Objective:To investigate the hepatoprotective effect of N-acetylcysteine(NAC)on rats with liver injury induced by cisplatin and its effect on intestinal flora and the expression of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and nuclear factor-kappa B(NF-κB).Methods:Male Sprague-Dawley rats were randomly divided into control group(CG),cisplatin group(CP),and NAC group.The rats in the NAC group were given NAC 15 mg/kg by gavage for 8 consecutive days.At half an hour after intragastric administration on the fifth day,all rats except those in the NC group were given intraperitoneal injection of 8 mg/kg cisplatin to induce acute liver injury.An automatic biochemical analyzer was used to measure the content of aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(ALP),and total bilirubin(TBIL);liver index was calculated for the rats;Western blot was used to measure the relative expression levels of NF-κB,IL-6,and TNF-α in liver tissue;the 16S rDNA technique was used to measure and analyze the amplification information of the V3-V4 regions of each sample.Results:Compared with the NC group,the CP group had significant increases in the content of AST,ALT,ALP,and TBIL,while NAC reversed the abnormal liver function caused by cisplatin.Compared with the NC group,the CP group had a sig-nificant increase in liver index(P=0.000),while the NAC group had a significant reduction in liver index compared with the CP group(P=0.007).Compared with the NC group,the CP group had signifi-cant increases in the expression levels of IL-6,TNF-α,and NF-κB,while the NAC group showed reductions in the expression of these genes,with significant differences in the expression of IL-6 and TNF-α(P=0.006 and 0.000).Compared with the NC group,the CP group had a significant increase in the α-diversity index of intesti-nal flora,while compared with the CP group,the NAC group tended to have a reduction in the α-diversity index of intestinal flora.Com-pared with the CP group at the phylum level,the NAC group had an increase in the abundance of Actinobacteria and a reduction in the abundance of Firmicutes.Compared with the CP group at the genus level,the NAC group had a reduction in the abundance of Rumino-coccaceae and increases in the abundance of Bifidobacterium and Allobaculum.Conclusion:NAC can alleviate acute liver injury caused by cisplatin,possibly by downregulating the expression of IL-6,TNF-α,and NF-κB and regulating the abundance and diver-sity of intestinal flora.

Mandibular defects caused by injuries, tumors, and infections are common and can severely affect mandibular function and the patient's appearance. However, mandible reconstruction with a mandibular bionic structure remains challenging. Inspired by the process of intramembranous ossification in mandibular development, a hierarchical vascularized engineered bone consisting of angiogenesis and osteogenesis modules has been produced. Moreover, the hierarchical vascular network and bone structure generated by these hierarchical vascularized engineered bone modules match the particular anatomical structure of the mandible. The ultra-tough polyion complex has been used as the basic scaffold for hierarchical vascularized engineered bone for ensuring better reconstruction of mandible function. According to the results of in vivo experiments, the bone regenerated using hierarchical vascularized engineered bone is similar to the natural mandibular bone in terms of morphology and genomics. The sonic hedgehog signaling pathway is specifically activated in hierarchical vascularized engineered bone, indicating that the new bone in hierarchical vascularized engineered bone underwent a process of intramembranous ossification identical to that of mandible development. Thus, hierarchical vascularized engineered bone has a high potential for clinical application in mandibular defect reconstruction. Moreover, the concept based on developmental processes and bionic structures provides an effective strategy for tissue regeneration.
Bone Regeneration ; Bone Transplantation/methods* ; Hedgehog Proteins ; Humans ; Mandible/surgery* ; Osteogenesis

In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.

Objective To evaluate whether the thalamic paraventricular nucleus mediates orexiner-gic ( orexin ) neurons-induced promotion of emergence from general anesthesia by using the optogenetics method in mice. Methods Twenty healthy male Hcrt-cre mice, aged 8-10 weeks, weighing 20-25 g, were divided into 4 groups ( n=5 each) using a random number table method: retrograde labeled viruses channelrhodopsin group ( R group) , anterograde labeled viruses channelrhodopsin group ( A group) , retro-grade labeled viruses control group ( RC group ) , and anterograde labeled viruses control group ( AC group) . The optogenetics technique was used in each group. Anesthesia was induced and maintained through inhaling 1％ isoflurane and pure oxygen 1. 0 L∕min. Electroencephalogram was monitored througout the procedure with the PowerLab monitoring system. The burst suppression ratio ( BSR) was recorded at 1 min before light stimulation and during light stimulation. Results Compared with RC group or the baseline at 1 min before light stimulation, the BSR was significantly decreased during light stimulation in R group ( P<0. 05) . Compared with AC group or the baseline at 1 min before light stimulation, the BSR was signifi-cantly decreased during light stimulation in group A ( P<0. 05) . Conclusion Optogenetics technique ap-plication once again confirms that orexin neurons can promote emergence from general anesthesia through thalamic paraventricular nucleus in mice.

