OBJECTIVE To investigate the effect of bs-5-YHEDA iron chelating peptide combined with semaglutide on the cognitive ability and pathological characteristics of D-Gal-induced Alzheimer's disease(AD) model mice. METHODS Forty mice were randomly divided into 5 groups, namely the healthy control group, PBS group, bs-5-YHEDA iron chelating peptide group, combined treatment group and positive control group, with 8 mice in each group, half of each sex. Except for the healthy control group, D-galactose was injected to induce the AD mice model for 6 weeks. For 3 consecutive weeks starting from the 4th week, the bs-5-YHEDA iron chelating peptide group was injected with bs-5-YHEDA(1 mg·mL–1) once every other day at 200 µL in the tail vein; the bs-5-YHEDA iron chelating peptide(1 mg·mL–1) and semaglutide(25 nmol·kg–1·d–1) were given alternately once a day in the combination treatment group; the positive control group was given memantine(3.3 mg·kg–1·d–1) by gavage every other day. The healthy control group and PBS group were injected with the equal dose of PBS. At the end of treatment, the learning memory ability of mice was detected by the Morris water maze method, whole brain and whole blood were dissected, and pathological changes in hippocampal region were observed by HE staining, and Aβ expression and Tau protein phosphorylation levels were detected by immunohistochemistry, enzyme-linked immunosorbent assay and immunoblotting. RESULTS In the Morris water maze spatial exploration experiment, the differences in the number of times the mice traversed the platform, the ratio of swimming distance to the target quadrant, and the time ratio were statistically significant in each group(P<0.05); compared with the PBS group, the ratio of swimming distance to the target quadrant increased in the combined treatment group, and the differences were statistically significant(P<0.05). The results of HE staining showed that compared with the healthy control mice, the hippocampal area in the PBS group showed reduced levels of pyramidal cells, disorganized arrangement, cell edema, and deep staining of nuclei consolidation. Cellular disorganization, deep staining of nuclei and apoptosis in the hippocampus were significantly improved in each treatment group after drug treatment. Immunohistochemistry and Western blotting results showed that the Aβ expression levels and Tau protein phosphorylation levels were significantly higher in the PBS-administered mice compared with the healthy control mice, and the Aβ expression levels and Tau protein phosphorylation levels were reduced in each group after drug treatment, with statistically significant differences(P<0.01 or P<0.001 ). CONCLUSION The combination of bs-5-YHEDA iron chelating peptide and semaglutide can effectively improve the learning and memory ability and pathological characteristics of AD mice, but from the results of immunohistochemistry and immunoblotting experiments, the improvement of pathological characteristics of AD mice in the combination treatment group is not obvious compared with the single bs-5-YHEDA iron chelating peptide group, suggesting that there may be a threshold effect of our designed dual-target combination treatment on the cognitive improvement of AD mice, and the optimization and validation of the effect of multi-target combination treatment need further study.

Objective:To investigate the mechanism of immunomodulatory effects of umbilical cord mesenchymal stem cells(UC-MSCs)modified by miR-125b-5p on systemic lupus erythematosus(SLE).Methods:The expression level of miR-125b-5p was detected by real-time fluorescence quantitative PCR in UC-MSCs and peripheral blood mononuclear cells(PBMCs)from SLE patients and health checkers.Annexin V-FITC/PI apoptosis detection kit was used to detect the effect of miR-125b-5p on apoptosis of UC-MSCs.MRL/lpr mice in each group were injected with UC-MSCs via tail vein,and T-lymphocyte subsets in the spleen of the MRL/lpr mice were detected by flow cytometry after 5 weeks.The expression levels of interleukin(IL)-4 and IL-17A in serum of MRL/lpr mice were detected by ELISA.Hematoxylin-eosin staining was used to observe the pathological manifestations of the lungs and kidneys of the MRL/lpr mice.Results:miR-125b-5p was significantly down-regulated in PBMCs of SLE patients compared with healthy controls(P＜0.01).Compared with the UC-MSCs group,the expression of miR-125b-5p in UC-MSCs modified by miR-125b-5p group was increased(P＜0.01).The survival rate of UC-MSCs was significantly increased by miR-125b-5p(P＜0.01).Compared with the untreated group of MRL/lpr mice,the expression level of IL-4 in serum was increased(P＜0.05);the expression level of IL-17A was decreased(P＜0.05);the proportion of Th17 cells in the spleen of MRL/lpr mice was decreased(P＜0.05);the inflammatory cells infiltration and micro-thrombosis of lungs and kidneys of MRL/lpr mice were significantly reduced in the UC-MSCs modified by miR-125b-5p treatment group.Conclusion:UC-MSCs modified by miR-125b-5p have immunomodulatory effects on systemic lupus erythematosus.

