[Analysis of clinical research outcome indicators of traditional Chinese medicine in treatment of diabetic foot].

To analyze the outcome indicators from the randomized controlled trials(RCTs) on traditional Chinese medicine(TCM) treatment for diabetic foot, and to lay a foundation for the establishment of the core index set of the clinical trials on TCM treatment of diabetic foot. Computer retrieval of RCTs on TCM treatment of diabetic foot was performed in CNKI, Wanfang, SinoMed, PubMed, Cochrane Library, EMbase and Web of Science databases. Literature screening and data extraction were conducted independently by two researchers in strict accordance with inclusion and exclusion criteria. Any difference was resolved through discussion. A total of 72 RCTs involving 5 791 patients were included and 204 indicators were used. The number of indicators used in a single study was 2-22, with an average of 3 indicators used for each RCT. The indicators with top 16 frequency were clinical total effective rate, ankle brachial index(ABI), ulcer area, TCM syndrome integral, fibrinogen(FIB), fasting blood glucose(FBG), plasma viscosity(PV), c-reactive protein(CRP), saccharification blood of eggs(HbAlc), 2 h postprandial blood glucose(2 hPG), wound healing time, triglyce-rides(TC), TCM efficacy for syndromes, total cholesterol(TG), percutaneous oxygen partial pressure(TCPO2) and TCM symptom scores. The difference in selection of RCT indicators was large among TCM treatment methods for diabetic foot, and the combination of outcome indicators was arbitrary. The description on indexes was not standardized. Some non-laboratory examination indicators, some indicators not recommended in guidelines or not recognized in clinical practice, and some self-made indicators were not explained in detail. There was a lack of standardized evaluation criteria for indicators. The indicators had large time-point difference in measurement, and the time points were not distinguished in the measurement for diabetic foot patients with different degrees of severity. In addition, the patients with long course of treatment weren't timely measured. The characteristics of TCM or significant endpoint indicators were insufficient. It was urgent to establish the core index set of TCM in treating diabetic foot.

[Systematic evaluation on efficacy and safety of Gingko Ketone Ester Dropping Pills in treatment of angina pectoris and coronary heart disease].

To systemically evaluate the efficacy and safety of Gingko Ketone Ester Dropping Pills in treating angina pectoris and co-ronary heart disease. CNKI, Wanfang, SinoMed, PubMed, Cochrane Library and EMbase databases were retrieved on computer, and the randomized clinical trial(RCT) on Gingko Ketone Ester Dropping Pills in treating angina pectoris and coronary heart disease, which were published from the database establishment to December 31, 2019, were comprehensively collected. Literature screening, data extraction and quality evaluation were conducted independently by two researchers according to inclusion and exclusion criteria. Literature methodology quality evaluation was conducted with use of the Cochrane Handbook 5.3.0(bias risk assessment tool). Meta-analysis was performed with RevMan 5.3.0 software. A total of 10 RCTs were included. The results of the Meta-analysis showed that as compared with conventional Western medicine alone, the application of Gingko Ketone Ester Dropping Pills combined with conventional Western medicine treatment further improved the total effective rate and electrocardiogram effect(RR=1.43,95%CI[1.20,1.71],P<0.000 1). There were statistically significant differences in the number of angina attacks, the duration of angina and the amount of nitroglycerin used. In terms of safety indicators, four studies reported adverse reactions in the experimental group, including facial flu-shing, tachycardia, dizziness, dyspnea, nausea and other symptoms. Based on the existing findings, in the treatment of angina pectoris and coronary heart disease, Gingko Ketone Ester Dropping Pills combined with conventional Western medicine can improve the clinical total effective rate, electrocardiogram effect, number of angina attacks, duration of angina and the amount of nitroglycerin used. However, in the included studies, due to some methodological quality problems which would impact the reliability of literature results more high-quality randomized controlled trials are still needed for further verification.

[Differential analysis of different study types in clinical safety evaluation of Xuebijing Injection].