Objective: To screen the differentially expressed long non-coding RNAs(lncRNAs) by analyzing the related gene sequencing data of female non-smoking lung cancer patients in the database of The Cancer Genome Atlas (TCGA). Methods: The gene expression data and the corresponding clinical information of female non-smoking lung cancer patients were downloaded from the TCGA database. Then, the data were processed, integrated and analyzed with the R software package, and the differentially expressed genes were screened out. The prognosis was analyzed by the Survival package. Results: A total of 354 differentially expressed lncRNAs associated with female non-smoking lung cancer were obtained, of which 45 were down-regulated and 309 were up-regulated in tumor tissues. The prognosis analysis showed that the expression level of LINC01863 was positively correlated with the prognosis of female non-smoking lung cancer patients (P＜0.05), and that the expression levels of LINC02487, LINC01419 and DSCAM-AS1 were negatively correlated with the prognosis of female non-smoking lung cancer patients (P＜0.05). Conclusion The re-analysis on the high-throughput sequencing data in TCGA database obtains a large number of lncRNAs related to the development of female non-smoking lung cancer, which provides the potential new targets for the diagnosis and prognosis assessment of female non-smoking lung cancer.

There is a high incidence of adult chronic obstructive pulmonary disease (COPD),which induces high rate of disability,and heavy financial burden in China.As the core of comprehensive treatments of COPD,lung rehabilitation can improve the quality of life and reduce the cost of treatment.This article introduces not only the definition of COPD lung rehabilitation and its recent states and progress,but also the related indications of different lung rehabilitation techniques with the formulations and resolutions of rehabilitation programs.

Objective: To investigate the histone acetylation level and histone deacetylase (HDAC) activity of peripheral blood CD4+ T lymphocytes in patients with oral lichen planus (OLP). Methods : Twenty-three OLP patients were selected from August 2016 to January 2017 from the Stomatological Hospital, Southern Medical University. The diagnosis was confirmed by pathology, and the lesions were divided into a nonerosive OLP group (11 cases) and an erosive OLP group (12 cases). Ten healthy sex- and age-matched volunteers served as controls. Immunomagnetic beads were used to separate CD4+ T lymphocytes, and histones and nucleoproteins were extracted. The global histone H3/H4 acetylation levels and HDAC activity of CD4+ T lymphocytes from all subjects were detected by ELISA. The differences between the OLP and control groups were statistically analyzed. Results: Global histone H3 hypoacetylation was observed in the OLP group compared with the control group (u = -2.410, P = 0.012). However, there was no significant difference in the serum CD4+ T lymphocyte histone H4 acetylation level between the OLP and control group (u = -1.412, P = 0.158). HDAC activity was significantly higher in the OLP group than in the healthy control group (F = 5.749, P = 0.023), and much higher HDAC activity was observed in the erosive group than in the nonerosive (P = 0.014) and healthy control groups (P = 0.001). The degree of histone H3 acetylation correlated negatively with increased HDAC activity in the OLP group (rs = -0.771, P < 0.001). There was no correlation between the level of histone H3 acetylation and HDAC activity in the healthy control group (rs = 0.382,P = 0.276). The histone H4 acetylation level in the OLP group showed no correlation with HDAC activity (rs = 0.149, P = 0.498), and the histone H4 acetylation level in the control group also showed no correlation with HDAC activity (rs = 0.527, P = 0.117). Conclusion Abnormal histone acetylation of CD4+ T lymphocytes in the peripheral blood of patients with OLP was identified and could be related to HDAC activity, suggesting that the epigenetic modification of histone acetylation may play a role in the pathogenesis of OLP.

Objective: To recognize the efficacy and safety of paritaprevir/ritonavir-ombitasvir combined with dasabuvir (OBV/PTV/RTV+DSV) in the treatment of genotype 1b chronic hepatitis C. Methods: Patients with genotype 1b chronic hepatitis C who were admitted to the People's Hospital of Henan Province, Huashan Hospital of Shanghai and the Fifth Medical Center of the General Hospital of the People's Liberation Army of China between November 2017 to August 2018 were enlisted. All patients received OBV/PTV/RTV+DSV antiviral therapy. HCV RNA levels were measured at baseline, weeks 1, 2, 3, 4, 8, 12, and 24, then 12 weeks, and 24 weeks after completion of treatment; patients’ comorbidity, concomitant medications, and clinical adverse events were recorded. Results: 108 patients were enrolled in the study, with an average age of 49.1 years, 44 patients were male (40.8%), 96.3% (104/108) were newly diagnosed, and four patients had previous treatment history, of whom three were treated with IFN and one with IFN + DAA. Ninety-eight cases completed 12 weeks treatment and 89 cases were in follow up for 12 weeks, after discontinuation of the drug. Overall, 89 cases (100%) achieved SVR12.One patient treated with PR and DAA had HCV RNA level of 869175 IU/mL at 4 weeks of treatment, which was significantly higher than the baseline HCV RNA level (301776IU/ML), and was judged as failure of treatment; and follow-up was discontinued. Of all enrolled patients, 19 (17.6%) had underlying diseases and 15 (13.9%) had combined medications. During treatment, adverse events (AE) occurred in 11 patients (10.1%). The main adverse events were pruritus and elevated bilirubin. Conclusion Combined antiviral therapy (OBV/PTV/RTV+DSV) of 12 weeks are highly effective with good safety profile in the treatment of Chinese patients with genotype 1b chronic hepatitis C.

