Exploration on ALT threshold for initiating antiviral therapy in chronic HBV-infected patients based on results of 707 liver puncture cases / 中国热带医学

@#Abstract: Objective To explore the threshold of ALT for initiating antiviral therapy in HBV infected patients, and to provide a basis for initiating antiviral therapy in chronic HBV-infected patients. Methods This retrospective cohort study recruited 707 consecutive treatment-naïve chronic hepatitis B (CHB) patients undergoing diagnostic liver biopsy in the department of infectious diseases of the Affiliated Hospital of Yan′an University from October 2013 to August 2018. Liver biopsy specimens were obtained under ultrasound guidance using Menghini 16G disposable needles. The METAVIR scoring system, which is commonly used internationally, was used to divide the patients into the group with mild liver tissue injury and the group with significant liver tissue injury, and the alanine aminotransferase (ALT) levels were measured separately. Receiver operating characteristic (ROC) curve and Mann-Whitney U test were used to evaluate the diagnostic value of ALT for significant liver tissue injury under different demographic characteristics. Results Of 707 patients, 292 (41.30%) had significant liver tissue injury confirmed by liver biopsy (METAVIR ≥A2 and/or F2). When the ULN of ALT was set to NICE criteria (30 U/L for males, 19 U/L for females), AASLD criteria (35 U/L for males, 25 U/L for females) and EASL or APASL criteria (40 U/L for males and females), CHB patients with <ULN accounted for 32.38%, 35.03% and 36.07% of significant liver tissue injury, respectively. And significant liver tissue injury in CHB patients with 1-2×ULN accounted for 41.99%, 41.85% and 50.30%, respectively. The optimal ALT critical values were 33 U/L for overall patients, 25 U/L for females, 45 U/L for males, 45 U/L for ≤30 years olds, 33 U/L for>30 years olds, 22 U/L for HBeAg negative and 31 U/L for HBeAg positive patients. Conclusions The threshold of ALT for initiating antiviral therapy in chronic HBV patients should be individualized, especially should be down-regulated for the females, olders and HBeAg-negative patients.

Efficacy of 20G or 25G three-channel vitrectomy for idiopathic macular epiretinal membrane / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To explore the curative effect of 20G and 25G three-channel pars plana vitrectomy in the treatment of idiopathic macular epiretinal membrane,and to provide a theoretical basis for the minimally invasive treatment of idiopathic macular epiretinal membrane.METHODS:Medical records were retrospectively analyzed to explore curative effect.From January 2014 to December 2016,60 patients (60 eyes) with idiopathic macular pucker in our hospital for eye treatment were selected.They were grouped according to different operation way,in 28 patients (28 eyes) using three-channel 20G pars plana vitrectomy as the control group,32 patients (32 eyes) with 25G no-suture conjunctival vitrectomy as observation group.Two groups of patients were evaluated at 3mo after treatment for visual acuity,OCT examination,comfort,and we recorded the operation time,complications and recurrence.RESULTS:The operating time of observation group was 18-25min,average 20±2.15min,the control group was 22-35min,28 ± 2.07min on average,the difference was statistically significant (P＜0.05).At the time of the last follow-up,visual acuity of two groups improved compared with preoperative,without vision decrease.In observation group vision improved in 69％,significantly higher than that of control group (50％),difference was statistically significant (x2 =7.287,P＜ 0.05).Preoperative intraocular pressure of two groups was not significantly different.intraocular pressure of two group at postoperative 1d reduced compared with preoperative (Ftime =31.34,P＜0.01;Fgr.up =17.43,P＜0.01).There was no statistically significant difference at 7d and 1mo compared with preoperative (P＞0.05).Preoperative OCT on macular thickness of the two groups had no statistically significant difference.At 7d,1 and 3mo after treatment,epiretinal membranes disappeared in all patients,and the macular thickness reduced,the macular edema relieved (P＜ 0.05).At postoperative 3mo,two groups of patients were found no recurrence of epiretinal membranes.At 7d,1 and 3mo after treatment,differences between the two groups on macular thickness had no statistical significance.At postoperative 1d,in the control group there were foreign body sensation,swelling,and tears,pain and discomfort,20 patients with eye conjunctival congestion,edema,conjunctival suture to cause discomfort,the symptoms relieved after treatment.In observation group,12 patients with mild conjunctival congestion and edema,dotted hemorrhage at the wound in 4 eyes,5 eyes appeared lower intraocular pressure (6-8mmHg).without special treatment,Postoperative bleeding and edema stopped at 7d,intraocular pressure returned to normal.Patients of observation group did not have foreign body sensation,swelling and discomfort symptoms.At the time of the last follow-up,in the two groups,no iatrogenic retinal detachment,cataract,endophthalmitis and other serious complications occurred.CONCLUSION:The 20G of three-channel pars plana vitrectomy and 25G the no-suture conjunctival vitrectomy are equal for idiopathic macular epiretinal membrane,25G vitrectomy operation time is short with better patient comfort.

Synthesis and preliminary evaluation of anti-HIV agent AZT prodrug / 药学学报

In this research, phosphate and thiophosphate prodrugs 3a, 3b of anti-HIV agent AZT were synthesized, and their anti-HIV activities and cytotoxicities were investigated in vitro. Results showed that the prodrugs 3a and 3b with an IC50 value of 11.0 and 4.0 micromol x L(-1), respectively, were less toxic than AZT (1.0 micromol x L(-1)). Although the EC50 values of both 3a (0.04 micromol x (L(-1) and 3b (0.16 micromol x L(-1)) were lower than that of AZT (0.01 micromol x L(-1)), the therapeutic index (IC50/EC50) of prodrug 3a (275) was much higher than that of both AZT (100) and prodrug 3b (25). This indicated that the prodrug 3a merited further investigation as an anti-HIV agent.