Objective : To investigate the imunomodulatory effects of umbilical cord mesenchymal stem cells(UC⁃MSCs) modified by miR⁃125b⁃5p through JAK2/STAT3 pathway on systemic lupus erythematosus(SLE) . Methods: UC⁃MSCs were isolated and cultured under aseptic conditions ; Peripheral blood mononuclear cells ( PBMCs)were separated from SLE patients by density gradient centrifugation. The relative expressions of IL⁃17A , Foxp3 ,IFN⁃γ , IL⁃4 genes in PBMCs cultured with UC⁃MSCs for 48 h were detected by RT⁃qPCR; The relative expressions of JAK2 , p ⁃JAK2 , STAT3 , p ⁃STAT3 and IL⁃18 proteins in kidney tissues of MRL/lpr mice were detected by west⁃ern blot. Results : Compared with the PBMCs culture group , the expression of IFN⁃γ and IL⁃17A and the propor⁃tion of Th17/Treg cells were significantly down⁃regulated in UC⁃MSCs + miR⁃125b⁃5p group , UC⁃MSCs + miR⁃NC group and UC⁃MSCs group(P < 0. 01) , the expression of the proportion of Th1/Th2 cells (P < 0. 05) was down⁃regulated in UC⁃MSCs + miR⁃125b⁃5p group and UC⁃MSCs + miR⁃NC group ; Compared with the untreated group of MRL/lpr mice , the relative expressions of JAK2 , p ⁃JAK2 , STAT3 , p ⁃STAT3 and IL⁃18 proteins in kidney tissues of MRL/lpr mice were significantly down⁃regulated in UC⁃MSCs + miR⁃125b⁃5p group (P < 0. 01) , and the rela⁃tive expressions of IL⁃18 proteins was significantly down⁃regulated in UC⁃MSCs + miR⁃NC group and UC⁃MSCs group (P < 0. 01) . Conclusion miR⁃125b⁃5p plays a synergistic role in UC⁃MSCs ,which regulates the differenti⁃ation of Th2 cells in PBMCs of SLE patients and the relative expressions of p ⁃JAK2/JAK2 , p ⁃STAT3/STAT3 , and IL⁃18 proteins in kidney tissues of MRL/lpr mice. UC⁃MSCs modified by miR⁃125b⁃5p may play immunomodulato⁃ry effect on SLE by JAK2/STAT3 signaling pathway.

OBJECTIVES: This study evaluated the prognostic power of serum uric acid (UA) in predicting adverse events in elderly acute coronary syndrome (ACS) patients with diabetes mellitus (DM). METHODS: The analysis involved 718 ACS patients ‍>80 years old whose general clinical data and baseline blood biochemical indicators were collected prospectively from January 2006 to December 2012. These patients were classified into two groups based on DM status, and then followed up after discharge. The Kaplan-Meier method was used for major adverse cardiac event (MACE) rates and all-cause mortality. Multivariate Cox regression was performed to analyze the relationship between UA level and long-term clinical prognosis. Receiver operating characteristic (ROC) curves were analyzed to predict the cutoff value of UA in elderly ACS patients with DM. There were 242 and 476 patients in the DM and non-DM (NDM) groups, respectively, and the follow-up time after discharge was 40‒120 months (median, 63 months; interquartile range, 51‒74 months). RESULTS: The all-cause mortality, cardiac mortality, and MACE rates in both DM and NDM patients were higher than those in the control group ( CONCLUSIONS Serum UA level is a strong independent predictor of long-term all-cause death and MACE in elderly ACS patients with DM.

