[ ABSTRACT] AIM:To investigate the effect of microRNA-375 ( miR-375) on the viability, cell cycle and apop-tosis of HCT116 cells.METHODS: The expression of miR-375 in different colorectal cancer cell lines was detected by real-time PCR.The miR-375 mimics was transfected into HCT116 cells by LipofectamineTM 2000.The mRNA expression of miR-375 and AEG-1 was detected by real-time PCR.The HCT116 cell viability was detected by MTT assay.The changes of apoptosis and cell cycle distribution were analyzed by flow cytometry.RESULTS:Real-time PCR showed that miR-375 expression was the lowest in HCT116 among 4 colorectal cancer cell lines.The expression level of miR-375 significantly in-creased in miR-375 mimics group compared with that in the negative control group.The high expression level of miR-375 significantly inhibited the mRNA expression of AEG-1.After transfection with miR-375 mimics, the cell viability was in-hibited, the apoptotic rate was increased, the proportion of G1-stage cells was increased, and the proportion of S-stage cells was decreased.CONCLUSION:miR-375 inhibits the viability, mediates the cell cycle arrest and promotes the apoptosis of colon cancer HCT116 cells.miR-375 may act as a tumor suppressor in colorectal cancer by inhibiting AEG-1.

Objective To explore the diagnostic value of impulse oscillometry(IOS) in the patients with COPD. Methods The IOS parameters of 142 cases of COPD (COPD group) were measured and compared with those of 160 normal eases (control group). Linear correlation analysis was done between the IOS parameters and the conventional pulmonary function indexes such as FEV1 / Pred and FEV1/FVC, and the diagnostic value of the IOS parameters in COPD was discussed. Results Compared with those of the control group, respiratory impedance (Zrs),resistance at 5 Hz and 20 Hz (R5,R<<20>) and their difference (R5-R20), central resistance (Re) and peripheral resistance (Rp), resonance frequency (Fres)in the COPD group increased significantly, while reactance at 5 Hz (X5) decreased obviously (P< 0.01 ). In the COPD group, Zrs, Fres, R5, R20, R5-R20 and Rp were all correlated negatively with FEV1 / Pred, but X5 was correlated positively with FEV1/Pred. And the most strong correlation was found between Fres and FEV1/Pred. Fres, R5, R5-R20, Rp were correlated negatively with FEV1/FVC( P all < 0.05). Conclusions IOS is suitable for the diagnosis of COPD,and can be used to evaluate the severity of COPD. The application perspective is very extensive.

The study aimed to establish a population pharmacokinetic/pharmacodynamic (PPK/PD) model of warfarin. PCR-RFLP technique was used to genotype the CYP2C9 and VKORC1 polymorphisms of 73 patients. RP-HPLC-UV method was used to determine the 190 plasma concentrations of warfarin. Application of NONMEM, the clinical information and 263 international normalized ratio (INR) monitoring data were used to investigate the effect of genetic, physiological, pathological factors, other medication on clearance and anticoagulant response. The final model of warfarin PPK/PD was described as follows: CL = θCL · (WT/60)θWT · θCYP · eηCL (if CYP2C9*1/*1, θCYP = 1; if *1/*3, θCYP = 0.708); EC50 = θEC50 · θVKOR · eηEC50 (if VKORC1- 1639AA, θVKOR = 1; if GA, θVKOR = 2.01; V = θV; K(E0) = θK(E0); Emax = θEmax; E0 = θE0 · eηE0. Among them, the body weight (WT), CYP2C9 and VKORC1 genotype had conspicuous effect on warfarin PK/PD parameters. The goodness diagnosis, Bootstrap, NPDE verification showed that the final model was stable, effective and predictable. It may provide a reference for opitimizing the dose regimen of warfarin.

