ObjectiveTo investigate the influence of empagliflozin combined with donafenib or lenvatinib on the pharmacokinetic parameters of each drug， and to provide a reference for combined medication in clinical practice. MethodsA total of 48 healthy male Sprague-Dawley rats were divided into 8 groups： empagliflozin group 1 and 2， donafenib group， lenvatinib group， donafenib pretreatment+empagliflozin group， lenvatinib pretreatment + empagliflozin group， empagliflozin pretreatment+donafenib group， and empagliflozin pretreatment+lenvatinib group， with 6 rats in each group. The doses of empagliflozin， donafenib， and lenvatinib were 2.5 mg/kg， 40 mg/kg， and 1.2 mg/kg， respectively. The rats in the empagliflozin group， donafenib group， and lenvatinib group were given a blank solvent by gavage for 7 consecutive days， followed by a single dose of empagliflozin， donafenib， or lenvatinib on day 7 after the administration of the blank solvent； the rats in the pretreatment groups were given the pretreatment drug by gavage for 7 consecutive days， followed by a single dose of drug combination on day 7 after administration of the pretreatment drug. Blood samples were collected at different time points， and plasma was separated to measure the concentration of each drug. A validated ultra-performance liquid chromatography-tandem mass spectrometry method was used to measure the plasma concentrations of donafenib， lenvatinib， and empagliflozin， and a non-compartmental model was used to calculate the main pharmacokinetic parameters of each drug （area under the plasma concentration-time curve ［AUC］， time to peak ［T_max］， peak concentration ［C_max］， and half-life time ［t_1/2］）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with the empagliflozin group， the donafenib pretreatment+empagliflozin group had significant increases in the AUC_0-t and AUC_0-∞ of empagliflozin （P=0.011 and 0.008）， while the lenvatinib pretreatment+empagliflozin group had no significant change in the AUC of empagliflozin， with a slightly shorter T_max （P=0.019）. Compared with the donafenib group， the empagliflozin pretreatment+donafenib group had significant increases in the AUC_0-t and AUC_0-∞ of donafenib （P=0.027 and 0.025）， as well as a significant increase in C_max （P=0.015） and significant reductions in CLz/F and Vz/F （P=0.005 and 0.004）； compared with the lenvatinib group， the empagliflozin pretreatment+lenvatinib group had a reduction in the t_1/2 of lenvatinib by approximately 5 hours （P=0.002）， with a trend of reduction in AUC_0-t （P0.05）. ConclusionEmpagliflozin combined with donafenib may alter the pharmacokinetic parameters of both drugs， leading to a significant increase in the exposure levels of both drugs， and efficacy and adverse reactions should be monitored during co-administration. There are no significant changes in the exposure levels of empagliflozin and lenvatinib during co-administration.

With the further increase of the global cancer burden, various cancers are increasingly challenging human health status and quality of life. Thus, early screening of cancer is crucial. Urinary volatile organic compounds (VOCs) detection techniques have the advantages of easy access to samples, high acceptance of patients, non-invasive, and so on, which have been favored and concerned by researchers. In this paper, existing techniques and methods for cancer diagnosis based on urine VOCs were described, relevant studies on the use of urine VOCs for cancer diagnosis were reviewed, and the barriers and future perspectives of the technique were discussed. This paper can be a reference for researchers working in the direction of urinary VOCs detection, a multidisciplinary field that spans medicine and materials science.

Objective:To explore the clinical features and survival of newly diagnosed follicular lymphoma (FL) patients with diffuse large B-cell lymphoma (DLBCL) component.Methods:1845 newly diagnosed FL patients aged ≥ 18 years with grades 1-3a in 11 medical centers in China from 2000 to 2020 were included, and patients with DLBCL component were screened. The clinical data and survival data of the patients were retrospectively analyzed, and the prognostic factors were screened by univariate and multivariate analysis.Results:146 patients (7.9% ) with newly diagnosed FL had DLBCL component. The median age was 56 (25-83) years, 79 males (54.1% ) . The pathology of 127 patients showed the proportion of DLBCL component. Patients were divided into two groups according to whether the proportion of DLBCL component was ≥ 50% . The study found that patients with DLBCL component ≥ 50% had higher grade 3 ratio (94.3% vs 91.9% , P=0.010) , Ki-67 index ≥ 70% ratio (58.5% vs 32.9% , P=0.013) and PET-CT SUVmax ≥ 13 ratio (72.4% vs 46.3% , P=0.030) than patients with DLBCL component<50% . All patients received CHOP or CHOP like ± rituximab chemotherapy. The overall response rate (ORR) was 88.2% , and the complete response (CR) rate was 76.4% . In the groups with different proportions of DLBCL component, there was no significant difference in the remission rate after induction treatment and the incidence of disease progression within 2 years after initiation of treatment (POD24) ( P<0.05) . The overall estimated 5-year progression free survival (PFS) rate was 58.9% , and the 5-year overall survival (OS) rate was 90.4% . The 5-year OS rate of POD24 patients was lower than that of non POD24 patients (70.3% vs 98.5% , P<0.001) . Compared with non maintenance treatment of rituximab, maintenance treatment of rituximab could not benefit the 5-year PFS rate (57.7% vs 58.8% , P=0.543) , and the 5-year OS rate had a benefit trend, but the difference was not statistically significant (100% vs 87.8% , P=0.082) . Multivariate analysis showed that failure to reach CR after induction treatment was an independent risk factor for PFS ( P=0.006) , while LDH higher than normal was an independent risk factor for OS ( P=0.031) . Conclusion:FL patients with DLBCL component ≥50% have more invasive clinical and pathological features. CHOP/CHOP like ± rituximab regimen can improve the clinical efficacy of patients. Rituximab maintenance therapy can not benefit the PFS and OS of patients. Failure to reach CR after induction therapy was the independent unfavorable factor for PFS.

