Angelica sinensis Polysaccharide and Astragalus membranaceus Polysaccharide Accelerate Liver Regeneration by Enhanced Glycolysis via Activation of JAK2/STAT3/HK2 Pathway.

The promotion of liver regeneration is crucial to avoid liver failure after hepatectomy. Angelica sinensis polysaccharide (ASP) and Astragalus membranaceus polysaccharide (AMP) have been identified as being associated with hepatoprotective effects. However, their roles and specific mechanisms in liver regeneration remain to be elucidated. In the present study, it suggested that the respective use of ASP or AMP strikingly promoted hepatocyte proliferation in vitro with a wide range of concentrations (from 12.5 µg/mL to 3200 µg/mL), and a stronger promoting effect was observed in combined interventions. A significantly enhanced liver/body weight ratio (4.20%) on day 7 and reduced serum transaminase (ALT 243.53 IU/L and AST 423.74 IU/L) and total bilirubin (52.61 IU/L) levels on day 3 were achieved by means of ASP-AMP administration after partial hepatectomy in mice. Metabonomics showed that differential metabolites were enriched in glycolysis with high expression of beta-d-fructose 6-phosphate and lactate, followed by significantly strengthened lactate secretion in the supernatant (0.54) and serum (0.43) normalized to control. Upon ASP-AMP treatment, the knockdown of hexokinase 2 (HK2) or inhibited glycolysis caused by 2-deoxy-d-glucose decreased hepatocyte proliferation in vitro and in vivo. Furthermore, pathway analysis predicted the role of JAK2/STAT3 pathway in ASP-AMP-regulated liver regeneration, and phosphorylation of JAK2 and STAT3 was proven to be elevated in this promoting process. Finally, downregulated expression of HK2, an attenuated level of lactate secretion, and reduced hepatocyte proliferation were displayed when STAT3 was knocked out in vitro. Therefore, it can be concluded that ASP-AMP accelerated liver regeneration and exerted a hepatoprotective effect after hepatectomy, in which the JAK2/STAT3/HK2 pathway was actively involved in activating glycolysis.

ALDH1 Expression and the Prognosis of Lung Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: Aldehyde dehydrogenase 1 (ALDH1) has been identified as a putative cancer stem cell (CSC) marker in lung cancer. However, the clinicopathological and prognostic value of this protein in lung cancer patients remains controversial. Thus, we performed a systematic review and meta-analysis of studies assessing the clinical and prognostic significance of ALDH1 expression in lung cancer. METHODS: An identification and review of publications assessing clinical or prognostic significance of ALDH1 expression in lung cancer until September 1, 2014 was undertaken. A meta-analysis was performed to clarify the association between ALDH1 expression and clinical outcomes. RESULTS: A total of 14 publications met the criteria and comprised 1926 cases. Analysis of these data showed that ALDH1 expression was not significantly associated with the patient age (OR = 0.82, 95% confidence interval [CI]: 0.45-1.50, P=0.52), tumour size (OR=0.68, 95% CI: 0.22-2.06, P=0.49), smoking status (OR=1.37, 95% CI: 0.85-2.22, P=0.19), or tumour grade (OR=1.65, 95% CI: 0.83-3.26, P=0.15). However, in the identified studies, ALDH1 expression was highly correlated with lymph node metastasis (OR=1.97, 95% CI: 1.16-3.34, P=0.01), tumour TNM staging (OR=1.68, 95% CI 1.28-2.22, P=0.0002), decreased overall survival (relative risk [RR]: 1.97,95% CI: 1.16-3.34, P =0.01) and decreased disease free survival (RR: 1.63, 95% CI: 1.01-2.64, P=0.05). CONCLUSIONS: This meta-analysis shows ALDH1 expression in lung cancer is connected with decreased overall and disease free survival and thus marks a worse prognosis.

[Effect of Sanhuang Yilong Decoction combined MTX on the expression of serum IL-1, IL-6, and IL-17 in rheumatoid arthritis patients of accumulated dampness-heat syndrome].

