Neurodegenerative diseases are a collective term for a large group of diseases caused by degenerative changes in nerve cells. Aging is the main risk factor for neurodegenerative diseases. The neurovascular unit(NVU) is the smallest functional unit of the brain, which regulates brain blood flow and maintains brain homeostasis. Accelerated aging of NVU cells directly impairs NVU function and leads to the occurrence of various neurodegenerative diseases. The intrinsic mechanisms of NVU cell aging are complex and involve oxidative stress damage, loss of protein homeostasis, DNA damage, mitochondrial dysfunction, immune inflammatory response, and impaired cellular autophagy. In recent years, studies have found that traditional Chinese medicine(TCM) can inhibit NVU aging through multiple pathways and targets, exerting a brain-protective effect. Therefore, this article aimed to provide a theoretical basis for further research on TCM inhibition of NVU cell aging and references for new drug development and clinical applications by reviewing its mechanisms of anti-aging, such as regulating relevant proteins, improving mitochondrial dysfunction, reducing DNA damage, lowering inflammatory response, antioxidant stress, and modulating cellular autophagy.
Humans ; Medicine, Chinese Traditional ; Neurodegenerative Diseases/drug therapy* ; Brain ; Aging ; Neurons ; Blood-Brain Barrier

Objective To explore whether superovulation impairs the process of pregnancy establishment in mice by changing the intrauterine environment. Methods The implantation and pregnancy of superovulated and normal mice were compared. The superovulated mice were subjected to unilateral tubal ligation on day 0. 5 and blastocysts were transplanted to the other uterine horn on day 2. 5. The number of implantation sites of bilateral uterine horn was compared. The differences between preimplantation uteri of superovulated and normal pseudopregnancy mice were compared by tissue sections and high-throughput sequencing. Bioinformatics analysis was performed on the differentially expressed genes in two groups. Results Compared with the control group, the pregnancy rate of mice in the superovulation group decreased significantly. The number of implantation sites in the superovulation group was higher than the control. There was no significant difference in the pregnancy rate of the uterine horn between the control side and the transplanted side of the superovulated mice. The endometrium was thinned and the number of glands was reduced in superovulated pseudopregnancy mice. The gene expression patterns of preimplantation uterus in superovulation pseudopregnancy and normal pseudopregnancy mice were different. There were 1097 significantly differentially expressed genes, including 752 up-regulated genes and 345 down-regulated genes. Bioinformatics analysis showed that differentially expressed genes are mainly involved in biological processes, such as decidualization, response to progesterone, positive regulation of angiogenesis. They were mainly enriched in FoxO signaling pathway, cell cycle pathway and steroid biosynthesis pathway. Conclusion Superovulation impaired the process of establishing pregnancy and altered the gene expression patterns of biomarker of uterine receptivity in mice.

ObjectiveTo investigate the consistency of the brain structure volume estimation based on Synthetic MRI （SyMRI） and T1-FSPGR images in healthy children and youths. MethodsWe prospectively collected the brain SyMRI and T1-FSPGR images of 38 healthy children with age range of 6~13 years old and 30 healthy youths with age range of 22~26 years old. The Sythetic MR software and FreeSurfer software were used to measure the total gray matter volume （GMV）， total white matter volume （WMV）， brain parenchyma volume （BPV） and intracranial volume （ICV） based on SyMRI and T1-FSPGR images respectively. Paired t test， Pearson’s correlation analysis and interclass correlation coefficient （ICC） were used to evaluate the association between SyMRI and T1 derived measurements. ResultsThe volumes estimated by two methods in two groups showed differences in paired t test （P＜0.05）. Nevertheless， both in children and youths， the measurements of GMV， WMV， BPV and ICV all showed noticeable correlation and consistency between the two brain volume estimation methods ［r values are 0.691， 10.577， 0.938， 0.796 in children group and 0.657， 0.623， 0.933， 0.881 in adult group， P＜0.001； ICC95%CIs are 0.816 （0.647， 0.905）， 0.732 （0.484， 0.861）， 0.968 （0.938， 0.983） and 0.880 （0.770， 0.938］ in children group and 0.751 （0.476， 0.881）， 0.760 （0.496， 0.886）， 0.962 （0.920， 0.982）， and 0.936 （0.866， 0.970）in youth group］. ConclusionsThe brain segmentation and volume estimation based on SyMRI can acquire the measurements which have statistical difference but powerful association with that acquired from T1-FSPGR images， which suggests this new method have a good prospect for clinical use and scientific research.

