Objective To establish the drug use evaluation(DUE)criteria of recombinant human prourokinase(rhPro-UK),and to provide reference for the rational clinical application of rhPro-UK.Methods Based on the drug instructions of rhPro-UK,DUE standard rules were established by referring to relevant guidelines,expert consensus,authoritative literature and expert consultation.The medical records of hospitalized patients treated with rhPro-UK from January 2019 to May 2022 in Xilin Gol League Central Hospital were evaluated by retrospective investigation.The effectiveness of rhPro-UK was evaluated based on clinical outcome,and its safety was evaluated based on the incidence and severity of adverse reactions.Results A total of 230 cases were included,and 4 cases fully met the evaluation criteria(medication indication,medication process,medication results),accounting for 1.74％.There were 226 patients(98.26％)with irrational drug use,mainly manifested in two aspects of drug indication and drug process(administration mode and dosage).Treatment was effective in 221 patients,with an overall effective rate of 96.09％;139 patients experienced adverse reactions,with an incidence rate of 60.43％.Conclusion The clinical use of rhPro-UK in our hospital is irrational in the indication of medication and the process of medication,and the establishment of the DUE standard rules of rhPro-UK can provide a reference to standardize the clinical application of rhPro-UK and promote its rational use.

Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.

Adenocarcinoma, Clear Cell/pathology* ; Carcinoma in Situ ; Cell Transformation, Neoplastic ; China ; Endometriosis/pathology* ; Female ; Humans

Objective To investigate a reasonable threshold of total bilirubin for the diagnosis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), and to realize accurate early diagnosis. Methods A retrospective analysis was performed for the clinical data of 1232 patients with HBV-ACLF who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from September 2008 to September 2018, and according to the baseline serum level of total bilirubin (TBil), the patients were divided into group A (TBil < 205.2 μmol/L) and group B (TBil ≥205.2 μmol/L). the two groups were compared in terms of clinical features and 28-day, 90-day, 1-year, and 3-year survival. The t -test or the Mann-Whitney U rank sum test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to analyze survival rate, and the log-rank test was used for comparison. Results There were significant differences between the two groups in age( t =3.188, P =0.001) male sex( χ 2 =33.833, P < 0.001), liver failure classification( χ 2 =39.987, P < 0.001), white blood cell count( Z =6.586, P < 0.001), hemoglobin( Z =4.272, P < 0.001), platelet count( Z =3.680, P < 0.001), creatinine( Z =4.505, P < 0.001), total cholesterol( Z =8.644, P < 0.001), Na( Z =2.335, P =0.020), albumin( Z =2.592, P =0.010), HBV DNA( Z =3.703, P < 0.001), Model for End-Stage Liver Disease score( Z =11.828, P < 0.001), and MELD-Na score( Z =8.410, P < 0.001). At baseline, there were significant differences in the incidence rates of ascites and gastrointestinal bleeding between the two groups ( χ 2 =12.036、4.342, P < 0.05). Infection was the most common new-onset complication within 28 days, followed by hepatic encephalopathy, and there was a significant difference in the incidence rate of infection between the two groups ( χ 2 =5.294, P < 0.05). The 28-day transplant-free mortality rate was 21.2% in group A and 29.5% in group B( HR =1.473[95% CI : 1.151~1.886], P =0.005), which was consistent with the clinical feature of a high short-term mortality rate (> 15%) in patients with acute-on-chronic liver failure (ACLF). Although there was a difference in long-term mortality rate between the two groups, there was no significant increase in transplant-free mortality rate after 90 days in either group. Conclusion Under the premise of international normalized ratio ≥1.5, it is not recommended to increase the threshold of TBil to 205.2 μmol/L in the diagnostic criteria for HBV-ACLF, so as to ensure the early diagnosis of more ACLF patients and bring more opportunities for treatment and cure.