OBJECTIVE: To study the effect of bitter-cold herbs easing dampness method (BCHEDM) plus Sanhuang Yilong Decoction (SYD) combined with methotrexate (MTX) on expression levels of interleukin-1 (IL-1), IL-6, and IL-17 in rheumatoid arthritis (RA) patients of accumulated dampness-heat syndrome (ADHS). METHODS: From January 2011 to January 2013 recruited were 90 RA inpatients of ADHS at Department of Integrative Medicine on Rheumatoid Disease, General Hospital of Chengdu Military Region. They were assigned to the treatment group (45 cases) and the control group (45 cases) according to the random digit table produced by SPSS 11.5 Software. Patients in the treatment group were treated by heavy bitter-cold herbs plus SYD combined with MTX, while those in the control group were treated by MTX alone. Expressional levels of IL-1, IL-6, and IL-17 in serum were detected by enzyme linked immunosorbent assay (ELISA) before treatment, at week 2 and 4 after treatment. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and disease activity score in 28 joints (DAS28) were detected as well. RESULTS: After two or four weeks of treatment, ESR, CRP, and DAS28 decreased more in the treatment group than in the control group with statistical difference (P < 0.05, P < 0.01). After four weeks of treatment, IL-1, IL-6, IL-17, ESR, CRP, and DAS28 in the treatment group were all lower than before treatment and those of the control group at corresponding time points with statistical difference (P < 0.01). CONCLUSION: SYD combined MTX could play roles of improving inflammatory indices within 2 weeks, and inhibiting the expression of IL-1, IL-6, and IL-17 within 4 weeks.

[Protection and mechanism of shenqi compound for diabetic angiopathy model rats].

OBJECTIVE: To investigate the protective effect and mechanism of Shenqi Compound on diabetic angiopathy modeled rats. METHODS: Totally 18 SD rats were randomized into 3 groups, i.e., the normal control group, the diabetic mellitus (DM) group, and Shenqi Compound group, 6 in each group. The DM rat model was established by feeding high-fat diet (to induce hyperlipidemia) +intraperitoneal injection of small dose streptozotocin (STZ). Shenqi Compound was given to rats in the Shenqi Compound group at the daily dose of 2 g/kg. Equal volume of normal saline was given to rats in the model group and the normal control group by gastrogavage. All treatment was lasted for 12 weeks. Then 2-D and ultrasonic integrated backscatter technique were used to evaluate structural and functional changes of abdominal aorta in the progression of diabetic macroangiopathy. The fibrosis degree of the aorta vessel and myocardium capillaries were observed by using HE and Masson trichrome staining. The tension of the aortic vascular ring was determined. The transforming growth factor beta (TGF-beta) mRNA expression was detected by real time PCR (RT-PCR). The protein expression of TGF-beta, collagen I, collagen III, connective tissue growth factor (CTGF), and phosphorylation P38 MAPK were detected by Western blot. RESULTS: Compared with the normal control group, abdominal aortic systolic inner diameter, diastolic inner diameter, Peterson elastic modulus, stiffness index, and backscatter integral significantly increased; the rangeability of integral backscatter and the extension coefficient of cross section significantly decreased in the DM group (all P < 0.05). After 12 weeks aforesaid indices were obviously improved in the Shenqi Compound group (P < 0.05). Results of HE and Masson staining showed that the fibrosis degree of the aorta vessel and myocardium capillaries was obviously alleviated in rats of the Shenqi Compound group (P < 0.05). Results of the aortic vascular ring tension showed that acetylcholine induced vasodilatation and maximum diastolic percent were obviously elevated in the Shenqi Compound group (P < 0.05). Compared with the normal control group, the mRNA expression of TGF-beta, and the protein expression of TGF-beta, collagen I, and collagen III, and phosphorylation of P38 MAPK all significantly increased in the DM group (P < 0.05). Compared with the DM group, the mRNA expression of TGF-beta, and the protein expression of TGF-beta, collagen I, and collagen III, and phosphorylation of P38 MAPK all decreased (P < 0.05). CONCLUSIONS: Shenqi Compound could effectively improve the arterial function in diabetic marcoangiopathy and microvascular dysfunction. The mechanism might be due to the down-regulating the expression of TGF-beta, and further suppressing the phosphorylation of P38 MAPK, reducing the synthesis of collagen I and collagen III, therefore, ameliorating arterial and myocardial interstitial fibrosis.

[Correlation study between interleukin-17 and ESR and CRP in serum and the synovial fluid of rheumatoid arthritis patients of accumulated dampness-heat obstruction in joints syndrome].

