Heme oxygenases (HO) are rate-limiting enzymes which degrade heme into carbon monoxide,biliverdin and free iron. HO-1 is the inducible form of HO. Induction and over-expression of HO-1 or inhibition of HO-1 degradation have been shown to interfere with replication of hepatitis B and C viruses,acute and chronic liver inflammation,and progression to fibrosis. HO-1 as well as its reaction products of heme degradation has been linked to cytoprotection by its anti-inflammatory,antioxidative and anti-apoptotic effects,displayed a broad range of protective effects against hepatic damage,and showed beneficial effects on ischemia-reperfusion injury,acute/chronic graft rejection and graft survival rate in liver transplantation. However,HO-1 has been found to be over-expressed in tumor cells. Inhibition of HO-1 expression can promote tumor cell apoptosis,decrease growth of HCC and reduce angiogenesis, suggesting that HO-1 is a potential target in the treatment of hepatic cancer. To validate the target property of HO-1,this review analyzed the effects and mechanism of action of HO-1 and its products in viral hepatitis,liver injury,hepatic fibrosis,liver transplantation and hepatocellular carcinoma. Given HO-1′s marked anti-viral,anti-inflammatory and hepatoprotective properties,the inhibitory effect of its down-modulation on hepatic cancer and the strategy to target HO-1 may promise new areas in both drug development and clinical therapy of liver diseases.

Objective:To investigate the effects and underlying mechanisms of XRCC3 on esophageal squamous-cell carcinoma (ESCC) radiotherapy response. Methods:Expression levels of XRCC3 were detected by reverse transcription PCR, Western blot, and immunohistochemistry. We knocked down XRCC3 with lentiviral infection in ESCC cells. Cell apoptosis was examined by flow cytom-etry. DNA damage and telomere dysfunction-induced foci were determined by immunofluorescence. Results:The expression levels of XRCC3 in ESCC cells and tissues were higher than those in normal esophageal epithelial cells and corresponding adjacent noncancer-ous esophageal tissues. Knockdown of XRCC3 in ESCC cells substantially increased the therapeutic efficacy of radiation. We demon-strated that the radiation resistance of XRCC3 was attributed to the XRCC3-maintaining telomere stability, which reduced ESCC cell death through radiation-induced apoptosis. Conclusion: Our data suggested that XRCC3 protects ESCC cells from ionizing radia-tion-induced DNA damage and death by enhancing telomere stability. Thus, XRCC3 can be used as a promising therapeutic target for ESCCs.

ObjectiveTo study the CT values of certain phantoms scanned by various CT scanners with dissimilar parameters.Methods The CT values of tissue equivalent inserts was measured in the TM164 and CIRS-062 phantom scanned by TOSHIBA AQUILIONTM,SIEMENS SOMATOMTMSENSATIONTM 64 and SIEMENS SOMATOMTM SENSATIONTM OPEN with different voltages,currents and slice thicknesses and then the corresponding CT-to-density curves was compared. Results There are no significant differences of CT values with various currents and slice thicknesses and also for low atom number materials scanned by different scanners with various tube voltages.The CT values of high atom number materials have obvious differences scanned with tube voltage,the maximum is about 400 HU.There are also significant differences between CT-density curves of two phantoms in the range from soft tissues to dense bone,the maximum is up to 500 HU.ConclusionsCT-density curves were highly affected by materials of phantoms,scanners and tube voltages.It is necessary to measure the curve with a comfortable phantom and certain scanner to assure the accuracy for dose calculation for treatment planning system.

The hope level of stroke patients affects their functional recovery and quality of life. This paper reviews the concept of hope, the measurement tools of hope level, the influencing factors of stroke patients' hope level, the impact of hope on stroke patients, and the intervention measures of hope level, aiming at improving the hope level of stroke patients and providing reference for formulating personalized psychological intervention for patients.

OBJECTIVETo investigate the antioxidant and cytotoxic properties of five diarylheptanoids (1-5) isolated from the rhizomes of Zingiber officinale.

