Objective To study the role of JAK-STAT singal transduction pathway in the interstitial fibrosis of unilateral ureter obstruction (UUO)mice. Methods Mice UUO model was established and the phosphorylation of JAK-STAT was examined at day 1,4,7 and 14 after ligation of the ureter.Mice in the treatment group were treated with daily injection of selective JAK2 inhibitor AG490 starting 2 h before ureter ligation until sacrifice while vehicle alone was given to mice in the model control group.Mice were sacrificed at day 14 after the establishment of model.Renal tubular lesion and interstitial fibrosis were assessed on paraffin section.Immunohistochemistry was used to detect renal macrophage infihration and α-SMA expression.The expression of collagen Ⅲ and MCP-1 mRNA was measured by RT-PCR.Phosphorylation of JAK2and STAT1 was examined by Western blotting. Results JAK2-STAT1 signaling transduction pathway was activated in UUO model.The activation of JAK2-STAT1 was closely correlated with the progression of renal injury,tubular histological lesions and interstitial fibrosis.AG490 treatment significantly inhibited the phosphorylation of JAK2 and STAT1 (P＜0.01).AG490 treatment also significantly reduced tubular lesions[(21.7 ±1.7)% vs (49.4±1.0)%]and interstitial fibrosis(1.0±0.1 vs 2.3±0.2),α-SMA expression(0.9±0.1 vs 2.1±0.2)and maerophage accumulation[(13.3±1.6)cells/HPF vs (34.4±1.0)cells/HPF](all P＜0.01).In addition,AG490 significantly inhibited the expression of collagen Ⅲ and MCP-1 mRNA. Conclusion JAK-STAT signaling plays an important role in renal tubulointerstitial inflammation and fibrosis.

OBJECTIVE: To investigate the effect of gene silencing of Bmi-1 on proliferation regulation of CD44+ nasopharyngeal carcinoma cancer stem-like cells (CSC-LCs). METHOD: The sequence-specific short hairpin RNA lentivirus targeting at human Bmi-1 gene (LV-Bmi-1shRNA) was constructed and was used to infect CD44+ nasopharyngeal carcinoma cells which were sorted by flow cytometry. A lentiviral which included a random sequence was also designed to serve as a negative control. We employed fluorescence microscope and flow cytometry to detect infection efficiency; real-time PCR was used to detect Bmi-1 and its downstream gene while each protein expression level was confirmed by western blotting protocol; CCK-8 proliferation assay was applied to measure proliferation capacity; tumor spheroid assay was used to evaluate the self-renewal capacity. Colony formation assay was used to measure cell colony formation capability; flow cytometry analyzed cell cycle distribution. RESULT: The constructed LV-Bmi-1shRNA successfully infected into the CD44+ nasopharyngeal carcinoma cells. The infection efficiency could reach above 95%; LV-Bmi-lshRNA effectively inhibited Bmi-1 mRNA and protein expression, while the downstream gene p16INK4a and p14ARF mRNA as well as protein expression level were upregulated (P < 0.05). Notablely, the proliferation, colony formation, self-renewal capabilities of the experimental group decreased significantly (P < 0.05). In addition, the cell cycle arrested at the G0-G1 phase. CONCLUSION Gene silencing of Bmi-1 inhibited the proliferation, colony formation and self-renewal capabilities of the CD44+ nasopharyngeal carcinoma CSC-LCs, inhibited the cell cycle processes, which may mediate through Bmi1-p16INK4a/p14ARF-p53 pathway. Our experimental results indicated that Bmi-1 gene may play an important role in the maintenance of the stem cell-like characteristics of CD44+ nasopharyngeal carcinoma cells. Bmi-1 gene may be a potential new target for the treatment of nasopharyng al carcinoma in the future.
Carcinoma ; Cell Cycle ; Cell Division ; Cell Line, Tumor ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; Gene Silencing ; Humans ; Hyaluronan Receptors ; metabolism ; Lentivirus ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; genetics ; pathology ; Neoplastic Stem Cells ; cytology ; Polycomb Repressive Complex 1 ; genetics ; RNA, Messenger ; RNA, Small Interfering ; Tumor Suppressor Protein p14ARF ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

This article reviews the overview of dyadic coping, assessment tools, and the current application status of dyadic coping interventions in patients with gestational diabetes mellitus (GDM) and their spouses, aiming to provide a reference for related research.