OBJECTIVE: To probe the function of interleukin-17 (IL-17) in rheumatoid arthritis (RA) patients of accumulated dampness-heat obstruction in joints syndrome (ADOJS) by detecting levels of IL-17 in serum and the synovial fluid and analyzing its correlation with erythrocyte sedimentation rate (ESR) and C reactive protein (CRP). METHODS: From January 2011 to January 2013, recruited were 90 RA inpatients of ADOJS at Department of Integrative Medical Rheumatism, General Hospital of Chengdu Military Region, of which 28 patients had knee joint effusion. Besides, 30 healthy volunteers who received physical examination at our hospital were recruited as the normal control group, and 30 patients with osteoarthritis (OA) who had knee joint effusion were recruited as the synovial fluid control group. The expression levels of IL-17 in serum and the synovial fluid were detected by enzyme linked immunosorbent assay (ELISA), and contents of ESR and CRP were detected in RA patients. Then correlation analyses were performed between levels of IL-17 and contents of ESR and CRP. RESULTS: Compared with the normal serum control group, the expression levels of IL-17 in serum of RA patients significantly increased (P < 0.05). Compared with the serum of RA patients and the synovial fluid of OA patients, the expression levels of IL-17 in the synovial fluid of RA patients significantly increased (P < 0.05). The expression levels of IL-17 in serum of RA patients were not correlated with ESR or CRP (r = 0.092, -0.082; P > 0.05), and the expressional levels of IL-17 in the synovial fluid of RA patients were not correlated with ESR or CRP (r = 0.113, -0.034; P > 0.05). CONCLUSIONS: IL-17 was the main effector cytokine of Th17 cells. The expressional levels of IL-17 significantly increased in serum and the synovial fluid of RA patients of ADOJS, but with no correlation to ESR or CRP. It indicated that IL-17 participated in the occurrence and development of RA. Concrete mechanisms needed to be further proved in larger samples.

Effects of long-term exposure to high altitude on brain structure in healthy people: an MRI-based systematic review and meta-analysis.

Purpose: To conduct a systematic review and meta-analysis of observational studies of brain MRI, this paper assesses the effects of long-term exposure to high-altitude on brain structures in healthy people. Methods: Observational studies related to high-altitude, brain and MRI were systematically searched based on data retrieved from PubMed, Embase and Cochrane Library. The timescale for collecting literature was from the establishment of the databases to 2023. NoteExpress 3.2 was used to manage the literature. Two investigators performed literature screening and data extraction based on inclusion criteria, exclusion criteria, and literature quality. The quality of the literature was assessed using the NOS Scale. Finally, meta-analysis of included studies was performed using Reviewer Manager 5.3. Results: Initially, 3,626 articles were retrieved. After screening, 16 articles (n = 756 participants) were included in the systematic review, and meta-analysis was performed on 6 articles (n = 350 participants). The overall quality of the included articles was at medium level, with a mean NOS score of 5.62. The results of meta-analysis showed that the differences between the HA group and LA group were not statistically significant, in total GM volume (MD: -0.60, 95% CI: -16.78 to 15.58, P = 0.94), WM volume (MD: 3.05, 95% CI: -15.72 to 21.81, P = 0.75) and CSF volume (MD: 5.00, 95% CI: -11.10 to 21.09, P = 0.54).The differences between HA and LA in FA values of frontotemporal lobes were not statistically significant: right frontal lobe (MD: -0.02, 95% CI: -0.07 to 0.03, P = 0.38), left frontal lobe (MD: 0.01, 95% CI: -0.02 to 0.04, P = 0.65), right temporal lobe (MD: -0.00, 95% CI: -0.03 to 0.02, P = 0.78) and left temporal lobe (MD: -0.01, 95% CI: -0.04 to 0.02, P = 0.62). However, there were significant differences in GM volume, GM density and FA values in local brain regions between HA group and LA group. Conclusion: Compared with LA area, there were no significant differences in total GM, WM and CSF volumes in healthy people living at high-altitude area for long-term, while there were significant differences in GM volume and FA values in local brain regions. Long-term exposure to high-altitude area caused the adaptive structural changes in local brain regions. Since heterogeneity existed between the studies, further studies are needed to uncover the effects of high-altitude on brain of healthy people. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42023403491.

Effect of intubation in the lateral position under general anesthesia induction on the position of double-lumen tube placement in patients undergoing unilateral video-assisted thoracic surgery: study protocol for a prospective, single-center, parallel group, randomized, controlled trial.