METHODVarious models such as scavenging superoxide anions and 1,1-diphenyl-2- picrylhydrazyl (DPPH) radicals, inhibiting lipid peroxidation, as well as protecting of rat pheochromocytoma (PC12) cells induced by hydrogen peroxide (H2O2) were employed to assay the antioxidative effects of the diarylheptanoids. The cytotoxicities of compounds 1-5 were measured with MTT assays.

RESULTThe test compounds (1-5) showed promising DPPH inhibitory activities, and compound 5 exhibited the strongest DPPH scavenging activity with an IC50 value of (22.6+/-2.4) micromol x L(-1). Compounds 1, 3 and 4 showed potential anti-peroxidative effects with inhibitory rates of (66.3+/-15.4)%, (68.7+/-15.8)% and (72.2+/-10.6)%, respectively, at 100 microg x mL(-1). It could be observed that compounds 1, 3 and 4 demonstrated significant neuroprotective activities in a dose-dependent manner. Moreover, compound 3 exhibited certain cytotoxicities against human chronic myelogenous leukemia cells (K562) and its adriamycin-resistant cells (K562/ADR) with IC50 values of (34.9+/-0.6), (50.6+/-23.5) micromol x L(-1), respectively.

CONCLUSIONIn vitro results demonstrated that five diarylheptanoids (1-5) isolated from the roots of Z. officinale were capable of scavenging radicals, inhibiting lipid peroxidation and protecting PC12 cells against the insult by H2O2. Additionally, compound 3 could inhibit the growth of K562 and K562/ADR cells.

Animals ; Antioxidants ; toxicity ; Cell Proliferation ; drug effects ; Cytotoxins ; toxicity ; Diarylheptanoids ; isolation & purification ; metabolism ; toxicity ; Free Radicals ; metabolism ; Ginger ; chemistry ; Humans ; Hydrogen Peroxide ; metabolism ; K562 Cells ; Oils, Volatile ; pharmacology ; PC12 Cells ; Rats ; Rats, Sprague-Dawley