In order to find microRNA associated with HBV infection and to explore the mechanism of the infection, first of all, we found in our preliminary study that in HepG2 cells transfected with HBV expression plasmid, miR-122 expression was up-regulated, suggesting that miR-122 was related to the HBV infection. On this basis, in the present study, miR-122 and pCH9-HBV1.1 plasmid were cotransfected into HepG2 cells. Southern blot detection result showed that miR-122 can inhibit HBV replication. Using MiRanda computer software, HBx was predicted to be the target sequence of miR-122; Luciferase reporter gene system and Western blot detection of HBx protein expression changes were further used to verify the HBx expression regulated by miR-122. And finally, it can be speculated that miR-122 may affected HBV replication by regulating the expression of HBx.
Gene Expression Regulation, Viral ; drug effects ; Hep G2 Cells ; Hepatitis B virus ; drug effects ; genetics ; physiology ; Humans ; MicroRNAs ; genetics ; Trans-Activators ; genetics ; metabolism ; Transfection ; Virus Replication

Aim To study the biotransformation of gly-cyrrhizin in rat intestine-liver. Methods The in situ vascularly perfused rat intestine-liver model was estab-lished with a validated LC-MS/MS method for assay of the model perfusate glycyrrhizin and glycyrrhetinic acid. Results The steady state intestinal and liver ex-traction ratios in the once-through perfused rat intes-tine-liver model for glycyrrhizin were ( 4. 2 ± 0. 6 )%and (28. 0 ± 3. 0)%, respectively; the first-order ab-sorption rate constant for glycyrrhizin in the recircula-tion of perfusate to the intestine model was ( 0. 33 ± 0. 06 ) min-1;after intraduodenal administration of gly-cyrrhizin,the main active metabolite in was the perfu-sate glycyrrhetinic acid, which was also found in intes-tinal luminal fluids. Conclusions The first-pass effi-cacy of glycyrrhizin is obvious and there is only a small amount of metabolite in the intestinal mucosa cells;gly-cyrrhizin is metabolized by gut bacteria or liver cells af-ter oral administration;the in situ vascularly perfused rat intestine-liver model can be used in glycyrrhizin pharmacokinetic studies.

Objective To explore the relationship between tongue conditions and hemorrheology in acute stage of cerebral hemorrhage and to increase the accuracy of tongue conditions for the syndrome differentiation of acute stage of cerebral hemorrhage.Methods Eighty-eight qualified patients were enrolled into this study.The tongue conditions(tongue color,tongue coating and tongue shape) and hemorrheological indexes(whole blood viscosity,whole blood reduced viscosity,plasma viscosity,hematocrit and fibrinogen) were examined,and their relationship was also analyzed.Results The changes of tongue shape was obvious and low-shear whole blood viscosity was increased in the swollen tongue group(P

Background/Aims: To investigate the autoantibody against fumarate hydratase (FH), which is a specific liver failure-associated antigen (LFAA) and determine whether it can be used as a biomarker to evaluate the prognosis of acute-on-chronic liver failure (ACLF). Methods: An immunoproteomic approach was applied to screen specific LFAAs related to differential prognosis of ACLF (n=60). Enzyme-linked immunosorbent assay (ELISA) technology was employed for the validation of the frequency and titer of autoantibodies against FH in ACLF patients with different prognoses (n=82). Moreover, we clarified the expression of autoantibodies against FH in patients with chronic hepatitis B (n=60) and hepatitis B virus-related liver cirrhosis (n=60). The dynamic changes in the titers of autoantibodies against FH were analyzed by sample collection at multiple time points during the clinical course of eight ACLF patients with different prognoses. Results: Ultimately, 15 LFAAs were screened and identified by the immunoproteomic approach.Based on ELISA-based verification, anti-FH/Fumarate hydratase protein autoantibody was chosen to verify its expression in ACLF patients. ACLF patients had a much higher anti-FH autoantibody frequency (76.8%) than patients with liver cirrhosis (10%, p=0.000), patients with chronic hepatitis B (6.7%, p=0.022), and normal humans (0%, p=0.000). More importantly, the frequency and titer of anti-FH protein autoantibodies in the serum of ACLF patients with a good prognosis were much higher than that of patients with a poor prognosis (83.9% vs 61.5%, p=0.019; 1.41±0.85 vs 0.94±0.56, p=0.017, respectively). The titer of anti-FH autoantibodies showed dynamic changes in the clinical course of ACLF. Conclusions The anti-FH autoantibody in serum may be a potential biomarker for predicting the prognosis of ACLF.