BACKGROUND: The double-lumen tube (DLT) is an essential equipment for thoracic anesthesia and the precise position of DLT placement is particularly important for anesthesia and surgery. However, the incidence of DLT malposition remains high and it leads to lung isolation failure and hypoxemia during one-lung ventilation. This trial aims to explore the clinical application and efficacy of intubation in the lateral position under general anesthesia induction to reduce the incidence of DLT malposition in patients undergoing unilateral video-assisted thoracic surgery (VATS). METHODS: In this prospective, single-center, parallel group, randomized, controlled trial, we will recruit 108 patients, aged 18-80 years, scheduled for elective unilateral VATS with DLT intubation under general anesthesia, and they will be randomly assigned to two groups: a lateral DLT intubation group (group L) and a conventional supine DLT intubation group (group C). The left-sided DLT will be used to intubate in patients of both groups. The position of DLT will be confirmed and adjusted by using the fiberoptic bronchoscopy (FOB). The primary outcome is the incidence of DLT malposition observed via the FOB, and the secondary outcomes include the time of intubation, the frequency and duration of re-adjustments of DLT placement under FOB, whether to re-intubate, intraoperative vital signs, and postoperative recovery. DISCUSSION: Accurate DLT positioning is crucially important for thoracic surgery, but the incidence of DLT malposition is still high in the present clinical practice of thoracic anesthesia. This trial aims to investigate whether lateral DLT intubation can reduce the incidence of DLT malposition, with more stable intraoperative vital signs and less postoperative complications. TRIAL REGISTRATION: The study protocol was registered at Chinese Clinical Trial Registry ( http://www.chictr.org.cn ) with registration number: ChiCTR2200060794 on June 11, 2022.

Network-pharmacology-based research on protective effects and underlying mechanism of Shuxin decoction against myocardial ischemia/reperfusion injury with diabetes.

BACKGROUND: Patients with diabetes mellitus are at higher risk of myocardial ischemia/ reperfusion injury (MI/RI). Shuxin decoction (SXT) is a proven recipe modi-fication from the classic herbal formula "Wu-tou-chi-shi-zhi-wan" according to the traditional Chinese medicine theory. It has been successfully used to alleviate secondary MI/RI in patients with diabetes mellitus in the clinical setting. However, the underlying mechanism is still unclear. AIM: To further determine the mechanism of SXT in attenuating MI/RI associated with diabetes. METHODS: This paper presents an ensemble model combining network pharmacology and biology. The Traditional Chinese Medicine System Pharmacology Database was accessed to select key components and potential targets of the SXT. In parallel, therapeutic targets associated with MI/RI in patients with diabetes were screened from various databases including Gene Expression Omnibus, DisGeNet, Genecards, Drugbank, OMIM, and PharmGKB. The potential targets of SXT and the therapeutic targets related to MI/RI in patients with diabetes were intersected and subjected to bioinformatics analysis using the Database for Annotation, Visualization and Integrated Discovery. The major results of bioinformatics analysis were subsequently validated by animal experiments. RESULTS: According to the hypothesis derived from bioinformatics analysis, SXT could possibly ameliorate lipid metabolism disorders and exert anti-apoptotic effects in MI/RI associated with diabetes by reducing oxidized low density lipoprotein (LDL) and inhibiting the advanced glycation end products (AGE)-receptor for AGE (RAGE) signaling pathway. Subsequent animal experiments confirmed the hypothesis. The treatment with a dose of SXT (2.8 g/kg/d) resulted in a reduction in oxidized LDL, AGEs, and RAGE, and regulated the level of blood lipids. Besides, the expression of apoptosis-related proteins such as Bax and cleaved caspase 3 was down-regulated, whereas Bcl-2 expression was up-regulated. The findings indicated that SXT could inhibit myocardial apoptosis and improve cardiac function in MI/RI in diabetic rats. CONCLUSION: This study indicated the active components and underlying molecular therapeutic mechanisms of SXT in MI/RI with diabetes. Moreover, animal experiments verified that SXT could regulate the level of blood lipids, alleviate cardiomyocyte apoptosis, and improve cardiac function through the AGE-RAGE signaling pathway.

Effects of high temperature and high humidity stress on the negative feedback regulation of hippocampus on HPA axis in rats.