Objective:To investigate the expression of microRNA (miR) -26a in human skin fibroblasts during photoaging induced by ultraviolet A (UVA) , and to evaluate the effect of up-or down-regulation of miR-26a expression on the methylation level of the whole genome, the target gene enhancer of zeste homolog 2 (EZH2) and cell aging.Methods:Some human skin fibroblasts were irradiated with 10 J/cm 2 UVA once a day for 7 consecutive days, RNA was extracted on days 0, 3 and 7, and real-time quantitative reverse PCR (RT-PCR) was performed to determine the expression of miR-26a; miR-26a mimics and inhibitors were transfected into fibroblasts to up-or down-regulate the expression of miR-26a respectively, and fluorescence microscopy and RT-PCR were performed to determine the expression of miR-26a and evaluate the transfection efficiency. Some human skin fibroblasts were divided into 6 groups: blank control group receiving no treatment, UVA group treated with UVA irradiation according to the above method, miR-26a mimic group transfected with miR-26a-mimics, UVA+miR-26a mimic group transfected with miR-26a-mimics followed by UVA irradiation, miR-26a inhibitor group transfected with miR-26a inhibitors, UVA+miR-26a inhibitor group transfected with miR-26a inhibitors followed by UVA irradiation. On day 7, cells in each group were collected after the end of UVA irradiation. Then, flow cytometry was performed to detect cell cycle, DNA methylation quantitative detection kit was used to detect the methylation level of whole genome, RT-PCR was conducted to determine the mRNA expression of EZH2 (a histone-lysine N-methyltransferase enzyme) , DNA methyltransferase 1 (DNMT1) and miR-26a, and Western blot analysis was performed to determine the protein expression of EZH2 and DNMT1. Statistical analysis was carried out by using one-way analysis of variance and least significant difference- t test. Results:Compared with the unirradiated control group, the expression of miR-26a gradually increased in the UVA irradiation group over time during the culture, and there was a significant difference in the expression of miR-26a between the two groups after 7 days of UVA irradiation ( t=5.295, P < 0.05) . Strong fluorescence signals were observed in the miR-26a mimic-or miR-26a inhibitor-transfected fibroblasts, suggesting a high transfection efficiency. Flow cytometry showed that the proportion of cells at G1 phase significantly differed among the blank control group, UVA group, miR-26a mimic group, UVA+miR-26a mimic group, miR-26a inhibitor group, and UVA+miR-26a inhibitor group (52.82% ± 2.56%, 78.56% ± 4.34%, 53.63% ± 3.13%, 89.52% ± 4.17%, 54.39% ± 3.86%, 65.34% ± 4.78%, respectively; F=46.728, P < 0.01) , and significantly higher in the UVA group than in the blank control group ( t=8.848, P < 0.01) , higher in the UVA+miR-26a mimic group than in the miR-26a mimic group and UVA group ( t=11.922, 3.154, P < 0.01, < 0.05, respectively) , and higher in the UVA+miR-26a inhibitor group than in the miR-26a-inhibitor group ( t=3.087, P < 0.05) , but significantly lower in the UVA+miR-26a inhibitor group than in the UVA group ( t=3.547, P < 0.05) . Detection of the genome-wide methylation level showed that the methylation level ( A450 value) significantly differed among the above groups (0.676 ± 0.024, 0.323 ± 0.043, 0.506 ± 0.035, 0.169 ± 0.024, 0.602 ± 0.036, 0.422 ± 0.029, respectively, F=97.402, P < 0.01) , and significantly lower in the UVA group than in the blank control group ( P < 0.01) , lower in the UVA+miR-26a mimic group than in the miR-26a mimic group and UVA group (both P < 0.01) , and lower in the UVA+miR-26a inhibitor group than in the miR-26a inhibitor group ( P < 0.01) , but significantly higher in the UVA+miR-26a inhibitor group than in the UVA group ( P < 0.05) . RT-PCR and Western blot analysis showed significant differences in the mRNA and protein expression of EZH2 and DNMT1 respectively among the 6 groups (both P < 0.05) , which were significantly lower in the UVA group than in the blank control group ( P < 0.05) , lower in the UVA+miR-26a mimic group than in the miR-26a mimic group and UVA group (both P < 0.05) , and lower in the UVA+miR-26a inhibitor group than in the miR-26a inhibitor group ( P < 0.05) , but significantly higher in the UVA+miR-26a inhibitor group than in the UVA group ( P < 0.05) . Conclusion:In the UVA irradiation-induced photoaging of skin fibroblasts, miR-26a expression was up-regulated, cellular proliferative activity and genome-wide methylation level decreased; up-regulation of miR-26a expression could down-regulate the expression of its target gene EZH2 and methylation-related gene DNM1, and promote cell photoaging, while down-regulation of miR-26a expression could up-regulate the expression of EZH2 and DNMT1, and inhibit cell photoaging.

Objective This study aimed to explore the effect of peripheral blood mesenchymal stem cells combined with porous absorbable gelatin sponge/self assembling peptide composite scaffolds on SD rat femoral con-dyle bone defect reconstruction and provide a new strategy for the repair of bone defects. Methods 30 female SD rats,8W age,were randomly divided into 3 groups,10 every group.The group A was blank control group,group B was porous absorbable gelatin sponge/self assembling peptide composite scaffold group,and group C was periph-eral blood mesenchymal stem cells combined with porous absorbable gelatin sponge/self assembling peptide compos-ite scaffold group. The effect of osteogenesis was observed by paraffin section,hematoxylin eosin staining,X-ray examination,and Micro-CT scanning in 3 dimensional reconstruction of femoral condyle defect. Results Imaging examination showed that the experimental group had better osteogenesis effect. Histological examination showed that a lot of new bone tissue was found in group C,while only a small amount of new bone was found in the group of A and B. Conclusions The experiment shows that peripheral blood mesenchymal stem cells as the seed cells for tissue engineering,combined with porous absorbable gelatin sponge-self assembling peptide has better ability to repair bone defects,and has good application prospect,which is worthy of further research.