The 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-GU) reported several advancements in the field of urothelial carcinoma. Multiple new treatment options for non-muscle invasive bladder cancer (NMIBC) were introduced, providing more choices for bladder preservation in BCG-resistant/failed NMIBC cases. In muscle invasive bladder cancer (MIBC) perioperative treatment, the updated 3-year follow-up data from the CheckMate 274 study demonstrated a clear advantage in disease-free survival for the nivolumab monotherapy adjuvant treatment group. For metastatic urothelial carcinoma (mUC), the final overall survival (OS) report from the IMvigor130 study was published, prompting further considerations for future first-line treatment options in mUC. Additionally, the conference highlighted research progress in upper tract urothelial carcinoma (UTUC).

Objective Toinvestigatethevalueof3.0T MRreducedfield-of-view (rFOV)IVIM-DWIondistinguishingprostate cancerandprostatehypertrophy.Methods 30patientswithpathologicallyprovenprostatecancerand38patientswithprostatehypertrophy accordingtotheresultsofbiopsywereanalyzedretrospectively,whounderwent3.0T MRrFOV multipleb-valueDWIscanpreoperatively.The DWIscanwasperformedusing11b-valuesof0,30,50,100,150,200,400,800,1000,1500and2000s/mm2.ADC,slowdiffusion coefficient(D),fastdiffusioncoefficient(D?)andperfusionfraction(f)weremeasuredoncancerousfociandprostatehyperplasiafoci.Allofthe datawereanalyzed.Results TheADC,D,D?andfvaluesoftheprostatecancerwere(0.61±0.12)×10-3 mm2/s,(0.41±0.08)×10-3 mm2/s, (88.0±40.3)×10-3mm2/s,289.3%±29.4%,respectively,and(09.0±01.7)×10-3mm2/s,(05.4±01.3)×10-3mm2/s,(46.1±15.3)×10-3 mm2/s, 474.3%±10.85%,respectively,forprostatehypertrophy.Thedifferencesamongthefourparameterswerestatisticallysignificant(P<0.05).The areasofADC,D,D?andfvaluesunderROCcurvestodistinguishbetweenprostatecancerandprostatehypertrophywere09.32,08.27,01.58,0.976, respectively.Conclusion 3.0T MRrFOVIVIM-DWIcanreflectthetruewaterdiffusion motionandperfusionintheprostate,and maycontributetothedifferentialdiagnosisofprostatecancerandbenignprostatehyperplasia.

Objective:To explore a fast method to identify and confirm suspected clonorchis sinensis infection.Methods:For suspected clonorchis sinensis infection, the clonorchiasis serum antibody was detected first with ELISA. If the antibody was positive, the fecal examination for eggs was performed. If the fecal examination was negative, duodenal drainage under gastroscopy was recommended to detect eggs from the drainage fluid.Results:A total of 126 patients met the requirements and aged 54.14±13.33 (24- 87). There were 83 cases (65.87%, 83/126) with eggs positive in the drainage fluid, of which 53 cases were male, aged 55.91±11.47 (30-86), and 30 cases female, aged 55.87± 13.85(30-87). There was no significant difference in age between males and females( P>0.05). The time of catheterization (T1) of 126 cases was 3.79 ±1.45 min. The time of drainage (T2) of 126 cases was 31.39 ±14.29 min. There was no significant difference in T1 or T2 between the positive group and the negative group( P>0.05). The detection rates of eggs were 91.57% (76 cases) in intrahepatic bile duct drainage, 81.93% (68 cases) in the bile-cyst juice and 75.90% (63 cases) in the common bile duct fluid. No serious adverse reactions occurred during or after the operation. Conclusion:The detection rate of clonorchiosis sinensis can be effectively improved by the combination of clonorchiasis serum antibody test and gastroscopy-guided duodenal drainage.