Efficacy and safety of tenofovir alafenamide fumarate in treatment of chronic hepatitis B patients aged ≥60 years in Qingdao, China / 临床肝胆病杂志

Objective To investigate the application value of tenofovir alafenamide fumarate (TAF) in elderly patients with chronic hepatitis B (CHB) and its influence on bones and kidneys. Methods A total of 36 CHB patients, aged ≥60 years, who received TAF antiviral therapy in Qingdao Municipal Hospital, The Affiliated Hospital of Qingdao University, Qingdao Sixth People's Hospital, Chengyang People's Hospital, and Jimo People's Hospital from June 2021 to October 2022 were enrolled in this study, and all patients received TAF (25 mg/d) antiviral therapy. Related data were collected at baseline and weeks 24 and 48 of treatment, including virological indicators, biochemical parameters, urinary protein electrophoresis indices, transient elastography (FibroScan), and bone mineral density. Virological indicators included high-sensitivity HBV DNA quantification; biochemical parameters included total bilirubin, direct bilirubin (DBil), indirect bilirubin (IBil), alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, total bile acid (TBA), glucose, blood urea nitrogen, creatinine, estimated glomerular filtration rate, and cystatin C (Cys C); urinary protein electrophoresis indices included urinary β2 microglobulin (β2-MG), urinary retinol (URBP), and urinary α1 microspherin (α1-MG). The paired t -test was used for comparison of normally distributed continuous data before and after treatment, and the Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment; the chi-square test or the Fisher's exact test was used for comparison of categorical data. Results A total of 36 CHB patients completed 24 weeks of follow-up. The complete virological response rate after 24 weeks of treatment was higher than that at baseline [83.3% (30/36) vs 77.8% (28/36), χ 2 =0.36, P =0.55], and there were significant reductions in DBil ( t =-2.42, P =0.02) and Cys C ( t =-4.34, P 0.05). Conclusion TAF has a good antiviral effect in CHB patients aged ≥60 years and can help more CHB patients achieve complete virological response, without causing damage to the kidney, and it can also improve bone mineral density and liver fibrosis degree.

Research advances in tenofovir alafenamide fumarate in treatment of special chronic hepatitis B / 临床肝胆病杂志

There are a large number of individuals with HBV infection in China, which seriously endangers public health safety. As a first-line drug used in clinical practice, tenofovir alafenamide fumarate (TAF) has the characteristics of strong efficacy, low drug resistance, and bone and kidney safety. This article summarizes the role of TAF in patients with special types of chronic hepatitis B, such as low-level viremia, multidrug resistance, pregnancy, liver failure, and liver transplantation, and the analysis shows that TAF can reduce viral load in patients with low-level viremia to achieve virologic response, provide new regimens for patients with drug resistance, block mother-to-child transmission, reduce the mortality rate of patients with end-stage liver disease, and improve renal function in patients with chronic kidney disease.

Rhizomelic chondrodysplasia punctata type Ⅰ in a fetus due to novel pathogenic mutation in PEX7 gene / 中华围产医学杂志

We report a case of a fetus with rhizomelic chondrodysplasia punctata type Ⅰ. Ultrasound examination of the pregnant women at 23 weeks of gestation showed multiple fractures in bilateral femurs, thick metaphysis, severely short, thickened and curved bilateral humerus with multiple fracture images, some of which were callu formation after fracture. The pregnancy was terminated at 23 +2 gestational weeks, samples of fetal skin tissue were taken after birth, and parental peripheral blood was collected for whole exome sequencing, which revealed a frameshift mutation c.179delT (p.F61Lfs*13) in the PEX7 gene of chromosome 6, and the heterozygous deletion (141 kb) occurred in the region of chromosome 6 137105182-137245871, covering the pathogenic gene PEX7. The analysis of parental samples suggested that the mutations were compound heterozygous mutations, none of which had been previously reported and were determined to be pathogenic mutations. The severe clinical phenotype of this case may be caused by severe damage of PEX7 gene contributed by the frameshift mutation and large fragment deletion mutations.

Effects of Ligustri lucidi Fructus Extract on the Differentiation of Osteoclasts and the Proliferation of Osteoblasts / 中国药房

OBJECTIVE： To investigate the effects of Ligustri lucidi Fructus extract on the differentiation of osteoclasts and the proliferation of osteoblasts. METHODS： Rabbit primary bone marrow cells were induced with 1a，25-Dihydroxyvitamin D3 to obtain osteoclasts. After treated with low-dose， medium-dose and high-dose of L. lucidi Fructus ethanol and water extract （both 2， 20， 200 mg/L）， TRACP activity determined method was used to detect the activity of TRACP in cell lysis solution and the number of TRACP positive cells. The number of celluar bone resorption lacunae and the percentage of bone lacunae area were detected by toluidine blue staining. Osteoblasts were obtained by L-ascorbic acid， β-sodium glycerophosphate and dexamethasone-induced subcloning 14 of cranial parietal anterior osteocytes in mice. MTT assay and APK activity assay were used to detect relative proliferation rate of cells and the activity of APK. RESULTS： After treated with different doses of L. lucidi Fructus extract， the number of TRACP positive cells， the number of bone resorption lacunae and their area were changed in varying degrees. TRACP activity， the number of its positive cells， the number of bone resorption lacunae and the percentage of bone lacunae area in different dosage groups of L. lucidi Fructus ethanol extract and high-dose of water extract； the TRACP activity， the number of its positive cells and the percentage of bone lacunae area in L. lucidi Fructus water extract medium-dose group were decreased significantly， while the number of bone resorption lacunae in L. lucidi Fructus water extract low-dose group was increased significantly （P＜0.05 or P＜0.01）. The relative proliferation rate of cells in L. lucidi Fructus extract low-dose and medium-dose groups and APK activity of cells in extract groups were significantly increased， while the relative proliferation rate of cells were decreased significantly in L. lucidi Fructus ethanol extract and water extract high-dose groups （P＜0.01）. CONCLUSIONS： L. lucidi Fructus extract can inhibit TRACP activity of osteoclasts， change the bone resorption function of osteoclasts and the proliferation behavior of osteoblasts and increase APK activity of osteoclasts.

