed a simple nanoparticle with enhanced oral absorption and pancreas accumulation property, which combined apical sodium-dependent bile acid transporter-mediated intestinal uptake and lymphatic transportation. In this system, taurocholic acid (TCA) modified poly(lactic-co-glycolic acid) (PLGA) was employed to achieve pancreas location, hydroxychloroquine (HCQ) was loaded to execute therapeutic efficacy, and 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC) was introduced as stabilizer together with synergist (PLGA-TCA/DLPC/HCQ). In vitro and in vivo results have proven that PLGA-TCA/DLPC/HCQ reversed the pancreatic islets damage and dysfunction, thus impeding hyperglycemia progression and restoring systemic glucose homeostasis via only once administration every day. In terms of mechanism PLGA-TCA/DLPC/HCQ ameliorated oxidative stress, remodeled the inflammatory pancreas microenvironment, and activated PI3K/AKT signaling pathway without obvious toxicity. This strategy not only provides an oral delivery platform for increasing absorption and pancreas targetability but also opens a new avenue for thorough T2DM treatment.

Purpose: Knowing the distinction between benign and borderline/malignant phyllodes tumors (PTs) can help in the surgical treatment course. Herein, we investigated the value of magnetic resonance imaging-based texture analysis (MRI-TA) in differentiating between benign and borderline/malignant PTs. Methods: Forty-three women with 44 histologically proven PTs underwent breast MRI before surgery and were classified into benign (n = 26) and borderline/malignant groups (n = 18 [15 borderline, 3 malignant]). Clinical and routine MRI parameters (CRMP) and MRI-TA were used to distinguish benign from borderline/malignant PT. In total, 298 texture parameters were extracted from fat-suppression (FS) T2-weighted, FS unenhanced T1-weighted, and FS first-enhanced T1-weighted sequences. To evaluate the diagnostic performance, receiver operating characteristic curve analysis was performed for the K-nearest neighbor classifier trained with significantly different parameters of CRMP, MRI sequence-based TA, and the combination strategy. Results: Compared with benign PTs, borderline/malignant ones presented a higher local recurrence (p = 0.045); larger size (p < 0.001); different time-intensity curve pattern (p = 0.010); and higher frequency of strong lobulation (p = 0.024), septation enhancement (p = 0.048), cystic component (p = 0.023), and irregular cystic wall (p = 0.045). TA of FS T2-weighted images (0.86) showed a significantly higher area under the curve (AUC) than that of FS unenhanced T1-weighted (0.65, p = 0.010) or first-enhanced phase (0.72, p = 0.049) images. The texture parameters of FS T2-weighted sequences tended to have a higher AUC than CRMP (0.79, p = 0.404). Additionally, the combination strategy exhibited a similar AUC (0.89, p = 0.622) in comparison with the texture parameters of FS T2-weighted sequences. Conclusion MRI-TA demonstrated good predictive performance for breast PT pathological grading and could provide surgical planning guidance. Clinical data and routine MRI features were also valuable for grading PTs.