This study aimed to comprehensively analyze and compare the differences of different clinical study types currently published in the safety evaluation of Xuebijing Injection. Six databases, namely the Cochrane Library, PubMed, EMbase, CNKI, VIP and Wanfang database, were electronically retrieved to collect all types of studies on the safety of Xuebijing Injection, including randomized controlled trials, case-controlled studies, cohort studies, systematic reviews, and centralized monitoring studies of clinical safety(hospital), in order to comprehensively and objectively evaluate the safety of Xuebijing Injection, and analyze the differences of different research results. A total of 211 literatures were included, involving a total of 46 384 patients treated with Xuebijing Injection, and 423 adverse reactions(ADRs) occurred. They included 191 randomized controlled trials, 3 cohort studies, 15 systematic reviews, and 2 centralized monitoring studies of clinical safety(hospital), and the incidence of adverse reactions was 2.54%(common), 2.31%(common), 0.95%(occasionally), and 0.50%(occasionally). More than half of the 423 cases of ADRs occurred in skin and adnexal system(151 cases) and gastrointestinal system(65 cases), including such manifestations as rash, skin itching, nausea and vomiting, diarrhea. The degree of ADRs was mild. Randomized controlled trials showed that the incidence of ADR was the highest when Xuebijing Injection was used for malignant tumor and multiple organ failure. And the systematic evaluation showed that the incidence of ADR was the highest when Xuebijing Injection was used for spontaneous peritonitis of liver cirrhosis. In conclusion, different study types could lead to significant differences in the results of drug safety evaluation. Sample size, study type, and quality control are the main factors for biased results. Due to large sample size and high-quality, centralized monitoring studies become the better clinical safety evaluation model of drugs at present, and full life cycle management could more objectively reflect drug safety and guide clinical rational drug use.

[Systematic review of efficacy and safety of Compound Danshen Injection combined with Western medicine in treatment of vascular dementia].

To evaluate the efficacy and safety of Compound Danshen Injection combined with Western medicine in the treatment of vascular dementia. Databases of Cochrane Library, PubMed, EMbase, CNKI, SinoMed, VIP, Wanfang Data were electronically retrieved for collecting randomized controlled trial(RCT)about vascular dementia treated with Western medicine alone or combined with Compound Danshen Injection from the year of database establishment to January 2020. Two researchers independently screened out li-teratures, extracted data, and evaluated the risk of bias for inclusion in the study. Meta-analysis was conducted using RevMan 5.3 software. A total of 5 RCTs were included, involving 588 patients, with 299 in treatment group and 289 in control group. Meta-analysis results showed that compared with Western medicine alone, Compound Danshen Injection combined with Western medicine was better in the effective rate(RR=1.23,95%CI[1.14,1.33],P<0.000 01), MMSE score(MD=3.54,95%CI[3.01,4.06],P<0.000 01), ADL score(MD=11.49,95%CI[8.05,14.93],P<0.000 01), the level of CRP(MD=-0.72,95%CI[-1.25,-0.20],P=0.007) and the level of IL-6(MD=-7.64,95%CI[-9.65,-5.63],P<0.000 01). Adverse reactions mainly included rash and skin prick, which did not affect the treatment effect. Based on the findings, the combination of Compound Danshen Injection in the treatment of vascular dementia could improve the effective rates, relieve the mental state damage and improve the daily living ability, with mild adverse reactions and a low incidence. However, due to the low quality of the included literatures, high-quality and large-scale randomized controlled trials are needed for further verification.

Safety Evaluation and Experimental Study of a New Bionic Muscle Cable-Driven Lower Limb Rehabilitation Robot.

Safety is a significant evaluation index of rehabilitation medical devices and a significant precondition for practical application. However, the safety evaluation of cable-driven rehabilitation robots has not been reported, so this work aims to study the safety evaluation methods and evaluation index of cable-driven rehabilitation robots. A bionic muscle cable (BM cable) is proposed to construct a bionic muscle cable-driven lower limb rehabilitation robot (BM-CDLR). The working principle of the BM-CDLR is introduced. The safety performance factors are defined based on the mechanical analysis of the BM-CDLR. The structural safety evaluation index and the use safety evaluation index of the BM-CDLR are given by comprehensively considering the safety performance factors and a proposed speed influence function. The effect of the structural parameters of the elastic elements in the BM cable on the safety performance factors and safety of the BM-CDLR is analyzed and verified by numerical simulations and experimental studies. The results provide the basis for further study of the compliance control strategy and experiments of the human-machine interaction of the BM-CDLR.