Objective With the help of computerized tomography (CT) and susceptibility-weighted imaging (SWI) examinations, to analyze and compare the incidence and the prevalent sites of microbleeds (CMBs) in control group, diabetes group, hypertension group and diabetic hypertension group with intracerebral CMBs. The risk factors for the onset of CMBs also will be explored, in order to provide a basis for the selection of clinical diagnosis and treatment options for CMBs. Methods A collection of 174 non-acute patients in the Department of Neurology of Shandong Electric Power Central Hospital from May 2019 to October 2020, including 101 males and 73 females, aged 45-89 years, with an average age of 72 ± 5 years. Divided into four groups according to disease types: Hypertension with type 2 diabetes group, Hypertension group, Type 2 diabetes group, Control group (no hypertension and type 2 diabetes). All patients underwent CT and MRI SWI sequence scans. The 4 groups of patients were matched in terms of gender and age, excluding the influence of gender and age. The incidence, number and distribution of CMBs in the four groups were counted, and the CT and SWI imaging manifestations of CMBs in the four groups were analyzed and compared. Results CT did not find the incidence of CMBs in the brain of patients. SWI imaging showed that CMBs were detected in 58 of 174 patients (incidence rate 33.3%), and CMBs occurred in 24 cases of diabetes and hypertension group (incidence rate 57.1%). CMBs occurred in 21 cases in the hypertension group (incidence rate 46.7%), 8 cases in the diabetes group (incidence rate 22.2%), and CMBs occurred in 5 cases in the control group (incidence rate 9.8%). The incidence of CMBs in the hypertension group and the diabetes combined with hypertension group was significantly higher than that in the control group (P < 0.05). There was no significant difference in the incidence of CMBs in patients with simple diabetes compared with the control group. Also, there was no significant difference in the incidence of CMBs between the diabetes combined with hypertension group and the simple hypertension group. Conclusion CT did not find the incidence of CMBs in the brains of patients in the non-acute phase. SWI could clearly show the CMBs of the enrolled patients. Diabetes is less likely to cause an increase in CMBs. Hypertension is significantly related to the occurrence of CMBs. CMBs associated with hypertension or/and diabetes are common in the basal ganglia and thalamus, which is different from cerebral amyloid angiopathy, which provides a basis for the choice of clinical treatment options.

Osteosarcoma needs to continuously induce angiogenesis to satisfy its own nutritional supply in the process of development. Therefore, the inhibition of osteosarcoma cell-induced angiogenesis as a target has become a research hot in recent years. Currently, vascular inhibitors targeting mRNA-encoded protein have been applied in clinic, but the efficacy is poor. Non-coding RNA (ncRNA) is a type of RNA molecules that do not participate in protein coding. ncRNA can regulate the angiogenesis of osteosarcoma by regulating the secretion of vascular factors such as vascular endothelial growth factor, angiogenin-2 and hypoxia-inducible factor 1 or the interaction between ncRNAs. This article reviews the role of ncRNA in the angiogenesis of osteosarcoma to provide references for clinical targeted therapy strategies for osteosarcoma.