OBJECTIVE: To investigate the negative feedback regulation from rat hippocampus on hypothalamic-pituitary-adrenal (HPA) axis under high temperature and high humidity stress. METHODS: Thirty (30) SD male rats were randomly divided into three groups: control group, high temperature and high humidity group, drug intervention group. The rats in control group were kept in the environment with temperature of 24 ± 1°C and humidity of 50 ± 5%, without any stimulation. The rats in the other groups were exposed to high temperature and high humidity environment for 4 h each day, with temperature of 35±1 °C and humidity of 85±5%. The rats in drug intervention group were intragastrically administered with the glucocorticoid receptor antagonist mifepristone. The administration was continued for 3 weeks. After 3 weeks, the serum levels of corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were detected by ELISA.The protein and mRNA levels of corticosteroid receptors (MR), glucocorticoid receptors (GR) and inducible nitric oxide synthase (iNOS), transient receptor potential vanilloid 1 (TRPV1) and 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) in hippocampus were determined by immunohistochemistry and in situ hybridization, respectively. The apoptosis of hippocampal cells was examined with TUNEL apoptosis staining. RESULTS: After stimulation with high temperature and high humidity stress for 3 weeks, the serum levels of CRH, ACTH and CORT in the high temperature and high humidity group were significantly increased compared to that of control group; the levels of these indicators in drug intervention group were decreased compared to that of high temperature and high humidity group (P<0.05). In high temperature and high humidity group, the protein and mRNA levels of MR, GR, iNOS in hippocampus of rats were significantly increased compared with that of control group (p<0.05); and the levels of these indicators in drug intervention group were lower than that of high temperature and high humidity group (p<0.05). In addition, compared with the control group, the TRPV1 protein level in hippocampus of rats in high temperature and high humidity group was not significantly changed (p>0.05), while the TRPV1 mRNA level was significantly increased (p<0.05). Neither the protein nor mRNA levels of 11ß-HSD1 showed significant difference compared to control group (p>0.05). The apoptosis of hippocampus cells in the high temperature and high humidity group was significantly increased compared with that of control group (p<0.05); and it was lower in the drug intervention group than that of in high temperature and high humidity group while the result was not significant (p>0.05). CONCLUSION: High temperature and high humidity stress may up-regulate the local expression of iNOS in hippocampus and decrease the activity of glucocorticoids (GC) receptor, then the effective binding of GR-GC would be decreased and the negative feedback regulation of hippocampus on HPA axis would be inhibited. The glucocorticoid receptor antagonist can improve the negative feedback regulation of hippocampus on HPA axis in rat.

Progesterone suppresses the progression of colonic carcinoma by increasing the activity of the GADD45α/JNK/c­Jun signalling pathway.

Colorectal cancer (CRC) is the third most diagnosed cancer worldwide. Progesterone is associated with a decreased risk of CRC and leads to a favourable prognosis. However, the specific mechanism by which progesterone suppresses malignant progression remains to be elucidated. In the present study, the level of progesterone was first analysed in 77 patients with CRC, and immunohistochemistry was performed to detect the expression of progesterone receptor (PGR) in the paired specimens. The correlations between progesterone, PGR and CRC prognosis were assessed. A Cell Counting Kit­8 assay was then used to detect proliferation of the CRC cells. Flow cytometry was performed to estimate apoptosis and to evaluate the cycle of the CRC cells. A xenograft tumour model was established in nude mice to assess the role of progesterone in tumour growth. Finally, a PCR microarray was used to screen differentially expressed genes to further interpret the mechanism by which progesterone inhibits the malignant progression of CRC. It was found that low expression of progesterone and PGR were significantly associated with poor prognosis of CRC. In addition, progesterone suppressed CRC cell proliferation by arresting the cell cycle and inducing apoptosis in vitro. Moreover, the inhibitory role of progesterone in tumour growth was verified in vivo. Further investigation showed that the level of growth arrest and DNA damage­inducible protein α (GADD45α) was up­regulated by progesterone, and this was followed by the activation of the JNK pathway. Progesterone increased the activity of the JNK pathway via GADD45α to inhibit proliferation by arresting the cell cycle and inducing apoptosis, thereby suppressing the malignant progression of CRC. Therefore, it can be concluded that progesterone and PGR might act as inhibiting factors for poor prognosis of CRC.

Effects of rhBMP-2 gene transfection to periodontal ligament cells on osteogenesis.

The present study aims to investigate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the osteogenesis of periodontal ligament (PDL) cells. The expression vector of rhBMP-2 (pcDNA3.1-rhBMP-2) was established. PDL cells were obtained through the enzymatic digestion and tissue explant methods and verified by immunohistochemistry. Cells were classified into experimental (cells transfected with pcDNA3.1/rhBMP-2-EGFP), blank (cells with no transfection) and control group (cells transfected with empty plasmid). rhBMP-2 expression was assessed via Western blotting analysis. The mineralization ability, alkaline phosphatase (ALP) activity and level of related osteogenic biomarkers were detected to evaluate the osteogenic characteristics of PDL cells. The rhBMP-2 expression vector (pcDNA3.1-rhBMP-2) was successfully established. Primary PDL cells displayed a star or long, spindle shape. The cultured cells were long, spindle-shaped, had a plump cell body and homogeneous cytoplasm and the ellipse nucleus contained two or three nucleoli. Cells displayed a radial, sheaf-like or eddy-like arrangement after adherence growth. Immunohistochemical staining confirmed that cells originated from mesenchymal opposed to epithelium. The experimental group exhibited an enhanced mineralization ability, higher ALP activity and increased expression of rhBMP-2 and osteogenic biomarkers (Runx2, collagen type I and osteocalcin) than the blank and control group. The present study demonstrated that rhBMP-2 transfection enhances the osteogenesis of PDL cells and provides a possibility for the application of rhBMP-2 expression products in dental disease treatment.