Distribution of algesia sensitized acupoints in the patients of intestinal cancer / 中国针灸

<p><b>OBJECTIVE</b>To judge whether algesia sensitization of some acupoints is existed and whether the acupoint algesia sensitization area is expanded in the patients of intestinal cancer.</p><p><b>METHODS</b>Totally, 30 patients of intestinal cancer and 30 healthy subjects were included. The electronic Von Fray was used to determine the pressure-pain thresholds at 13 acupoints relevant with gastrointestinal disorders and the reference points at the sites 1and 2lateral to those points as well as the sites at the corresponding nerve segments. Compared with the pressure-pain thresholds at the reference points of the different segments, the relative value was calculated. The changes were analyzed in the pressure-pain thresholds at the relevant acupoints on the body surface in the patients of intestinal cancer as compared with the relative pressure-pain thresholds in the healthy volunteers.</p><p><b>RESULTS</b>The pressure-pain thresholds at Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Quchi (LI 11) and Dachangshu (BL 25) in the patients of intestinal cancer were all significantly reduced as compared with those of the healthy subjects (<0.05,<0.01,<0.001). At the non-acupoint sites 1and 2lateral to those acupoints as well as at the sites of the same segments, the pressure-pain thresholds were reduced significantly as compared with the control group (<0.05,<0.01,<0.001). Particularly, the sensitization zone of Yinlingquan (SP 9) focused on the acupoint, the site 1lateral to it as well as the non-acupoint sites of the same segments (<0.01,<0.001).</p><p><b>CONCLUSION</b>The acupoint sensitization is displayed at Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Quchi (LI 11), Dachangshu (BL 25) and Yinlingquan (SP 9) and the sensitization area is expended in the patients of intestinal cancer.</p>

Density and hydrostatic settling velocity of Biomphalaria straminea / 中国血吸虫病防治杂志

Objective To understand the eco-hydraulics characteristics of Biomphalaria straminea,the intermediate host of Schistosoma mansoni. Methods The drainage method and settlement tube method were applied to measure B. straminea's den-sity and hydrostatic settling velocity respectively. Results The density of B. straminea was 1.04-1.16 g/cm3,and the average value was 1.08 g/cm3. The hydrostatic settling velocity was 2.32-12.92 cm/s. Conclusions The eco-hydraulics characteristics of B. straminea is different from Oncomelania hupensis,and more attention should be paid to the hydraulic measures for the con-trol of B. straminea.

Role and mechanism of action of fibroblast growth factor-21 in reducing triglyceride in nonalcoholic fatty liver disease / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the role and mechanism of action of fibroblast growth factor-21 (FGF-21) in reducing triglyceride (TG) in the in vitro and in vivo models of nonalcoholic fatty liver disease (NAFLD).</p><p><b>METHODS</b>(1) A mixture of free fatty acids was used to establish a model of steatosis in L02 cells, and the cells were treated with various concentrations of FGF-21 or fenofibrate. Twenty-four hours later, oil red O staining was performed to observe the degree of steatosis, and intracellular TG content was determined. RT-PCR and Western blot were applied to measure the mRNA and protein expression of sterol regulatory element-binding protein-1c (SREBP-1c). (2) High-fat diet was used to establish a mouse model of steatosis, and these mice were intraperitoneally injected with FGF-21 or fenofibrate. Eight weeks later, whole blood and liver samples were collected, and HE staining was performed to observe steatosis. Meanwhile, the serum levels of TG, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured, and TG content in the liver was also measured. One-way analysis of variance was used for comparison of data between multiple groups, and the least significant difference t-test was used for comparison between any two groups.</p><p><b>RESULTS</b>(1) Compared with the control group, the model group showed significant steatosis, with significant increases in intracellular lipid droplets and TG content (t = -20.57, P < 0.01), while FGF-21 reduced the number of intracellular lipid droplets and TG content (F = 98.16, P < 0.01) in a dose-dependent manner. In addition, the model group had significantly increased mRNA and protein expression of SREBP-1c compared with the control group (t = -10.73 and -0.1006, both P < 0.01), while FGF-21 down-regulated the mRNA and protein expression of SREBP-1c (F = 161.35 and 36.72, both P < 0.01). (2) Compared with the mice in the control group, those in the model group showed significant steatosis and had significant increases in serum TG level and TG content in the liver (t = -18.84 and 15.71, both P < 0.01). FGF-21 relieved hepatic steatosis and reduced the serum TG level and TG content in the liver (t = 18.11 and 9.46, both P < 0.01). Moreover, FGF-21 reduced the serum levels of ALT and AST in NAFLD mice (t = 25.93 and 12.50, both P < 0.01).</p><p><b>CONCLUSION</b>FGF-21 can inhibit the synthesis of TG through suppressing the expression of SREBP-1c, which further confirms the potential therapeutic effect of FGF-21 in the treatment of NAFLD. This may provide new ideas for the treatment of NAFLD.</p>