Objective:To assess the value of 18F-FDG PET/CT imaging and relevant factors in the interim therapeutic and prognostic evaluation of primary gastrointestinal lymphoma (PGIL) patients. Methods:From January 2008 to January 2018, 41 patients with B-cell PGIL (24 males, 17 females; age: 26-84 years) confirmed by pathology in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine were retrospectively included. 18F-FDG PET/CT was performed before chemotherapy and radiotherapy and after 3-4 courses of chemotherapy. There were 17 cases of mucosa-associated lymphoid tissue (MALT) lymphoma and 24 cases of diffuse large B-cell lymphoma (DLBCL). Mann-Whitney U test was used to compare the differences of metabolic parameters (SUV max, metabolic tumor volume (MTV), total lesion glycolysis (TLG)) before treatment between MALT lymphoma and DLBCL patients. ROC curve analysis was used to analyze the predictive abilities of different parameters for progression-free survival (PFS), and Cox regression analysis was used to analyze the influencing factors for PFS. Results:The median follow-up time of 41 patients was 25 (6-84) months, with the 3-year PFS rate of 55.9% and the overall survival (OS) rate of 80.2%. The baseline SUV max (23.2±11.9), MTV (260.7(66.2, 740.7) cm 3) and TLG (1 902.9(592.2, 8 418.1) g) in DLBCL were significantly higher than those in MALT lymphoma (7.9(6.2, 9.8), 45.9(28.4, 104.2) cm 3, 121.1(72.8, 295.6) g; z values: -4.02, -3.10, -3.92, all P<0.05). ΔSUV max in DLBCL patients (AUC=0.80, P=0.012), ΔSUV max% (AUC=0.89, P=0.007; AUC=0.80, P=0.012), ΔMTV%(AUC=0.91, P=0.005; AUC=0.77, P=0.026) and ΔTLG% (AUC=0.87, P=0.011; AUC=0.77, P=0.026) in MALT lymphoma and DLBCL patients before and after treatment were predictive factors of PFS. Multivariate analysis showed that ΔSUV max% was an independent factor for PFS of MALT lymphoma (hazard ratio ( HR)=17.192, 95% CI: 2.035-145.245, P=0.009), while ΔMTV% and ΔTLG% were factors for PFS of DLBCL (both HR=7.556, 95% CI: 1.968-29.016, P=0.003). Conclusions:There are significant differences in metabolic parameters between MALT lymphoma and DLBCL before treatment. Interim PET/CT is effective for the prediction of prognosis of MALT lymphoma and DLBCL.

This study aims at the critical role of P-glycoprotein (P-gp) in tumor drug resistance, taking advantage of the adenosine triphosphate (ATP) dependence of P-gp mediated drug transport and efflux across the cell membrane. Mitochondrial targeted calcium arsenite/doxorubicin (DOX) lipid nanoparticles were constructed via hydrothermal method and thin-film dispersion method for reversing tumor drug resistance. The results showed that the lipid nanoparticles were uniform in size and well dispersed with a mean particle size of (261 ± 7) nm, zeta potential of (-9.6 ± 1.3) mV. The DOX loading efficiency and encapsulation efficiency were 22.6% and 84.0%. The in vitro drug release profile was pH-dependent; the drug accumulation at mitochondria was significantly increased, which then caused overload of calcium and inhibition of P-gp and ATP, thereby reversing tumor drug resistance. The simultaneously released arsenite ion and DOX could synergistically kill the tumor cells. In summary, the lipid nanoparticles prepared in this study have uniform particle size, high drug loading efficiency and encapsulation efficiency, excellent colloidal stability, pH responsiveness, and impressive ability to reverse tumor drug resistance, which may hold great potential in further clinical applications.

Objective: Many studies have shown that respiratory syncytial virus persistent infection may be the main cause of chronic respiratory pathology. However, the mechanism is unclear. Cystic fibrosis transmembrane conduction regulator (CFTR) is an apical membrane chloride channel, which is very important for the regulation of epithelial fluid, chloride ion, and bicarbonate transport. CFTR dysfunction will lead to changes in bronchial secretions and impair mucus clearance, which is related to airway inflammation. In our previous study, we observed the down-regulation of CFTR in airway epithelial cells in respiratory syncytial virus (RSV) infected mouse model. In this study, we further investigated the expression and function of CFTR by constructing an airway epithelial cell model of RSV persistent infection. Methods: 16HBE14o- cells were infected with RSV at 0.01 multiplicity of infection (MOI). The expression of CFTR was detected by real-time RT-PCR, immunofluorescence, and Western blotting. The intracellular chloride concentration was measured by N-(ethoxycarbonylmethyl)-6-methoxyquinolium bromide (MQAE) and the chloride current was measured by whole-cell patch clamp recording. Results:16HBE14o-cells infected with RSV were survived to successive passages of the third generation (G3), while the expression and function of CFTR was progressively decreased upon RSV infection from the first generation (G1) to G3. Exposure of 16HBE14o-cells to RSV led to the gradual increase of TGF-β1 as well as phosphorylation of Smad2 following progressive RSV infection. Disruption of TGF-β1 signaling by SB431542 prevented Smad2 phosphorylation and rescued the expression of CFTR. Conclusion:RSV infection can lead to defective CFTR function in airway epithelial cells, which may be mediated via activation of TGF-β1 signaling pathway.