IL-7 suppresses osteogenic differentiation of periodontal ligament stem cells through inactivation of mitogen-activated protein kinase pathway.

Periodontal ligament stem cells (PDLSCs) are tissue-specific mesenchymal stem cells (MSCs), having an important role in regenerative therapy for teeth loss. Interleukin-7 (IL-7) is a key cytokine produced by stromal cells including MSCs, and exhibits specific roles for B and T cell development and osteoblasts differentiation of multiple myeloma. However, the effect of IL-7 on osteogenic differentiation of PDLSCs remains unclear. Therefore, in the present study we determined whether IL-7 affects the proliferation and osteogenic differentiation of PDLSCs in vitro and explored the associated signaling pathways for IL-7-mediated cell differentiation. The results demonstrated that the isolated human PDLSCs possessed MSCs features, highly expressing CD90, CD44, CD105, CD29 and CD73, and almost did not expressed CD34, CD45, CD11b, CD14 and CD117. IL-7 could not significantly affect the proliferation of PDLSCs, but it decreased their osteogenic differentiation and inhibited alkaline phosphatase (ALP) activity. The results of quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting exhibited that the expression levels of Runx-2, SP7 and osteocalcin (OCN) were significantly reduced by IL-7. Further studies indicated that IL-7 did not significantly change JNK, ERK1/2 and p38 protein production, but markedly suppressed their phosphorylation levels. These data suggest that IL-7 inhibits the osteogenic differentiation of PDLSCs probably via inactivation of mitogen-activated protein kinase (MAPK) signaling pathway.

[Clinical observation on effect of modified huanglian wendan decoction in treating diabetic asymptomatic myocardial ischemia].

OBJECTIVE: To investigate the clinical efficacy of modified huanglian wendan decoction (MHWD) on diabetic asymptomatic myocardial ischemia. METHODS: Ninety patients were randomly divided into two groups. The control group (n=30) was given Xinkang tablet (XKT) at a dose of 20 mg, twice a day. The treated group (n=35) was given MHWD besides XKT as that given to the control group. The treatment course for both groups was 1 month. Indexes, including blood glucose, glycosylated hemoglobin, blood lipids, myocardial zymogram, hemorheologic parameters, urinary albumin, routine examination of blood and urine, function of liver and kidney, as well as 24h dynamic electrocardiogram and electrocardiogram exercise test were measured in the two groups before and after treatment. RESULTS: The total clinical effective rate in the treated group and the control group was 88.33% and 56.67% respectively (P < 0.05), showing significant difference between them. The frequency of ischemia attacking, paroxysmal cumulative time, motion related incidence were lower in the treated group after treatment than those in the control group. Besides, in the treated group after treatment, the level of blood lipids and hemorheologic parameters were significantly improved (P < 0.05 or P < 0.01), hematocrit was unchanged and triglyceride, red blood cell agglutination index and erythrocyte deformability index were obviously different to those in the control group (P < 0.05). While in the control group after treatment, except the improving of whole blood viscosity (P < 0.05), no significant change was found in the other indices. CONCLUSION: MHWD has effects in improving myocardial ischemia, bettering hemorheologic condition and reducing blood lipids.

Tormentic acid inhibits LPS-induced inflammatory response in human gingival fibroblasts via inhibition of TLR4-mediated NF-κB and MAPK signalling pathway.