Objective To investigate association of vitamin D receptor (VDR) polymorphisms with susceptibility to psoriasis vulgaris and clinical response to calcipotriol in patients with psoriasis vulgaris.Methods A total of 110 patients with psoriasis vulgaris and 183 healthy controls were enrolled into this study,and they were all of Han nationality from Hainan province.Ligase detection reaction (LDR) was conducted to determine the genotypes of VDR gene polymorphisms rs2228570,rs731236,rs1544410 and rs7975232.Single nucleotide polymorphism (SNP)-based association analysis in genotypic and allelic models,and haplotype-based association analysis were then performed.Then,75 patients with psoriasis area and severity index (PASI) scores less than 10 were topically treated with calcipotriol ointment alone.After 6-week treatment,the efficacy of calcipotriol ointment was evaluated,and the correlation between the efficacy and individual genotypes was analyzed.Results The frequency of A allele of rs7975232 in the psoriasis group and control group was 39.09％ and 27.05％ respectively,and the risk of developing psoriasis in rs7975232 A allele carriers was significantly higher than that in non-carriers (OR =1.731,95％ CI:1.213-2.471,P ＜ 0.05).Additionally,the risk of developing psoriasis in individuals with AA genotype (OR =2.404,95％ CI:1.085-5.328,P ＜ 0.05),as well as in individuals with AC genotype (OR =2.143,95％ CI:1.283-3.579,P ＜ 0.05),was significantly higher than that in patients with CC genotype.CTGA haplotype carriers (rs2228570,rs731236,rs1544410,rs7975232,respectively) had significantly higher risk of developing psoriasis compared with non-carriers (OR =1.907,95％ CI:1.132-3.214,P ＜ 0.05).Among 72 patients with mild-to-moderate psoriasis whose PASI scores were less than 10,patients with CC genotype of rs7975232 showed better response to calcipotriol ointment compared with those with AC genotype (OR =3.798,95％ CI:1.061-13.590,P ＜ 0.05) and those with AA genotype (OR =9.667,95％CI:1.556-60.040,P ＜ 0.05).Conclusion VDR polymorphisms are associated with psoriasis susceptibility and clinical response to calcipotriol in patients with psoriasis individuals.

Objective To evaluate the additional efficacy of local anesthetic injection (LAI) as a part of multimodal anal?gesia in patients undergoing total knee arthroplasty (TKA) with respect to pain, narcotic use, knee function and complications. Methods A multicenter randomized, controlled, double blind study was performed. A total of 101 patients undergoing unilateral TKA in two centers were randomly divided into injection group and control group. Injection group (50 cases) received local anes?thetic injection of ropivacaine (200 mg), fentanyl (1μg) and epinephrine (1∶1 000, 0.25 mg) in operation and control group (51 cas?es) did not. All patients received standardized general anesthesia and postoperative intravenous patient controlled analgesia (PCA). Preoperative baseline data, surgery?related conditions, postoperative pain (on a 0 to 10 scale), knee function, time of open?ing PCA, narcotic dosage in PCA and complications were compared respectively. Results The time of opening PCA in injection group (4-10 h, M=8 h) was longer than that in control group (2-5 h, M=4 h) (P<0.05). The 12 h, 24 h and total narcotic use of PCA in injection group (8.62±3.601 ml, 21.22±9.220 ml, 38.52±7.764 ml) was less than that in control group (18.43±9.671 ml, 35.30± 11.414 ml, 55.52±12.405 ml) (P<0.05). At post anesthesia care unit the mean VAS in injection group (2.40±1.927) was lower than that in control group (3.06 ± 2.073) (P<0.05). There was no difference in mean VAS at other time points, knee function, length of stay between two groups (P>0.05). Conclusion LIA in TKA can relieve pain early after TKA, prolong the time of opening PCA and reduce narcotic use compared with patients without it. It is simple and safe to use.