Objective:To investigate the clinical effect of myocutaneous flap combined with antibiotic-loaded polymethylmethacrylate (PMMA) cement in the treatment of Cierny-Mader type III-IV osteomyelitis.Methods:From April, 2014 to March, 2019, 53 patients with Cierny-Mader type III-IV chronic osteomyelitis were treated with myocutaneous flap combined with antibiotic-loaded PMMA cement. There were 33 males and 20 females, with an average age of (52.2±3.0) (29-78) years old. The area of the wound ranged from 2.0 cm×2.0 cm to 14.0 cm×28.0 cm. All flaps were closed directly. There were 23 patients who were removed the cement at 3 months after surgery, and the other 30 were not. After the surgery, the blood supply of the flap, the effusion of the wound, the complications of the donor area, signs of fresh bone destruction on X-ray and the color, the texture and scar of the flap were observed in the follow-up at the clinic.Results:Forty-nine cases healed in one stage, and 4 had delayed healing. Postoperative vascular crisis occurred in 6 cases and releasesd by prompt surgical exploration. The patients were followed-up for 0.6-3.0 years, with an average of 18 months. All 53 myocutaneous flaps completely survived ultimately. The color of flaps was similar to the recipient areas, and the flaps were smooth and soft and satisfactory in appearance. During the follow-up period, X-ray examination showed no sign of fresh bone destruction. Osteomyelitis was significantly controlled. There was no inflammation reaction such as swelling, pain, ulceration and effusion of the flaps, and there was no recurrence of osteomyelitis. All donor areas healed primarily.Conclusion:Myocutaneous flap combined with antibiotic-loaded PMMA cement has achieved good anti-infection effects in satisfactory results, less postoperative complications and low recurrence rate in the treatment of Cierny-Mader type III-IV osteomyelitis. Application and promotion of such technique would deliver good benefits.

Objective To quantitatively explore the influence of knife sharpness on forearm wounds in knife slash cases. Methods The finite element models of the upper limb and knives with 3 degrees of sharpness (with sharp blade, blunt blade, wide blade) were developed based on human CT images and prototype of slash knife. The slash by 3 kinds of knives on the forearm at velocity of 4 m/s and duration of 10 ms was simulated, so as to analyze changes in contact forces, wound dimensions and energy. Results During the slash by knives with sharp, blunt, wide blade, the blades reached the ulna at about 65, 85, 95 ms, respectively. The corresponding slash forces were 846, 1 064 and 1 865 N; the wound lengths were 135.64, 105.47 and 99.23 mm; the wound depths were 38.77, 27.81 and 18.74 mm. With the sharpness of blade decreasing, the wound formation was slowed, the length and depth decreased and the slash force increased. The model system for slash knife with sharp blade had obviously greater total energy and inner energy, but smaller kinetic energy, compared with slash knife with blunt blade and wide blade. Conclusions The method for quantitatively assessing wound formation in knife slash upon the forearm was developed. The research findings deepen the understanding of biomechanical mechanism of wound formation by knife slash, and provide new scientific means for forensic investigation and court trial of knife slash cases.

Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Humans ; Lymphoma, Follicular ; drug therapy ; Rituximab

OBJECTIVEA prospective, multicenter and non-interventional prospective study was conducted to evaluate the clinical features of rituximab combined with chemotherapy (R-Chemo) as first-line treatment on newly diagnosed Chinese patients with diffuse large B-cell lymphoma (DLBCL).