Objective: To explore the correlation between depression severity and neurocognitive function in patients with late-onset depression . Methods: The patients with late-onset depression treated in Jinhua Second hospital from February 2015 to December 2017 were assigned into the mild,moderate and severe groups according to the severity of depression assessed by the Hamilton Depression Scale-17（HAMD-17）. At the same time,some healthy persons were selected as the control group. Wisconsin Card Sorting Test（WCST）,Verbal Fluency Test（VFT）and Stroop Test were carried out,and the scores of these tests were compared in the four groups. The correlations of WCST, VFT, Stroop Test and HAMD-17 scores were analyzed . Results: There were 32,28,35 and 35 subjects involved in the mild,moderate,severe and control group,respectively. The subjects of the mild group,moderate group and severe group had more total errors,perseverative responses and perseverative errors than the control group,and less percent conceptual level responses than the control group （all P<0.05）. The total errors,perseverative responses,perseverative errors and percent perseverative errors increased and the percent conceptual level responses decreased gradually with the severity of depression（all P<0.05）. The correct numbers of Stroop-consistent group and VFT in the severe group were less than those in the control,mild and moderate group（all P<0.05）,which was significantly different between the mild,moderate and control group （P>0.05）. The HAMD-17 scores were negatively correlated with the correct numbers of Stroop congruent group（r=-0.448,P<0.001）and VFT（r=-0.401,P<0.001）,and were positively correlated with perseverative responses in the WCST（r=0.784,P<0.001） . Conclusion The neurocognitive impairment in patients with late-onset depression aggravated with the severity of depression.

Objective To assess the value of 18F-fluorodeoxyglucose (FDG) PET/CT in the staging,interim therapeutic and prognostic evaluation of mucosa-associated lymphoid tissue (MALT) lymphoma.Methods Thirty-six MALT lymphoma patients (20 males,16 females;average age:61.7 years) confirmed by pathology from January 2008 to January 2018 were retrospectively analyzed.18F-FDG PET/CT were performed before chemotherapy and radiotherapy for staging.The detective sensitivity was evaluated.The staging results of gastric MALT lymphoma and extragastric MALT lymphoma by PET/CT were compared with Fisher exact probability method.PET/CT was performed in 17 of 36 patients after 4 courses of chemotherapy,and 17 patients were divided into positive group (≥≥4) and negative group (＜4) according to scores of Deauville 5-point scale.The progression-free survival (PFS) was evaluated using Kaplan-Meier survival analysis.Results FDG-positive lesions were found in 31 of 36 patients with the sensitivity of 86.1％ (31/36).The results of PET/CT were negative in stage Ⅰ patients.In stage]Ⅱ-Ⅳ patients,the results of 18F-FDG PET/CT combined with bone marrow biopsy were in accordance with the results of clinical staging.The accuracy of PET/CT in staging of gastric MALT lymphoma patients was 9/17,which was significantly lower than that of extragastric MALT lymphoma patients (17/19;P=0.025).The PFS of negative group evaluated by interim PET/CT was longer than that of positive group (x2 =4.16,P＜0.05).The 2-year PFS rates of the 2 groups were (85.7± 13.2)％ and (27.8 ±21.3)％,respectively.The PFS of patients with low expression of Ki-67 was significantly longer than that of patients with high Ki-67 expression (x2=4.22,P＜0.05).Conclusions In stage]Ⅱ-Ⅳ MALT patients,18F-FDG PET/CT combined with bone marrow biopsy can improve the staging accuracy.The staging accuracy of PET/CT in extragastric MALT lymphoma is significantly higher than that of gastric MALT lymphoma.PET/CT and Ki-67 can provide effective information on the prognostic evaluation for patients with MALT lymphoma.