[Research advancement: overview of system reviews of traditional Chinese medicine].

Currently, the quantity of clinic research, Meta-analysis and overview of traditional Chinese medicine(TCM) were advanced annually. The secondary researches can support to more evidential reference for clinic decision, policy design etc. Meanwhile, the need of expedite and valuable evidence was increasingly. This study was collected published overview of system review of TCM by CNKI, WanFang, VIP, SinoMed, PudMed, Cochrane Library and Ovid database. The characteristic data extraction were included: title, type of literature, author and nationality, published year, quantity of subject, quantity of original documents included, Chinese and English databases searched, type of disease, intervention, study result(positive/negative), adverse reaction, quality assessment tool, study limitation, level of evidence etc. Base these data above, to summarize the overview of system reviews of TCM by bibliometrics and overview analysis.

[Network Meta-analysis of Yiqi Huoxue Chinese patent medicine for coronary heart disease with angina pectoris].

To assess the clinical efficacy of Yiqi Huoxue Chinese patent medicine for coronary heart disease with angina pectoris by using network Meta-analysis method. The relative randomized controlled trials( RCTs) of Yiqi Huoxue Chinese patent medicine for coronary heart disease with angina pectoris were retrieved from China National Knowledge Infrastructure( CNKI),Wan Fang,VIP and Chinese Biomedical Literature Database( CBM) in July 2018. Two researchers independently completed the literature screening,data extraction and quality evaluation according to the pre-determined inclusion and exclusion criteria,and the results were cross-checked.The data were analyzed by Win Bugs,and STATA software was used for plotting. Finally,114 RCTs were included,involving 7 Yiqi Huoxue Chinese patent medicines and 11 775 patients. Network Meta-analysis showed that the total effective rate for improvement in AP symptoms had 7 direct comparisons and 21 indirect comparisons,8 of which were statistically significant. The ECG improvement had 7 direct comparisons and 21 indirect comparisons,7 of which were statistically significant. In terms of the total effective rate of improvement in AP symptoms,the order of efficacy was as follows: Shensong Yangxin Capsules > Shexiang Baoxin Pills > Qishen Yiqi Dropping Pills > Tongxinluo Capsules > Wenxin Granules > Qishen Capsules > Naoxintong Capsules. In terms of ECG improvement,the order of efficacy was as follows: Shexiang Baoxin Pills > Tongxinluo Capsules > Naoxintong Capsules > Qishen Yiqi Dropping Pills> Wenxin Granules > Shensong Yangxin Capsules > Qishen Capsules. The results showed that Shensong Yangxin Capsules and Shexiang Baoxin Pills had certain advantages in the treatment of coronary heart disease with angina pectoris. Due to the small sample size,more studies were required to further verify the evidences.

T2-weighted balanced steady-state free procession MRI evaluated for diagnosing placental adhesion disorder in late pregnancy.