OBJECTIVE: Periodontal disease is one of the most prevalent oral diseases, which is associated with inflammation of the tooth-supporting tissues. Tormentic acid (TA), a triterpene isolated from Rosa rugosa, has been reported to exert anti-inflammatory effects. The aim of this study was to investigate the anti-inflammatory effects of TA on lipopolysaccharide (LPS)-stimulated human gingival fibroblasts (HGFs). METHODS: The levels of inflammatory cytokines such as interleukin (IL)-6 and chemokines such as IL-8 were detected by enzyme-linked immunosorbent assay (ELISA). The expression of Toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), IκBα, p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) was determined by Western blotting. RESULTS: The results showed that Porphyromonas gingivalis LPS significantly upregulated the expression of IL-6 and IL-8. TA inhibited the LPS-induced production of IL-6 and IL-8 in a dose-dependent manner. Furthermore, TA inhibited LPS-induced TLR4 expression; NF-κB activation; IκBα degradation; and phosphorylation of ERK, JNK, and P38. CONCLUSION: TA inhibits the LPS-induced inflammatory response in HGFs by suppressing the TLR4-mediated NF-κB and mitogen-activated protein kinase (MAPK) signalling pathway.

Enhanced expression of stem cell markers and drug resistance in sphere-forming non-small cell lung cancer cells.

There is growing evidence suggesting that cancer stem cells (CSCs) are playing critical roles in tumor progression, metastasis and drug resistance. However, the role of CSCs in non-small cell lung cancer (NSCLC) remains elusive. In this study, we enriched for stem-like cells from tumor spheres derived from NSCLC cell line A549 cultured in serum-free medium. Our results showed that sphere-derived cells expressed various stem cell markers such as CD44, CD133, Sox2 and Oct4. Compared with the corresponding cells in monolayer cultures, sphere-derived cells showed marked morphologic changes and increased expression of the stem cell markers CD133. Furthermore, we found that sphere-derived cells exhibited increased proliferation, cell-cycle progression as well as drug-resistant properties as compared to A549 adherent cells. Consistently, expression of several drug resistance proteins, including lung resistance-related protein (LRP), glutathion-S-transferase-π (GST-π) and multidrug resistance proteins-1 (MRP1) were all significantly enhanced in sphere-derived cells. These results indicate the enrichment of CSCs in sphere cultures and support their role in regulating drug resistance in NSCLC.

MicroRNA-1 promotes apoptosis of hepatocarcinoma cells by targeting apoptosis inhibitor-5 (API-5).

Although microRNA-1 (miR-1) is a known liver cancer suppressor, the role of miR-1 in apoptosis of hepatoma cells has remained largely unknown. Our study shows that ectopic miR-1 overexpression induced apoptosis of liver hepatocellular carcinoma (HepG2) cells. Apoptosis inhibitor 5 (API-5) was found to be a potential regulator of miR-1 induced apoptosis, using a bioinformatics approach. Furthermore, an inverse relationship between miR-1 and API-5 expression was observed in human liver cancer tissues and adjacent normal liver tissues. Negative regulation of API-5 expression by miR-1 was demonstrated to promote apoptosis of HepG2 cells. Our study provides a novel regulatory mechanism of miR-1 in the apoptosis of hepatoma cells.

[Effect of high humidity environment on immune function in rats].

OBJECTIVE: To investigate effects of the variation of immune function in high humidity environment in different time, and lay a foundation for further study of the related mechanism. METHOD: Thirty SD rats were divided into 3 groups (n = 10): 20 day group, 40 day group in 90% relative humidity chamber and control group in normal relative humidity. Peripheral blood and spleens were collected to detect the levels of T lymphocyte subsets by Flow Cytometery. RESULTS: In peripheral blood of the 20 day group rats, the CD3+ %, CD4+ %, CD8+ % and CD4+/CD8+ were 52.91 +/- 6.27, 37.80 +/- 4.11, 14.85 +/- 3.73 and 2.72 +/- 0.82 separately. Expect CD3+ %, they all had significant differences (P < 0.05). In addition, the data of the 40 day group rats showed no diversity in statistics. In spleen, CD8+ % of the 20 day group rats was 6.23 +/- 2.87 with significant differences (P < 0.05) and IgG, IgA and IgM did not change a lot in blood serum of the high humidity groups except C3 of the 20 days group (P < 0.05). CONCLUSION: In high humidity environment, the immune function of the rats increased in the initial stage. As time went on, the immune function gradually went to normal level through the self adjustment.

Analysis of protein-protein interaction network and functional modules on primary osteoporosis.