Objective:To explore the feasibility and clinical results of absorbable antibacterial calcium sulfate combined with tissue flaps in the treatment of traumatic calcaneal osteomyelitis (CO) secondary to skin and soft tissue defects in children.Methods:From January 2007 to August 2020, 44 cases of children with heel skin and soft tissue defects associated with traumatic CO were treated and followed up effectively in the Third Affiliated Hospital of Xinxiang Medical University.Among them, 17 cases were treated with absorbable calcium sulfate cement combined with tissue flaps as the calcium sulfate group, and 27 cases were treated with antibiotic polymethylmethacrylate (PMMA) bead combined with tissue flaps as the membrane induction group.A comparison was drawn on the therapeutic effect, recurrence rate of postoperative infection, postoperative ankle mobility, number of operations, total length of hospital stays and hospitalization expenses between both groups.Results:The average follow-up time was 10.7 months in the calcium sulfate cement group and 9.3 months in the membrane induction group.All flaps were effective except for 3 cases who presented with small necrosis on the distal end of the sural neurovascular flaps.The recurrence rate of postoperative infection and the hospitalization expenses in the calcium sulfate group were lower than those in the membrane induction group, but the differences were not statically significant (all P>0.05). The postoperative ankle mobility [(63.6±9.3)°], number of operations [2(1.0, 2.0) times] and total length of hospital stay [6.1(4.5, 7.4) weeks] of the calcium sulfate group were significantly lower than those of the membrane induction group [(57.7±9.5)°, 2(2.0, 3.0) times, 7.0(5.0, 9.0) weeks], the difference were statistically significant (all P<0.05). Severe CO may cause structural damage to calcaneal tubercle or insertion site of achilles tendon, but the active plantar flexion function of ankles will be good despite the decrease in strength. Conclusions:The effect of absorbable antibacterial calcium sulfate cement combined with tissue flaps in the treatment of traumatic CO in children is favorable, and the number of operations, length of hospital stays and hospitalization expenses are relatively less compared with PMMA cement combined with tissue flaps.

Guizhi Mahuang Geban Tang derived from ZHANG Zhongjing's Treatise on Cold Damage is included in the Catalogue of Ancient Classic formulas （the second batch） issued by the National Administration of Traditional Chinese Medicine. By reviewing the ancient literature related to Guizhi Mahuang Geban Tang， this study analyzed the origin， medicinal composition， original plants and processing， dosage， decocting method， compatibility， effects， and indications of this formula. A total of 186 records of Guizhi Mahuang Geban Tang were obtained， involving 108 ancient books of traditional Chinese medicine. There are 6 synonyms of Guizhi Mahuang Geban Tang. This formula consists of Cinnamomi Ramulus， Paeoniae Radix Alba， Zingiberis Rhizoma Recens， Glycyrrhizae Radix et Rhizoma， Ephedrae Herba， Jujubae Fructus， and Armeniacae Semen Amarum， the original plants and processing of which are clear. With consideration to the dosage in modern clinical practice， it is recommended that the formula should be composed of 7.67 g Cinnamomi Ramulus， 4.60 g Paeoniae Radix Alba， 4.60 g Zingiberis Rhizoma Recens， 4.60 g Glycyrrhizae Radix et Rhizoma， 4.60 g Ephedrae Herba， 4.00 g Jujubae Fructus， and 2.60 g Armeniacae Semen Amarum. The decoction should be prepared by boiling Ephedrae Herba with 1 000 mL water for 15 min before the addition of other medicines， and the mixture was decocted to reach a volume of 360 mL， and 120 mL of the decoction should be taken warm once. Guizhi Mahuang Geban Tang is a combination of Guizhi Tang and Mahuang Tang， with the effects of dispersing wind cold and harmonizing nutrient-defense. The main diseases treated by this formula in the past dynasties have expanded compared with those in Treatise on Cold Damage. The traditional indications of this formula involve the diseases of greater Yang， reverting Yin， Yang brightness， and lesser Yin. In addition to common cold due to wind-cold， this formula can be used to treat headache， bitter mouth， dry throat， full abdomen， panting， heat invading blood chamber in women， skin itching， exanthema variolosum， syncope， and hardly perceivable pulse. In modern clinical practice， Guizhi Mahuang Geban Tang is used for treating pulmonary diseases such as upper respiratory tract infection， skin diseases （e.g.， urticaria， eczema， psoriasis， and neurodermatitis）， kidney failure， and diabetes complicated with pruritus.

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).