OBJECTIVE: This study evaluated the imaging characteristics and accuracy of T2-weighted (T2W) balanced steady-state free procession (b-SSFP) magnetic resonance imaging, relative to b-SSFP or single-shot fast spin echo (SSFSE), for the diagnosis of placental adhesion disorder (PAD). METHODS: Fifty-one pregnant patients suspected of PAD were examined with T2W b-SSFP, b-SSFP and SSFSE. The image types were independently analysed for signs of PAD: abnormal placental bulge (APB), dark intraplacental bands (DIB), placental heterogeneity (PH) and placental protrusion into adjacent structures (PPAS). The sequences were compared for muscle-to-placenta signal ratio, signs of PAD and area under the receiver operating characteristic curve (AUC) for diagnostic accuracy of PAD. RESULTS: PAD was confirmed in 34 women. The muscle-to-placenta signal ratio was highest in the T2W b-SSFP. The diagnostic rates of APB in T2W b-SSFP were comparable to that of b-SSFP, but were significantly higher than that of SSFSE. The rates of PH in SSFE were comparable to that of b-SSFP, but both were significantly lower than that of T2W b-SSFP. The rates of DIB were significantly higher in T2W b-SSFP images compared with SSFSE. Rates of PPAS were comparable among three sequences. The AUCs of the T2W b-SSFP, b-SSFP and SSFSE were 0.966, 0.890 and 0.823, respectively. CONCLUSION: T2W b-SSFP has high diagnostic accuracy for PAD relative to SSFSE or b-SSFP, which may be due to its high SNR, T2-weighting and lack of blur. KEY POINTS: • Signal myometrium-to-placenta ratio was highest in the T2W b-SSFP images. • Diagnostic rate of APB in T2W b-SSFP was highest. • Diagnostic rate of DIB was higher in T2W b-SSFP than in SSFSE. • Diagnostic rate of PH in T2W b-SSFP was highest. • Maximum AUC for diagnostic accuracy of PAD was in T2W b-SSFP.

Molecular cloning, mRNA expression and alternative splicing of a ryanodine receptor gene from the citrus whitefly, Dialeurodes citri (Ashmead).

Insect ryanodine receptors are the main targets of diamide insecticides that have highly selective insecticidal activity but are less toxic to mammals. Therefore, these insecticides are ideal for pest control. Ryanodine receptors (RyRs) play a critical role in Ca2+ signaling in muscle and non-muscle cells. In this study, we cloned the complete cDNA (DcRyR) of the RyR from the citrus whitefly, Dialeurodes citri, a serious pest of citrus orchards in China. The open reading frame of RyR is 15,378bp long and encodes a protein with 5126 amino acids with a computed molecular weight of 579.523kDa. DcRyR shows a high amino acid sequence identity to RyRs from other insects (76%-95%) and low identity to those from nematodes and mammals (44%-52%). DcRyR shares many features of insect and vertebrate RyRs, including a MIR domain, two RIH domains, three SPRY domains, four copies of RyR repeat domain, RIH-associated domain at the N-terminus, two consensus calcium-binding EF-hands and six transmembrane domains at the C-terminus. The expression of DcRyR mRNA was the highest in the nymphs and lowest in eggs; DcRyR mRNA was 1.85-fold higher in the nymphs than in the eggs. Among the tissues, DcRyR mRNA expression was 4.18- and 4.02-fold higher in the adult head and thorax than in the abdomen. DcRyR had three alternative splice sites and the splice variants showed body part-specific expression and were developmentally regulated. These results may help investigate target-based resistance to diamide insecticides in D. citri.

Molecular Characterization, mRNA Expression and Alternative Splicing of Ryanodine Receptor Gene in the Brown Citrus Aphid, Toxoptera citricida (Kirkaldy).

Ryanodine receptors (RyRs) play a critical role in regulating the release of intracellular calcium, which enables them to be effectively targeted by the two novel classes of insecticides, phthalic acid diamides and anthranilic diamides. However, less information is available about this target site in insects, although the sequence and structure information of target molecules are essential for designing new control agents of high selectivity and efficiency, as well as low non-target toxicity. Here, we provided sufficient information about the coding sequence and molecular structures of RyR in T. citricida (TciRyR), an economically important pest. The full-length TciRyR cDNA was characterized with an open reading frame of 15,306 nucleotides, encoding 5101 amino acid residues. TciRyR was predicted to embrace all the hallmarks of ryanodine receptor, typically as the conserved C-terminal domain with consensus calcium-biding EF-hands (calcium-binding motif) and six transmembrane domains, as well as a large N-terminal domain. qPCR analysis revealed that the highest mRNA expression levels of TciRyR were observed in the adults, especially in the heads. Alternative splicing in TciRyR was evidenced by an alternatively spliced exon, resulting from intron retention, which was different from the case of RyR in Myzus persicae characterized with no alternative splicing events. Diagnostic PCR analysis indicated that the splicing of this exon was not only regulated in a body-specific manner but also in a stage-dependent manner. Taken together, these results provide useful information for new insecticide design and further insights into the molecular basis of insecticide action.