METHODSThis was a single arm, prospective, observational multicenter and phase IV clinical trial for 279 patients, who were newly diagnosed as CD20-positive DLBCL from 24 medical centers in China 2011 and 2012, no special exclusion criteria were used. All patients received rituximab based R-Chemo regimes, such as R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisolone) and other regimes as the first-line treatment. The treatment strategies were determined by physicians and patients without detailed description for treatment course, dose, interval time and examination. Clinical response and safety of all patients were investigated in 120 days after completion of last dose of rituximab.

RESULTSOf 279 patients, 258 with stage I-IV who received at least 1 cycle of rituximab treatment and completed at least one time of tumor assessment were enrolled into intention-to-treat analysis, including 148 male and 110 female. The median age of all patients was 57.2(12.8-88.4) years. ECOG performance statuses of 0 or 1 were observed in 91.1% of patients, international prognostic index levels in the low-risk and low-middle-risk groups in 76.4% of patients, the tumor diameters smaller than 7.5 cm in 69.0% of patients. All patients received 6 median cycles of R-Chemo treatment every 24.4 days. R-CHOP treatment was shown to improve the clinical response with overall response rates of 94.2%. Common adverse events included anemia, marrow failure, leukopenia, thrombocytopenia, digestive diseases, infection and liver toxicity. All adverse events are manageable.

CONCLUSIONNon-interventional clinical trial of R-Chemo remains the standard first-line treatment for newly diagnosed patients with DLBCL in real clinical practice, which is consistent with international treatment recommendations for DLBCL patients. R-Chemo can provide the clinical evidence and benefit as the first-line standard treatment for Chinese patients with DLBCL.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Male ; Middle Aged ; Prospective Studies ; Rituximab ; Treatment Outcome

Background and objective Afatinib is an irreversible ErbB-family blocker with a clinical activity in non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations. hTe aim of this study is to assess the safety of afatinib in patients with advanced lung adenocarcinoma. Methods Patients with lung adenocarcinoma (stage IIIb or IV) with EGFR mutations were ifrst-line treated with an oral administration of afatinib (40 mg/d) until disease progression. Adverse events, effects, and survival condition were observed. Results hTe most common adverse events were diarrhea (n=5, 100%), skin rash (n=4, 80%), and mucositis/stomatitis (n=4, 80%). Moderate toxicities not exceeding grade 3 were observed. Relatively, the most serious adverse reaction was mucositis/stomatitis. Mild diarrhea occurred in all patients. hTree patients experienced temporary drug withdrawal and dose reduction because of adverse reaction. Among the four patients who were evaluated, partial response was observed in two patients (50%), one with stable disease (25%) and one with progressive disease (25%). Median progression-free survival was 9.7 months, whereas median overall survival was 18.4 months. Conclusion Afa-tinib was approved as ifrst-line treatment for patients with advanced lung adenocarcinoma. hTe most common adverse events were diarrhea and skin rash. However, mucositis/stomatitis related to afatinib should also be considered. Considering the small number of cases, the conclusion requires more trials for conifrmation.

Objective To assess the variation of salivary gland function in differentiated thyroid carcinoma (DTC) patients receiving different doses of 131 I therapy in the first.Methods 40 DTC patients were divided into two groups according to the application 131I doses,salivary scintigraphy was performed with 99TcmO4-on DTC patients before and 3months after 131 I therapy.Quantitative analysis of salivary gland function were performed.Results In low dose group,only the uptake ratio of 30min (UR30) of bilateral parotid decreased ( P ＜ 0.05 ) ; but in high - dose group,the uptake ratio of 30min (UR30),excretion fraction ( EF ),excretion rate (ER) of bilateral parotid and submandibular glands were significantly decreased,excretion time(EP) significantly prolonged after 131 I therapy( all P ＜0.05) ;the parotid gland was more severely than the submandibular gland.Conclusion Salivary gland function was damaged of DTC patients receiving different doses of 131I therapy in the first,salivary gland dysfunction correlated well with the administered dose.