OBJECTIVE: To compare the safety of low-dose cyclophosphamide and high-dose cyclophosphamide in the treatment of systemic lupus erythematosus (SLE). METHODS: A total of 1 022 patients with systemic lupus erythematosus from 24 hospitals in China between March 2017 to July 2018 were enrolled. Their clinical manifestations, laboratory tests, adverse events, reasons for stopping receiving intravenous cyclophosphamide and comorbidities were collected. Among them, 506 SLE patients received short-interval low-dose intravenous cyclophosphamide therapy (SILD IV-CYC, 400 mg every two weeks), and 256 patients underwent high-dose cyclophosphamide therapy (HD IV-CYC, 500 mg/m² of body surface area every month), the side effects between the two groups were compared, the remaining 260 SLE patients were treated with IV-CYC irregularly. Moreover, a total of 377 patients in SILD IV-CYC group and 214 patients in HD IV-CYC group had medical records of the reasons for stopping recei-ving IV-CYC. The reasons for stopping receiving IV-CYC in these two groups were analyzed. RESULTS: In this study, only 40.27%(238/591)of the SLE patients stopped receiving intravenous cyclophosphamide for the causes of disease improvement, however, up to 33.67% (199/591) of the patients for the reason of drug-related side effects. There were 83 patients out of 214 (38.79%) with high-dose intravenous cyclophosphamide treatment who stopped receiving IV-CYC for the drug-related side effects, which was significantly higher than that in the low-dose cyclophosphamide group (30.77%, 116/337, P=0.048). Of theses 506 patients in SILD IV-CYC group, 88 (17.39%) patients experienced gastrointestinal reactions, 66 (13.04%) suffered from infections, 49 (9.68%) had myelosuppression and 68 (13.44%) had alopecia, respectively. Among the 256 patients in the HD IV-CYC group, 80 (31.25%) experienced gastrointestinal reactions, 57 (22.27%) suffered from infections, 51 (19.92%) had myelosuppression and 49 (19.14%) had alopecia. Moreover, 71 (25.18%) of 282 female patients with age between 16 to 45 years in SILD IV-CYC group had abnormal menstruation, while menstrual disorder occurred in 39.72% (56/141) patients of HD IV-CYC group. There was no difference of drug-induced hepatic injury, hemorrhagic cystitis and fatigue between the two groups. CONCLUSION Low-dose cyclophosphamide showed a lower prevalence of adverse events than high-dose cyclophosphamide in systemic lupus erythematosus patients.
Humans ; Female ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Immunosuppressive Agents/adverse effects* ; Cyclophosphamide/therapeutic use* ; Lupus Erythematosus, Systemic/drug therapy* ; Administration, Intravenous ; Alopecia/drug therapy*