Design and analysis of a lower limb assistive exoskeleton robot.

BACKGROUND: In recent years, exoskeleton robot technology has developed rapidly. Exoskeleton robots that can be worn on a human body and provide additional strength, speed or other abilities. Exoskeleton robots have a wide range of applications, such as medical rehabilitation, logistics and disaster relief and other fields. OBJECTIVE: The study goal is to propose a lower limb assistive exoskeleton robot to provide extra power for wearers. METHODS: The mechanical structure of the exoskeleton robot was designed by using bionics principle to imitate human body shape, so as to satisfy the coordination of man-machine movement and the comfort of wearing. Then a gait prediction method based on neural network was designed. In addition, a control strategy according to iterative learning control was designed. RESULTS: The experiment results showed that the proposed exoskeleton robot can produce effective assistance and reduce the wearer's muscle force output. CONCLUSION: A lower limb assistive exoskeleton robot was introduced in this paper. The kinematics model and dynamic model of the exoskeleton robot were established. Tracking effects of joint angle displacement and velocity were analyzed to verify feasibility of the control strategy. The learning error of joint angle can be improved with increase of the number of iterations. The error of trajectory tracking is acceptable.

Mazabraud's syndrome in female patients: Two case reports.

BACKGROUND: Mazabraud's syndrome (MS) is a rare and slowly progressive benign disease characterized by the concurrent presence of fibrous dysplasia of bone and intramuscular myxoma, and is thought to be associated with mutations of the GNAS gene. To date, only about 100 cases of MS have been reported in the literature, but its standard treatment strategy remains unclear. CASE SUMMARY: We report two cases of MS in young women who underwent different treatments based on their symptoms and disease manifestations. The first patient, aged 37, received internal fixation and intravenous bisphosphonate for a pathological fracture of the right femoral neck, excision of a right vastus medialis myxoma was subsequently performed for pain control, and asymptomatic psoas myxomas were monitored without surgery. Genetic testing confirmed a GNAS gene mutation in this patient. The second patient, aged 24, underwent right vastus intermedius muscle myxoma resection, and conservative treatment for fibrous dysplasia of the ilium. These patients were followed-up for 17 months and 3 years, respectively, and are now in a stable condition. CONCLUSION: Various treatments have been selected for MS patients who suffer different symptoms. The main treatment for myxomas is surgical resection, while fibrous dysplasia is selectively treated if the patient experiences pathological fracture or severe pain. However, given the documented instances of malignant transformation of fibrous dysplasia in individuals with MS, close follow-up is necessary.

Plasma SIRT3 as a Biomarker of Severity and Prognosis After Acute Intracerebral Hemorrhage: A Prospective Cohort Study.

Objective: SIRT3 may act as a brain-protective factor. We measured the plasma SIRT3 levels of patients with intracerebral hemorrhage (ICH) and further determined the relationship between plasma SIRT3 and clinical outcome plus severity of ICH. Methods: In this prospective cohort study, we quantified plasma SIRT3 levels in 105 ICH patients and 72 healthy controls. Glasgow Coma Scale (GCS) score and hematoma volume were used to assess severity. Poor prognosis was defined as a Glasgow Outcome Scale (GOS) score of 1-3 at 90 days after ICH. Results: Plasma SIRT3 levels were markedly lower in patients than in controls (median, 10.19 versus 13.17 ng/mL; P<0.001). Among all patients, plasma SIRT3 levels were independently correlated with hematoma volume (beta, -0.098; 95% confidence interval, -0.158--0.039; t, -3.282; P=0.001) and GCS score (beta, 0.465; 95% confidence interval, 0.107-0.823; t, 2.576; P=0.011). A total of 46 cases had a poor prognosis at post-stroke 90 days. The plasma levels of SIRT3 significantly decreased in patients with a poor prognosis, compared with those with a good prognosis (median, 6.1 versus 11.2 ng/mL; P<0.001). Plasma SIRT3 was an independent predictor for 90-day poor prognosis of patients (odds ratio, 0.837; 95% confidence interval, 0.708-0.990; P=0.038). Plasma SIRT3 levels distinguished the development of poor prognosis with area under receiver operating characteristic curve at 0.801 (95% confidence interval, 0.711-0.872) and plasma SIRT3 levels ≤7.38 ng/mL predicted poor prognosis with 63.04% sensitivity and 93.22% specificity. Conclusion: Declined plasma SIRT3 levels are highly associated with hemorrhagic severity and poor 90-day outcome, thus suggesting that plasma SIRT3 may serve as a potential prognostic biomarker for ICH.