Objective:To investigate the effects of hydrogen rich-saline (HRS) on intestinal mucosal barrier in rat with intestinal ischemia/reperfusion injury (IIRI).Methods:Twenty-four healthy male Sprague-Dawley rats, aged 8 weeks, were randomly divided into 3 groups (8 in each group) by random number table method: sham group, model group and HRS group.Rats in HRS group were intraperitoneally injected with HRS (10 mL/kg) at 30 min of ischemia, and the same amount of normal saline was intraperitoneally injected in model group.After 45 min of ischemia and 6 h of reperfusion, rats were sacrificed.Serum and ileum were collected for further detection.Tumor necrosis factor alpha (TNF-α), interleukin (IL)- 1β and IL-17A expression levels in serum were detected by conducting enzyme-linked immunosorbent assay (ELISA). The localization expressions of tight junction protein Occludin was detected by immunohistochemical staining (IHC), while the localization expression of tight junction protein zonula occluden-1 (ZO-1) were detected by immunofluorescence staining (IF). The protein expression of Occludin, ZO-1, and Lysozyme were detected by performing Western blot.The mRNA expression of Lysozyme and α-defensin were detected by real-time PCR (qPCR).Results:ELISA results proved that the levels of serum TNF-α and IL-1β in HRS group rats were significantly lower than those in model group [(62.02±29.97) ng/L vs.(113.40±44.58) ng/L, (21.68±0.35) ng/L vs.(28.29±3.49) ng/L], while the level of IL-17A increased [(28.18±5.28) ng/L vs. (15.10±3.60) ng/L] (all P<0.05). IHC staining: compared with model group, the expression of Occludin in HRS group was uniform and continuous, and the staining was darker.IF results: compared with model group, the fluorescence signal intensity of ZO-1 in HRS group rats significantly increased, and the distribution was clear and continuous.Wes-tern blot results: compared with model group, the expression levels of Occludin and ZO-1 proteins in HRS group rats remarkably increased (0.79±0.06 vs. 0.54±0.04, 0.91±0.11 vs. 0.51±0.13), while Lysozyme protein decreased (1.50±0.40 vs. 2.99±0.80) (all P<0.05). qPCR results revealed that the expression level of Lysozyme mRNA in HRS group rats was lower than that in model group (1.64±0.33 vs. 2.20±0.40), while α-defensin mRNA obviously increased (0.82±0.19 vs. 0.47±0.13) (all P<0.01). Conclusions:HRS protects intestinal mucosal barrier by inhibiting the expression of tight junctions and the secretion of antimicrobial peptides in rat suffering from IIRI.

COVID-19 is a public health emergency currently. In this study, a scale-free network model is established based on the Spring Migration data in 2020.The cities is clustered into three different modules. The epidemic of the cities in the black module was the most serious, followed by the red and the cyan. The black module contains 9 cities in Zhejiang province and 8 cities in Guangdong province, most of them located in the southeast coastal economic belt. These cities should be the key cities for epidemic prevention and control.

COVID-19 is a public health emergency currently. In this study, a scale-free network model is established based on the Spring Migration data in 2020.The cities is clustered into three different modules. The epidemic of the cities in the black module was the most serious, followed by the red and the cyan. The black module contains 9 cities in Zhejiang province and 8 cities in Guangdong province, most of them located in the southeast coastal economic belt. These cities should be the key cities for epidemic prevention and control.

Objective To evaluate the cost-effectiveness of two chemotherapy regimens in NSCLC for the purpose of lower cost,higher quality medical care.Methods 56 patients with advanced NSCLC were divided into two groups from our hospital,group PP(pemtrexal+cisplatin,n=30)and group GP(gemcitabine+cisplatin,n=26),and analyzed by pharmaco-economic cost-effectiveness method,and retrospective analysis was also applied.Results Effective rates of two regimens were 46.67%,42.31%,no significant difference.But there was significant difference in the incidence rate of ADR between the two groups.The cost of chemotherapy regiments were 31 985.48 and 27 683.15 yuan.The average length of stay was 10.94 and 13·91 days.Compared to group GP,for each unit of efficacy,the cost in group PP were increased 986.77 yuan.Conclusion From the analysis of cost-effectiveness,group PP had higher chemotherapy costs,but better safety than group GP.

Objective To investigate the effect of the tibiofemoral joint surface with high conformity on total knee prosthesis motion and insert wear. Methods A type of knee prosthesis with a high coronal conformity was designed and manufactured, and its insert wear was studied by in vitro wear testing combined with finite element simulation. ResultsThe mass wear rates calculated by the in vitro wear testing and finite element simulation were (14.29±3.19) mg/MC and 14.67 mg/MC (MC, million cycle), respectively. After five MCs, the areas of the insert wear obtained by both the methods were basically consistent, and severe wear was found to occur in the middle part of the insert. ConclusionsThe result of the finite element simulation coincided with that of the in vitro testing. The wear rate of the tibiofemoral joint surface of the total knee prosthesis with a high coronal conformity was relatively low. The research outcomes have practical significance for the evaluation and clinical application of the total knee prosthesis with a high conformity.