Bladder cancer is one of the most common malignant tumors of the urinary system, among which urothelial carcinoma is the main one. The traditional treatment methods are mainly surgical resection and chemotherapy, but the treatment effect of advanced patients is not good, and the prognosis is poor. In recent years, with the development of immune checkpoint inhibitors, there are many treatment options that are more effective than traditional therapies. Programmed cell death protein 1 (PD-1)and programmed cell death ligand 1(PD-L1)inhibitors stop the negative regulation of the immune system by blocking the binding of PD-1 and PD-L1, thereby enhancing the anti-tumor activity of the body's immune system. This article mainly reviews the efficacy and safety of PD-1/PD-L1 inhibitors commonly used in the clinical treatment of locally advanced or metastatic urinary tract carcinoma of the bladder.

Objective To explore the effect of hydromorphone on hemodynamics after general anesthesia in elderly patients with hypertension under evaluation of Bioz noninvasive monitoring system.Methods Sixty elderly hypertension patients with selective abdominal operation under general anesthesia were randomly divided into hydromorphone group (HM group) and normal saline group (SP group),and 15 min before the end of surgery,hydromorphone was injected in the MH group,while the normal saline was injected in the control group.The indicators such as heart rate (HR),mean arterial pressure (MAP),cardiac output (CO),cardiac output index (CI) and systemic vascular resistance (SVR) were measured at different time points of before induction of anesthesia (T1),extubation (T2) and 10 min after extubation (T3).Recovery time of spontaneous breathing,awaking time,extubation time and out of PACU time were recorded.The visual analogue score (VAS),Ramsay sedation score at the PACU were also recorded at 5 min (H1),15 min (H2) and 30 min (H3).Results Compared with HM group,HR,MAP,SVR,VAS and Ramsay score increased significantly in the SP group (P ＜ 0.05).Compared with the indexes at T1,HR,MAP,SVR increased significantly while CO,CI decreased significantly at T2 (P ＜ 0.05).In both groups,SVR at T3 decreased but was significantly higher than that at T1 (P ＜ 0.0 5).compared between two groups at H1 time point in PACU,VAS and Ramsay score in group SP at H2,H3 time point were no different (P ＞ 0.05).VAS and Ramsay scores in HM group at H2,H3 were increased significantly (P ＜0.05).There were no significant differences in the recovery time of spontaneous breathing,awaking time and extubation time between two groups (P ＞ 0.05).Conclusion Bioz non-invasive hemodynamic monitoring system can provide effective hemodynamic information,and subcutaneous injection of 1 mg hydromorphone before the end of operation can effectively maintain the hemodynamic stability during the recovery period of general anesthesia in elderly patients with hypertension.

Objective To explore the effect of hydromorphone on hemodynamics after general anesthesia in elderly patients with hypertension under evaluation of Bioz noninvasive monitoring system.Methods Sixty elderly hypertension patients with selective abdominal operation under general anesthesia were randomly divided into hydromorphone group (HM group) and normal saline group (SP group),and 15 min before the end of surgery,hydromorphone was injected in the MH group,while the normal saline was injected in the control group.The indicators such as heart rate (HR),mean arterial pressure (MAP),cardiac output (CO),cardiac output index (CI) and systemic vascular resistance (SVR) were measured at different time points of before induction of anesthesia (T1),extubation (T2) and 10 min after extubation (T3).Recovery time of spontaneous breathing,awaking time,extubation time and out of PACU time were recorded.The visual analogue score (VAS),Ramsay sedation score at the PACU were also recorded at 5 min (H1),15 min (H2) and 30 min (H3).Results Compared with HM group,HR,MAP,SVR,VAS and Ramsay score increased significantly in the SP group (P ＜ 0.05).Compared with the indexes at T1,HR,MAP,SVR increased significantly while CO,CI decreased significantly at T2 (P ＜ 0.05).In both groups,SVR at T3 decreased but was significantly higher than that at T1 (P ＜ 0.0 5).compared between two groups at H1 time point in PACU,VAS and Ramsay score in group SP at H2,H3 time point were no different (P ＞ 0.05).VAS and Ramsay scores in HM group at H2,H3 were increased significantly (P ＜0.05).There were no significant differences in the recovery time of spontaneous breathing,awaking time and extubation time between two groups (P ＞ 0.05).Conclusion Bioz non-invasive hemodynamic monitoring system can provide effective hemodynamic information,and subcutaneous injection of 1 mg hydromorphone before the end of operation can effectively maintain the hemodynamic stability during the recovery period of general anesthesia in elderly patients with hypertension.

Inflammatory myofibroblastoma is a rare soft tissue tumor that is most common in the lungs and less common in the bladder. Inflammatory myofibroblastoma is a borderline tumor with a probability of malignant transformation, and surgical resection is the preferred treatment. Umbilical duct cysts belong to benign lesions and can be treated conservatively for asymptomatic patients. Surgical resection is preferred for those with concurrent infections. Due to the lack of specificity in clinical and imaging manifestations of cystitis myofibroblastoma, it is prone to misdiagnosis and over treatment. Currently, the diagnosis mainly relies on postoperative pathological results.