[Serum IL-18 levels in mice with collagen-induced arthritis treated by recombinant adenovirus containing mIL-18BP and mIL-4 fusion gene].

OBJECTIVE: To investigate serum IL-18 levels in mice with collagen-induced arthritis treated by recombinant adenoviral vector containing mIL-18BP and mIL-4 fusion gene (AdmIL-18BP/mIL-4). METHODS: Arthritis was induced by injection of collagen in male DBA-1/BOM mice. Mice with collagen-induced arthritis (CIA) were intra-articularly injected with 10(7)pfu/6µL of AdmIL-18BP/mIL-4; and in mice of control groups AdLacZ or PBS were used. The animals were sacrificed at week 1, 2 and 4 after treatment. Serum IL-18 levels were determined by ELISA at the different time points. RESULT: The mean serum levels of IL-18 at weeks 1, 2, and 4 after injection of AdmIL-18BP/mIL-4 were (36.5±5.4)ng/L, (32.5 ± 3.2) ng/L and (28.7 ±2.9)ng/L, respectively, which were significantly lower than those at the same time point of AdLacZ group [(66.2 ±5.1)ng/L, (69.2 ±4.2)ng/L and (77.7 ±3.9)ng/L] and PBS group [(67.3 ±7.1)ng/L, (71.9 ±1.8)ng/L and (78.7±4.1)ng/L] (P<0.01 at all time points). In the therapy group, there were no significant differences in the mean serum concentrations of IL-18 at all time points. CONCLUSION: The serum IL-18 levels in CIA mice are down-regulated by treatment of recombinant adenovirus containing mIL-18BP and mIL-4 fuse gene, which might be a promising therapeutic strategy for rheumatoid arthritis.

Carotid wall imaging with 3D_T2_FFE: sequence parameter optimization and comparison with 3D_T2_SPACE.

Similar to sampling perfection with application-optimized contrast using different flip angle evolutions (SPACE), T2-weighted fast field echo (FFE) also has a black blood effect and a high imaging efficiency. The purpose of this study was to optimize 3D_T2_FFE and compare it with 3D_T2_SPACE for carotid imaging. The scanning parameter of 3D_T2_FFE was optimized for the imaging of the carotid wall. Twenty healthy volunteers and 10 patients with carotid plaque underwent cervical 3D_T2_FFE and 3D_T2_SPACE examinations. The signal-to-noise ratios of the carotid wall (SNRwall) and lumen (SNRlumen), and the contrast-to-noise ratios between the wall and lumen (CNRwall_lumen) were compared. The incidence of the residual flow signal at the carotid bifurcation and the grades of flow voids in the cerebellopontine angle region in the two sequences were also compared. The reproducibility of the two sequences was tested. No significant difference was observed between the two sequences in terms of the SNRwall of healthy individuals and patients (P = 0.132 and 0.102, respectively). The SNRlumen in the 3D_T2_FFE images was lower than that in the 3D_T2_SPACE images. No significant difference was observed between the two sequences in terms of the CNRwall-lumen. The incidence of the residual flow signal at the carotid bifurcation in 3D_T2_FFE was significantly lower than that in 3D_T2_SPACE. The grades of flow suppression in the cerebellopontine angle region in 3D_T2_SPACE was lower than that in 3D_T2_FFE. Both sequences showed excellent inter-and intra-observer reproducibility. Compared to 3D_T2_SPACE, 3D_T2_FFE showed stronger flow suppression while maintaining good imaging quality, which can be used as an alternative tool for carotid imaging.

Serum glucose and potassium ratio as a predictive factor for prognosis of acute intracerebral hemorrhage.