Endocannabinoids Anandamide and Its Cannabinoid Receptors in Liver Fibrosis after Murine Schistosomiasis / 华中科技大学学报（医学）（英德文版）

This study examined endogenous cannabinoid (ECB)-anandamide (AEA) and its can-nabinoid receptors (CBR) in mice liver with the development of schistosomajaponicum.Mice were infected with schistosoma by means of pasting the cercaria onto their abdomens.Liver fibrosis was pathologically confirmed nine weeks after the infection.High performance liquid chromatography (HPLC) was employed to determine the concentration of AEA in the plasma of mice.Immunofluorescence was used to detect the expression of CBR 1 and CBR2 in liver tissue.Morphological examination showed typical pathological changes,with worm tubercles of schistosoma deposited in the liver tissue,fibrosis around the worm tubercles and infiltration or soakage ofinfiammatory cells.Also,CBRI and CBR2 were present in hepatocytes and hepatic sinusoids of the two groups,but they were obviously enhanced in the schistosoma-infected mice.However,the average optical density of CBR1 in the negative control and fibrosis group was 13.28±7.32 and 30.55±7.78,and CBR2 were 28.13±6.42 and 52.29±4.24 (P<0.05).The levels of AEA in the fibrosis group were significantly increased as compared with those of the control group.The concentrations of AEA were (0.37±0.07) and (5.67±1.34) ng/mL (P<0.05).It is concluded that the expression of endocannabinoids AEA and its cannabinoid receptor CBR were significantly increased in schistosoma-infected mice.Endogenous endocannabinoids may be involved in the development of schistosoma-induced liver fibrosis.

Extraction and two-dimensional liquid chromatographic fractionation of plasma membrane proteome of mouse liver cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To extract the plasma membrane proteins from mouse liver cells and investigate the approach for fractionating the protein mixtures by two-dimensional liquid chromatography.</p><p><b>METHODS</b>The plasma membrane of the liver cells from 10 mice was extracted by differential centrifugation and sucrose density-gradient centrifugation. The plasma membrane proteins were exchanged with the start buffer and separated by chromatofocusing in the first-dimensional fractionation. The final results were transformed into UV/pI maps using ProteoVue software.</p><p><b>RESULTS</b>We successfully extracted the plasma membrane proteins from mouse liver cells. Sixteen fractions between pH 8.5-4.0 were recovered in the first-dimensional chromatofocusing followed by 2D- chromatographic fractionation, and the results were displayed as UV/pI maps.</p><p><b>CONCLUSION</b>This approach for fractionating the mouse liver cell plasma membrane protein study provides the foundation for further studies on the functions of plasma membrane proteins and differential proteome of diseases.</p>

Role of ventricular M3 receptor in arrhythmia resulted from cerebral-cardiac syndrome / 药学学报

To detect the function and expression of ventricular M3 receptor (M3R) in cerebral-cardiac syndrome (CCS) model rats and to explore the relationship between the expression of M3R and the arrhythmia resulted from CCS, CCS model rats were induced by occluding right middle cerebral artery. ECG was monitored. Intracellular calcium ([Ca2+]i) changes after agitating M3R were recorded by laser scanning confocal microscope. Changes of M3R expression in the ventricular tissue were detected by Western blotting. QRS and QT intervals in CCS group were remarkably longer than that in sham group. According to the results of Western blotting, the level of M3R expression was remarkably lower in CCS group compared with that in the normal group. KCl induced [Ca2+]i increasing in CCS group could be depressed by choline and the effect of choline could be blocked by 4-DAMP. The lower expression of M3R in CCS group may be one of important reasons of arrhythmia resulted from CCS. M3R that depressed the [Ca2+]i increasing agitated by choline may become a new target to cure arrhythmia resulted from CCS.

8-(N,N-diethylamino)-n-octyl-3,4,5-trimethoxybenzoate inhibited the reduction of cerebral blood flow evoked by 5-HT and KCl in rats / 药学学报

<p><b>AIM</b>To investigate the impact of 8-(N,N-diethylamino)-n-octyl-3,4,5-trimethoxybenzoate (TMB-8) on the change of cerebral blood flow(CBF) induced by 5-HT or KCl in rats.</p><p><b>METHODS</b>The CBF in rats was measured by a Laser-Doppler flowmeter. The cranial window field was superfused with artificial cerebral spinal fluid containing TMB-8, 5-HT or KCl.</p><p><b>RESULTS</b>12.5, 25 and 50 mumol.L-1 TMB-8 showed no significant effect on rest CBF in rats. 12.5, 25 and 50 mumol.L-1 TMB-8 apparently inhibited the decline of CBF evoked by 1 or 2 mumol.L-1 5-HT. When persistent reduction of CBF were evoked by 1 mumol.L-1 5-HT, TMB-8 markedly increased the CBF in a concentration-dependent manner. The reduction of CBF induced by 20 or 40 mmol.L-1 KCl was also suppressed by 12.5, 25 and 50 mumol.L-1 TMB-8. While persistent reduction of CBF was evoked by 20 mmol.L-1 KCl. TMB-8 markedly increased the CBF in a concentration-dependent manner.</p><p><b>CONCLUSION</b>These results indicate that TMB-8 is effective in preventing and treating the reduction of CBF induced by 5-HT or KCl, and improved the supply of blood in rat brain during ischemia.</p>