Objective:To evaluate the clinical efficacy and safety of Longmu Zhuanggu granule for the treatment of children recurrent respiratory infection due to lung-spleen Qi deficiency. Method:This multicenter stratified， block-randomized， double-blind， double-dummy， positive drug （pidotimod granule） parallel controlled， and non-inferiority trail intended to included 240 children patients and divided them into the experimental group （n=120） and the control group （n=120） at the ratio of 1∶1. Patients in both groups were treated for eight successive weeks and followed up for 12 months. The cure rates， numbers of respiratory infections， average courses of disease， curative effects of traditional Chinese medicine （TCM） syndrome， curative effects of individual symptoms， curative effects of immune indexes， and safety indexes between the two groups were observed and compared. Result:A total of 237 subjects were collected from 10 research centers， including 119 cases in the control group and 118 in the experimental group. There were 236 cases enrolled into the full analysis set （FAS）， 210 into the per-protocol set （PPS）， and 236 into the safety set （SS）. The baseline data of the two groups were not significantly different from each other， indicating that they were comparable. The cure rates of the experimental group and control group were 75.21% （88/117） and 73.95%（88/119）， respectively， with the 95% confidence interval （CI） of difference between the two groups being 1.26% （-9.85%，12.37%） for FAS and 3.81% （-6.28%，13.90%） for PPS. The 95% CI fell within the 10% non-inferiority margin， implying that non-infertility test of the cure rate in the treatment of endpoint disease was valid， and the conclusions of FAS and PPS analysis were consistent. There was no significant difference in the number or course of upper respiratory infection， bronchitis， and pneumonia. The difference in curative effects of TCM syndrome between the two groups after four weeks of treatment was not remarkable. After eight weeks of treatment， the total effective rate of the experimental group was 84.62%（99/117）， statistically higher than 78.15%（93/119） of the control group（χ²=-3.26，P<0.05）. There were no significant differences in the disappearance rates of individual symptoms between the two groups after four weeks of treatment. After eight weeks of treatment， the experimental group and control group exhibited the disappearance rates of 67.50%（54/80） and 47.37%（36/76） for shortness of breath and laziness to speak， 75.00%（54/72） and 53.33%（40/75） for poor appetite， 54.55%（60/110） and 37.84%（42/111） for hyperhidrosis， respectively， with obviously better outcomes observed in the experimental group （P<0.05，P<0.01）. The inter-group comparison revealed significant differences in immune indexes after eight weeks of treatment. As demonstrated by comparison with the situations before treatment， IgA， IgG， IgM， and CD4 did not change significantly after treatment. Except for CD8 in the experimental group (P<0.05), there was no significant difference in other immune indexes before and after treatment There was no significant difference in the incidence of adverse reactions. Conclusion:Longmu Zhuanggu granule is not inferior to pidomod granule in the treatment of children recurrent respiratory infection due to lung-spleen Qi deficiency， and it exhibits good safety， implying its promising clinical application value.

Purpose To investigate the expression and clinical significance of free fatty acid receptor 4 (FFAR4) in hepatocellular carcinoma (HCC) . Methods The expression of FFAR4 in HCC tissues and adjacent tissues of HCC patients was confirmed by 102 cases of liver resection and postoperative pathology, and the relationship between FFAR4 expression and clinical data of HCC patients was analyzed. Quantitative realtime PCR (qRT-PCR) and Western blot were used to detect the expression of FFAR4 in 20 pairs of freshly frozen HCC and adjacent tissues,and the related literatures were reviewed. Results The expression rate of FFAR4 in HCC tissues was 64. 7％ (66/102) ,and that in adjacent tissues was 15. 7％ (16/102) . The difference in FFAR4 expression between the two groups was statistically significant (P < 0. 05) . The high expression of FFAR4 in HCC tissues was significantly correlated with tumor vascular invasion (P < 0. 05) ,TNM stage (P < 0. 01) ,and Edmondson classification (P < 0. 05) . qRT-PCR and Western blot showed that the expression of FFAR4 in HCC tissues was significantly higher than that in adjacent tissues. The difference between the two groups was statistically significant (P < 0. 01,P< 0. 05) . Conclusion The expression of FFAR4 is significantly associated with the presence of vascular invasion,TNM staging, and Edmondson grading in HCC. High expression of FFAR4 may be closely related to the severity of HCC patients.