OBJECTIVE: The serum glucose/potassium ratio (GPR) is a potential prognostic predictor for acute brain injury-related diseases. We calculated the serum GPR in patients with acute intracerebral hemorrhage (ICH) and explored its prognostic value for long-term prognoses and ICH severity. METHODS: This retrospective cohort study consecutively included 92 patients with ICH and 92 healthy controls. The National Institutes of Health Stroke Scale (NIHSS) score, Glasgow coma scale (GCS) score, and hematoma volume were used to assess severity. A modified Rankin Scale score > 2 at 90 days post-stroke was defined as a poor outcome. RESULTS: The serum GPR was significantly higher in patients than controls. The serum GPR was weakly correlated with the NIHSS score, GCS score, and hematoma volume. The serum GPR, GCS score, and hematoma volume were independently associated with poor outcomes. In the receiver operating characteristic curve analysis, the serum GPR remarkably discriminated patients at risk of poor outcomes at 90 days. The serum GPR significantly improved the prognostic predictive capability of hematoma volume and tended to increase that of the GCS score. CONCLUSION: Serum GPR is an easily obtained clinical variable for predicting clinical outcomes after ICH.

Serum Hypoxia-Inducible Factor 1alpha Levels Correlate with Outcomes After Intracerebral Hemorrhage.

BACKGROUND: Serum hypoxia-inducible factor 1alpha (HIF-1α) is a key regulator in hypoxic and ischemic brain injury. We determined the relationship between serum HIF-1α levels and long-term prognosis plus severity of intracerebral hemorrhage (ICH). METHODS: A total of 97 ICH cases and 97 healthy controls were enrolled. Glasgow Coma Scale (GCS) score and hematoma volume were used to assess hemorrhagic severity. Glasgow Outcome Scale (GOS) score of 1-3 at post-stroke 90 days was defined as a poor outcome. RESULTS: Serum HIF-1α levels of ICH patients were significantly higher than those of healthy controls (median, 218.8 vs 105.4 pg/mL; P<0.001) and were substantially correlated with GCS score (r=-0.485, P<0.001), hematoma volume (r=0.357, P<0.001) and GOS score (r=-0.436, P<0.001). Serum HIF-1α levels >239.4 pg/mL discriminated patients at risk of 90-day poor outcome with sensitivity of 65.9% and specificity of 79.3% (area under the receiver operating characteristic curve, 0.725; 95% confidence interval, 0.625-0.811; P<0.001). Moreover, serum HIF-1α levels >239.4 pg/mL were independently associated with a poor 90-day outcome (odds ratio, 5.133; 95% confidence interval, 1.117-23.593; P=0.036). CONCLUSION: Serum HIF-1α, in close correlation with hemorrhagic severity and poor 90-day outcome, may serve as a potential prognostic biomarker for ICH.

Inflammation induced by lipopolysaccharide advanced androgen receptor expression and epithelial-mesenchymal transition progress in prostatitis and prostate cancer.

BACKGROUND: To explore the mechanism of prostatic inflammation on prostate cancer (PCa) by comparing the changes of prostate epithelial cells and PCa cells in an inflammatory environment. METHODS: First, immunohistochemistry (IHC) was used to compare the level of expression of TNF-α, IL-1ß, IL-6, and TGF-ß between benign prostatic hyperplasia (BPH), prostatitis, and PCa. Then primary prostate epithelial cells were sampled from patients who were suspected of PCa and had histological prostatitis (HP) confirmed by pathological biopsy. Lipopolysaccharide (LPS) or BAY11-7082 were used to investigate the change of androgen receptor (AR) and AR-mediated transcription, epithelial-mesenchymal transition (EMT) in primary prostate epithelial cells, and lymph node carcinoma of the prostate (LNCap) cells. RESULTS: TNF-α, IL-1ß, IL-6, and TGF-ß were significantly increased in HP and PCa compared with those in BPH patients. The proliferation of primary prostate epithelial cells and LNCap cells got the inflection point at LPS 10 µg/mL. In an inflammatory environment with 10 µg/mL LPS, both primary prostate epithelial cell and LNCap cell viability increased, and AR, AR-mediated transcription, and EMT processes were significantly increased. Inhibitors of NF-κB with 10 nM BAY11-7082 decreased AR, AR-mediated transcription, and EMT processes. CONCLUSIONS: NF-κB regulates AR expression and EMT in prostatitis and PCa, and NF-κB inhibitors may have potential therapeutic value.