BACKGROUND: Primary osteoporosis is an age-related disease, and the main cause of this disease is the failure of bone homeostasis. Previous studies have shown that primary osteoporosis is associated with gene mutations.To explore the functional modules of the PPI (protein-protein interaction) network of differentially expressed genes (DEGs), and the related pathways participating in primary osteoporosis. METHODS: The gene expression profile of primary osteoporosis GSE35956 was downloaded from the GEO (Gene Expression Omnibus) database and included five MSC (mesenchymal stem cell) specimens of normal osseous tissue and five MSC specimens of osteoporosis. The DEGs between the two types of MSC specimens were identified by the samr package in R language. In addition, the functions and pathways of DEGs were enriched. Then the DEGs were mapped to String to acquire PPI pairs and the PPI network was constructed with by these PPI pairs. Topological properties of the network were calculated by Network Analyzer, and modules in the network were screened by Cluster ONE software. Subsequently, the fronting five modules whose P-value was less than 1.0e-05 were identified and function analysis was conducted. RESULTS: A total of 797 genes were filtered as DEGs from these ten specimens of GSE35956 with 660 up-regulated genes and 137 down-regulated genes. Meanwhile, up-regulated DEGs were mainly enriched in functions and pathways related to cell cycle and DNA replication. Furthermore, there were 4,135 PPI pairs and 377 nodes in the PPI network. Four modules were enriched in different pathways, including cell cycle and DNA replication pathway in module 2. CONCLUSIONS: In this paper, we explored the genes and pathways involved in primary osteoporosis based on gene expression profiles, and the present findings have the potential to be used clinically for the future treatment of primary osteoporosis.

[Cognitive impairment in earthquake brain injury treated with comprehensive program of acupuncture and rehabilitation: a randomized controlled trial].

OBJECTIVE: To explore the comprehensive program of integrated Chinese and western medicine in the treatment of cognitive impairment in earthquake brain injury. METHODS: The multi-central randomized controlled trial was adopted. The qualified subjects were randomized into an acupuncture + rehabilitation group (38 cases) and a rehabilitation group (35 cases). In the acupuncture + rehabilitation group, acupuncture, hyperbaric oxygen (HBO) and cognitive rehabilitation training were combined as the comprehensive program of integrated Chinese and western medicine in the treatment. In the rehabilitation group, HBO and cognitive rehabilitation training were adopted. The efficacy and safety were assessed. RESULTS: (1) After treatment of 2 months, the intelligent state, cognitive function and activity of daily life of patients were improved in the both groups (all P < 0.01). (2) After treatment of 2 months, the score of MMSE and the score of activity of daily life were (24.11 +/- 4.08) and (75.45 +/- 13.95) in the acupuncture + rehabilitation group, which were more significant as compared with (17.05 +/- 43.84), (66.06 +/- 12.75) in the rehabilitation group, respectively (both P < 0.01). In 6-month follow-up visit after treatment, the cognitive function and activity of daily life were improved continuously in the acupuncture + rehabilitation group, which was more significant as compared with the rehabilitation group (P < 0.01, P < 0.05). CONCLUSION: The integrated Chinese and western medicine of acupuncture, HBO and cognitive rehabilitation training is safe and effective in the treatment of cognitive impairment in earthquake brain injury. The therapeutic effect is more advantageous as compared with the simple rehabilitation program of western medicine.

[Therapy of relapsed or refractory non-Hodgkin's lymphoma by antigen specific dendritic cells-activated lymphocytes].

This study was aimed to investigate the killing activity of cytokine-induced killer (CIK) cells after being incubated with autologous tumor cell lysate-pulsed dendritic cells (DC) and to evaluate the clinical efficacy and side effect of autologous tumor cell lysate-loaded DC in combination with CIK on relapsed or refractory non-Hodgkin's lymphoma (NHL). Peripheral blood mononuclear cells (PBMNC) were isolated from 9 patients with NHL, and cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) to produce DC. The DC were pulsed with autologous tumor cell lysate. T lymphocytes from PBMNC were cultured with interferon-gamma (IFN-gamma), IL-2, CD3-moAb, and IL-1alpha to prepare CIK. After receiving the immunotherapy of DC and CIK, immunologic and clinical responses were evaluated. The results showed that the AgNOR, CD3(+)CD8(+) and CD3(+)CD56(+) ratio were markedly improved after the immunotherapy (p < 0.01); IFN-gamma and IL-12 levels in supernatant of DC-CIK group were higher than that in CIK group (p < 0.01); Tumor size were significantly decreased after the immunotherapy (p < 0.05). Except transient fever and chill, no remarkable adverse event happened during or after the treatment. It is concluded that the autologous tumor cell lysate-pulsed DC in combination with CIK show ability to specifically kill the lymphoma cells, obviously increases the IS value of Ag-NOR in peripheral lymphocytes, secretes cytokines higher than CIK cells alone. This combination displays the short-term satisfied efficacy on NHL through inducing specific antitumor immunity, and can be used as an effective adjuvant measure for the routine therapy of NHL.