Objective To systematically review the value of enhanced recovery after surgery(ERAS)in the perioperative period of hepatec-tomy. Methods A literature search was conducted in PubMed,Embase,Cochrane Library,Sinomed,Wanfang Data,VIP,and CNKI to iden-tify the articles on the application of ERAS in the perioperative period of hepatectomy published up to July 2017. Quality evaluation and data extraction were performed for the included articles. A Meta - analysis was performed using Revman 5.3 software. Results A total of 17 articles were included,with 14 randomized controlled trials and 3 controlled clinical trials. A total of 2220 patients were involved and divided into ERAS group(n=1002)and control group(n=1218). Compared with the control group,the ERAS group had significantly shortened length of postoperative hospital stay(weighted mean difference[WMD]= -2.58,95% confidence interval[CI]:-3.47 to-1.70,P<0.05),functional rehabilitation time(WMD= -3.39,95%CI:-4.32 to -2.45,P<0.05),and time to first flatus(standardized mean difference[SMD]= -1.56,95%CI:-2.15 to -0.97,P<0.05),as well as reduced complication rate(odds ratio[OR]=0.64,95%CI:0.52-0.78,P<0.05)and hospital costs(SMD= -0.85,95%CI:-1.23 to -0.47,P<0.05).There were no significant differences between the two groups in readmission rate(OR =1.28,95%CI:0.69 -2.69,P > 0.05),operation time(WMD = -11.36,95%CI:-23.25 to 0.53,P>0.05),and intraoperative blood loss(WMD= -22.62,95%CI:-38.89 to -6.34,P>0.05).Conclusion ERAS is safe and effective in the perioperative period of hepatectomy and holds promise for clinical application.

Objective To investigate the expression and clinical significance of aquaporin-1 (AQP-1) and E-cadherin in hepatocellular carcinoma tissues.Methods From June 2005 to June 2015,paraffin specimens from 30 hepatocellular carcinoma patients underwent surgical treatment and 19 cases of normal liver were collected in our hospital.Immunohistochemistry assay was used to detect the expression of AQP-1 and E-cadherin in 30 cases of hepatocellular carcinoma tissues and 19 cases of normal tissues.Results The positive rates of AQP-1 in hepatocellular carcinoma tissues and normal liver tissues were 66.67％ (20 cases/30 cases) and 42.11％ (8 cases/19 cases)respectively.The positive rate of E-cadherin in hepatocellular carcinoma tissues and normal liver tissues were 33.33％ (10 cases/30 cases) and 100.00％ (19 cases/19 cases)respectively,and the difference between two groups was statistically significant (P ＜ 0.05).And expression of AQP-1 had inverse correlation to E-cadherin (r =-0.40,P ＜ 0.05).Conclusion The abnormal expression of AQP-1 and E-cadherin may play an important role in the process of development and metastasis of hepatocellular carcinoma.

Aged ; Biopsy ; methods ; Bronchoscopy ; methods ; Cryptogenic Organizing Pneumonia ; diagnosis ; Female ; Humans ; Image-Guided Biopsy ; methods ; Lung ; pathology ; Male ; Middle Aged ; Ultrasonography ; methods

Objective: To investigate the expression and effect of secreted frizzled-related protein 5 (sFRP5) in rat's cardiomyocyte hypertrophy in vitro. Methods: Neonatal rat's ventricular myocytes were cultured in vitro, cardiomyocyte hypertrophy was induced by Ang Ⅱ. Telmisartan and PD123319 were used to block angiotensin type 1 receptor (AT1R) and angiotensin type 2 receptor (AT2R) respectively. RT-PCR and Western-blot analysis were conducted to examine the expressions of sFRP5, BNP and TNF-α. Results: sFRP5 was expressed in cardiomyocytes. The mRNA and protein expressions of sFRP5, protein expression of BNP were increased by prolonged time of AngⅡ treatment, the maximum expression was observed at 48 h, P<0.05. Compared with Ang Ⅱ (10-6mol/L) group, the mRNA and protein expressions of sFRP5 in Ang Ⅱ +Telmisartan (10 μmol/L) group were decreased, P<0.05, those expressions were similar in Ang Ⅱ +PD123319 (10 μmol/L) group, P>0.05. Compared with AngⅡ (10-6 mo1/L)+sFRP5 (0 ng/ml) group, protein expressions of BNP and TNF-α were decreased inAng Ⅱ (10-6 mo1/L)+sFRP5 (10 ng/ml) group and in Ang Ⅱ (10-6 mo1/L)+sFRP5 (100 ng/ml) group respectively, P<0.05. Conclusion: For in vitro process of Ang Ⅱ induced neonatal rat's cardiomyocyte hypertrophy, using Ang Ⅱ receptor could up-regulate sFRP5 expression and sFRP5 plays an important role in cardiomyocyte hypertrophy.