Neuroprotective effects of vitamin D and 17ß-estradiol against ovariectomy-induced neuroinflammation and depressive-like state: Role of the AMPK/NF-κB pathway.

Estrogen replacement therapy (ERT) has been proven to relieve menopausal-related mental disorders including depression in postmenopausal women. However, the unsafety of ERT hinders its clinical use. In this study, we would evaluate whether vitamin D (VD), a hormone with optimal safety profile, could relieve the depressive-like symptom in ovariectomized (OVX) rats. Furthermore, we would determine whether vitamin D and 17ß-estradiol (E2) exert neurological function through their immunomodulatory effect in OVX rats. Middle-aged female SD rats were randomly divided into four groups, namely, control (SHAM), OVX, OVX + VD, and OVX + E2. Vitamin D (calcitriol, 100 ng/kg) and 17ß-estradiol (30 µg/kg) had been daily gavaged in the OVX + VD and OVX + E2 group, respectively. After 10-week administration, vitamin D and 17ß-estradiol both showed anti-depressive-like activity in the OVX rats. Using the method of immunofluorescent staining and western blot, vitamin D and 17ß-estradiol were demonstrated to upregulate each other's receptors, including VDR, ERα, and ERß in the hippocampus of OVX rats. Additionally, the upregulation of VDR, calbindin-D28k, and calbindin-D9k suggested that the vitamin D signaling system was amplified by vitamin D and 17ß-estradiol. Vitamin D and 17ß-estradiol showed neuroprotective effects by decreasing OVX-induced apoptosis and neuronal damage, regulating the AMPK/NF-κB signaling pathway, and reducing the proinflammatory cytokines (IL-1ß, IL-6, and TNFα), as well as iNOS and COX-2 in the hippocampus of OVX rats. Collectively, the present study demonstrated that vitamin D and 17ß-estradiol could upregulate each other's receptors and regulate the AMPK/NF-κB pathway to relieve the OVX-induced depressive-like state. The results could stimulate translational research towards the vitamin D potential for prevention or treatment of menopause-related depression.

Corpus cavernosum smooth muscle cell dysfunction and phenotype transformation are related to erectile dysfunction in prostatitis rats with chronic prostatitis/chronic pelvic pain syndrome.

BACKGROUND: The relationship between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED) has been shown in many studies. However, the specific mechanism remains unclear. This study was to investigate the corpus cavernosum smooth muscle cell function and phenotype transformation in Experimental autoimmune prostatitis (EAP) rats. METHODS: EAP was induced in rats by using prostate protein supplemented with immuneadjuvant extraction, and the max-ICP and MAP were measured. IHC and Masson staining were done to assess inflammatory infiltration and collagen deposition in the corpus cavernosum, respectively. Subsequently, normal rat and EAP rat CCSMCs were purified by tissue block implantation and differential adherence method. The oxidative stress, smooth muscle phenotype transformation, cell cycle and intracellular calcium ion transport were also evaluated. RESULTS: The ratio of max ICP/MAP in EAP rats significantly reduced, and the TNF-α content and collagen deposition in the corpus cavernosum markedly increased as compared to healthy rats. High-purity rat CCSMCs were obtained. Oxidative stress was evident and the cGMP content decreased in the EAP rat CCSMCs. The expression of Cav1.2, IP3R1 and RyR2 increased, but the SERCA2 expression decreased in EAP rat CCSMCs, which was accompanied by increased intracellular calcium. Increased expression of OPN, collagen and KCa3.1, decreased Calponin expression and increased proportion of cells in the S phase were also observed in the EAP rat CCSMCs. CONCLUSION: CP causes oxidative stress and imbalance of intracellular calcium in CCSMCs and promotes CCSMCs transformation from contractile to synthetic state, which may be involved in the pathogenesis of ED.