OBJECTIVE To explore the anti-respiratory syncytial virus(RSV) pharmacodynamic material basis of Scutellaria Baicalensis. METHODS Network pharmacology method was used to analyze the anti-RSV targets of Scutellaria baicalensis. UPLC-QTOF-MS/MS was used to characterize the consensus components in Scutellaria Baicalensis. A mouse model of RSV pneumonia was established, and the changes of mouse body weight, lung index, lung pathological sections and IL-6 were detected. The gray correlation method was used to analyze the spectrum-effect data of 50 batches of Scutellaria baicalensis samples, and the effective components of Scutellaria baicalensis against RSV pneumonia mice were mined. RESULTS The protein-protein interaction network results determined that the core targets of Scutellaria baicalensis against RSV were AKT1, IL-6, TNF, MAPK3, SRC, HSP90AA1 and PTGS2; overall animal experiment proved that lung index of Scutellaria baicalensis decreased to varying degrees, and the inflammatory factor IL-6 had significant differences; grey correlation analysis showed that the anti-RSV chemical components in Scutellaria baicalensis were mainly flavonoid glycosides.CONCLUSION Using the network pharmacology method to determine the pharmacodynamic target, the gray correlation degree analysis component-target data, the method of mining the pharmacodynamic material basis is feasible, baicalin, wogonin, chrysin-6-C-arabinose-8-C-flavonoid glycoside, chrysin-6-C-arabinose-8-C-arabinoside and chrysin-7-O-glucuronide can be used as Q-Markers of Scutellaria baicalensis for quality evaluation.

OBJECTIVE To establish a method for simultaneous determination of atorvastatin （ATV） and its active metabolites 2-hydroxy atorvastatin acid （2-HAT）， 4-hydroxy atorvastatin acid （4-HAT） and toxic metabolite atorvastatin lactone （ALT） in rat plasma and apply it for pharmacokinetic study. METHODS LC-MS/MS method was adopted for analysis. The one-step precipitation method was used for processing plasma samples （plasma samples were pretreated by acidification to adjust pH value so as to prevent inversion of configuration）， gradient elution was used to analyze the samples， and the analysis time was 5 min. Electrospray positive ionization was adopted， and positive ion scanning was performed in multi-reaction monitoring. The m/z of quantified ion pairs of ATV and its metabolites such as 2-HAT， 4-HAT and ATL， and internal standard pitavastatin were 559.3→ 440.2， 575.2→440.3， 575.0→440.2， 540.9→448.2 and 422.2→290.0， respectively. After conducting a comprehensive methodological investigation of the analytical method， the concentrations of ATV and its metabolites 2-HAT， 4-HAT，and ATL were determined， and the pharmacokinetic parameters of ATV and its metabolites were calculated using the non- compartment model of WinNonlin 6.1. RESULTS The results of methodological validation showed that endogenous substances in blank plasma did not interfere with the determination of the components to be tested， and the standard curve had a good linear relationship； the lower limits of quantification for ATV， 2-HAT， 4-HAT and ATL were 0.5， 0.5， 0.25 and 0.063 nmol/L， respectively. The precision， accuracy， recovery， matrix effect and stability investigation were all in line with the requirements of biological analysis. Pharmacokinetic analysis showed that after intragastric administration in rats， ATV calcium metabolized rapidly， and was mainly exposed to blood circulation in the form of ATV and 2-HAT， with the lowest concentration of lactone-type metabolites. CONCLUSIONS The established method is precise， rapid and accurate for plasma concentration analysis of ATV and its active/toxic metabolites. The application of the method could help to fully elucidate the pharmacokinetic characteristics of atorvastatin calcium in rats.

OBJECTIVE To establish a discriminant analysis of a mathematical model for distinguishing genuine and fake Dalbergiae Odoriferae Lignum based on the digitization of powder color. METHODS The 39 samples of Dalbergiae Odoriferae Lignum sold in the market were collected, and the L*,a*, b*, E*ab values of Dalbergiae Odoriferae Lignum powder were measured by using a color difference meter, and the authenticity of the Dalbergiae Odoriferae Lignum sold in the market was identified by using microscopic and thin layer methods, and a discriminant analysis model for the authenticity of Dalbergiae Odoriferae Lignum was established through statistical analysis. RESULTS A mathematical model for distinguishing true and false color difference of Dalbergiae Odoriferae Lignum was established by measuring the color difference value of Dalbergiae Odoriferae Lignum powder in the market. The results of distinguishing authenticity and falsehood were consistent with those of ordinary discrimination. CONCLUSION The method of rapid identification of true and false Dalbergiae Odoriferae Lignum by color difference value is effective, which can provide reference and basis for color difference identification and analysis of Chinese herbal medicines.