Objective:To investigate the effects and mechanism of copper oxide nanozymes on wound healing of full-thickness skin defects in diabetic mice.Methods:(1) Copper oxide nanozymes were synthesized through the reaction of copper chloride and L-ascorbic acid. Transmission electron microscope was used for observing the particle size and morphology of copper oxide nanozymes, and dynamic light scattering particle size analyzers and Zeta potentiometer were used to analyze the hydrated particle size and surface potential of copper oxide nanozymes, respectively. (2) The hydrogen peroxide detection kit, superoxide anion determination kit, and 3, 3′, 5, 5′-tetramethylbenzidine were used to test the hydrogen peroxide, superoxide anion, and hydroxyl radicals scavenging ability of 150 ng/mL copper oxide nanozymes, respectively, and the scavenging proportions of hydrogen peroxide, superoxide anion, and hydroxyl radicals were calculated. The sample numbers were all 3. (3) Mouse fibroblast cell line 3T3 cells were divided into blank control group, simple hydrogen peroxide group, and hydrogen peroxide+ copper oxide group according to the random number table (the same grouping method below), with 3 wells in each group. Cells in hydrogen peroxide+ copper oxide group were pre-treated with copper oxide nanozymes in final mass concentration of 25 ng/mL for 30 minutes, and then hydrogen peroxide in final molarity of 250 μmol/L was added into simple hydrogen peroxide group and hydrogen peroxide+ copper oxide group. Cells in blank control group were routinely cultured. After 24 hours of culture, 2′, 7′-dichlorodihydrofluorescein diacetate fluorescence probe was used to detect the level of reactive oxygen species (indicated by green fluorescence intensity) in cells and cell counting kit-8 assay was performed to detect and calculate the cell survival rate. (4) Ten male BALB/c mice aged 6-8 weeks (the same gender and age below) were divided into phosphate buffer saline (PBS) group and copper oxide group, with 5 mice in each group. The mice in the copper oxide group were injected with 800 ng/kg copper oxide nanozyme at a concentration of 200 ng/mL via the caudal vein, and the mice in PBS group were treated with the same volume of PBS. The mice in the two groups were treated once a day for seven consecutive days. On the eighth day, 5 mice from each group were conducted and blood samples were taken for analysis of blood panel and serum biochemistry, and then the heart, liver, spleen, lung, and kidney were harvested for histopathological observation by hematoxylin-eosin (HE) staining after the mice were sacrificed. (5) Twenty mice were divided into PBS group and copper oxide group, with 10 mice in each group. Diabetes was induced by streptozotocin and high-sugar and high-fat diet and a full-thickness skin defect wound with diameter of 6 mm was reproduced on the back of each diabetic mouse. Immediately after injury, 20 μL PBS and 20 μL copper oxide nanozymes at the concentration of 200 ng/mL were added respectively to the wounds of mice in PBS group and copper oxide group, with the treatment being continued for twelve consecutive days. Three mice were selected from each group, and the wound healing was observed on post injury day (PID) 0 (immediately), 3, 6, 9, and 12 and the un-healed area was calculated. On PID 6, three mice from each group that were not for wound observation were sacrificed, and the content of interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6 in the wound tissue were determined by enzyme-linked immunosorbent assay. On PID 12, the rest 7 mice in each group were sacrificed for observation of the length of regenerated epidermis in wound tissue by HE staining, and the level of reactive oxygen species (indicated as red fluorescence intensity) in wound tissue by dihydroethidium staining. Data were statistically analyzed with one-way analysis of variance, analysis of variance for repeated measurement, independent sample t test, and Bonferroni test. Results:(1) The prepared copper oxide nanozymes were uniform in size with an average diameter of 3.5-4.0 nm in dry state, the hydrated particle size of 4.5 nm, and the surface potential of (-9.8±0.3) mV. By comprehensive judgment, copper oxide nanozymes had been successfully prepared. (2) After being treated with copper oxide nanozyme for 2 hours, 10 minutes, and 5 minutes, respectively, the scavenging proportions of hydrogen peroxide, superoxide anion, and hydroxyl radicals were (77±5)%, (45±5)%, and (84±4)%, respectively. (3) After 24 hours of culture, the cells in simple hydrogen peroxide group showed a significantly increased level of reactive oxygen species with abnormal morphology and decrease in cell number, while the cells in hydrogen peroxide+ copper oxide group showed a remarkably decreased level of reactive oxygen species with normal morphology similar to that of blank control group. The cell survival rate in simple hydrogen peroxide group was obviously reduced compared with the rates in blank control group and hydrogen peroxide+ copper oxide group ( P<0.01), while there was no significant difference in cell survival rate between hydrogen peroxide+ copper oxide group and blank control group. (4) After 7 days of injection, there were no obvious differences in liver and kidney function indexes and blood panel indexes between mice in PBS group and copper oxide group. No necrosis, hyperaemia or hemorrhage in heart, liver, spleen, lung, or kidney was observed in mice in copper oxide group, which was similar to that in PBS group. (5) Compared with that of PBS group, wounds of mice in copper oxide group showed an accelerated healing trend with less redness. On PID 6, 9, and 12, the areas of un-healed wound of mice in copper oxide group (28.8±1.9), (17.6±3.8), and (10.4±1.8) mm 2, respectively, significantly lower than (38.0±4.3), (30.2±3.0), and (24.2±3.0) mm 2 in PBS group ( t=3.706, 5.075, 5.558, P<0.01). On PID 6, the content of IL-1β, TNF-α, and IL-6 in wounds of mice in copper oxide group were significantly lower than that in PBS group ( t=6.115, 11.762, 11.725, P<0.01). On PID 12, the length of regenerated epidermis in wounds of mice in copper oxide group was obviously longer than that in PBS group, the level of reactive oxygen species in wounds of mice in copper oxide group was obviously lower than that in PBS group. Conclusions:Copper oxide nanozyme not only has good biocompatibility, but also has efficient reactive oxygen species scavenging activity. It can eliminate the over-expressed reactive oxygen species in the full-thickness defect wounds of diabetic mice, reduce oxidative stress and inflammation, thus promoting wound repair.

The combination of diagnosis and treatment through nanotechnology is conducive to the development of cancer treatment. Fluorescent imaging in the second near-infrared window(NIR-II)developed rapidly in recent years due to its imaging advantages. In this paper, we prepared a novel nano drug system, DOX-IR1061-cationic liposome, in which NIR-II fluorescent probe IR1061 was loaded as imaging agents and doxorubicin was loaded as therapeutic agents. It also explores enhanced cellular uptake and cancer cell inhibition rate through octadecylamine. Our NIR-II performance test on liposomes showed that DOX-IR1061-cationic liposome has NIR-II imaging ability. Analysis of liposome cell uptake behavior and cancer cell inhibition experiments demonstrated that octadecylamine can promote liposome uptake by cells and synergize with DOX to enhance anticancer effects. This suggests that the DOX-IR1061-cationic liposome can be used to achieve imaging and therapy effect with further research value.