Ameliorative effect of resveratrol on acute ocular hypertension induced retinal injury through the SIRT1/NF-κB pathway.

Glaucoma is a kind of neurodegenerative disorder characterized by irreversible loss of retinal ganglion cells (RGCs) and permanent visual impairment. It is reported that resveratrol (RES) is a promising drug for neurodegenerative diseases. However, the detailed molecular mechanisms underlying its protective potential have not yet been fully elucidated. The present study sought to investigate whether resveratrol could protect RGCs and retinal function triggered by acute ocular hypertension injury through the SIRT1/NF-κB pathway. An experimental glaucoma model was generated in C57BL/6J mice. Resveratrol was intraperitoneally injected for 5 days. Sirtinol was injected intravitreally on the day of retinal AOH injury. RGC survival was determined using immunostaining. TUNEL staining was conducted to evaluate retinal cell apoptosis. ERG was used to evaluate visual function. The proteins Brn3a, SIRT1, NF-κB, IL-6, Bax, Bcl2, and Cleaved Caspase3 were determined using western blot. The expression and localisation of SIRT1 and NF-κB in the retina were detected by immunofluorescence. Our data indicated that resveratrol treatment significantly increased Brn3a-labelled RGCs and reduced RGC apoptosis caused by AOH injury. Resveratrol administration also remarkably decreased NF-κB, IL-6, Bax, and Cleaved Caspase3 proteins and increased SIRT1 and Bcl2 proteins. Furthermore, resveratrol treatment obviously inhibited the reduction in ERG caused by AOH injury. Importantly, simultaneous administration of resveratrol and sirtinol abrogated the protective effect of resveratrol, decreased NF-κB protein expression, and increased SIRT1 protein levels. These results suggest that resveratrol administration significantly mitigates retinal AOH-induced RGCs loss and retinal dysfunction, and that this neuroprotective effect is partially regulated through the SIRT1/NF-κB pathway.

[Correlation between cervical curvature and cervical disc bulging in young patients with neck pain].

OBJECTIVE: To explore the correlation between the curvature of the cervical spine and the degree of cervical disc bulging in young patients with cervical pain. METHODS: The clinical data of 539 young patients with neck pain from January 2015 to December 2018 were retrospectively analyzed. There were 251 males and 288 females, aged 18 to 40 (32.2±6.3) years old. The cervical curvature and cervical disc bulging were measured by cervical X-ray and MRI. According to cervical curvature, the patients were divided into 175 cases of cervical lordosis group (cervical curvature > 7 mm), 163 cases of cervical erection group (0

Endoplasmic reticulum stress mediates cortical neuron apoptosis after experimental subarachnoid hemorrhage in rats.

OBJECTIVE: Neuronal apoptosis plays an important pathological process in early brain injury (EBI) after subarachnoid hemorrhage (SAH). This pathological process leads to a poor neurological prognosis for patients. This study aimed to investigate whether endoplasmic reticulum (ER) stress mediates cortical neuron apoptosis in EBI after SAH. METHODS: Eighty-four male Sprague-Dawley rats were randomly assigned to different groups as follows: the control and the 3, 6, 12, 24, 48, and 72 h groups after SAH. The SAH model was established by injecting 0.3 mL of nonheparinized blood into the prechiasmatic cistern. Hematoxylin-eosin staining, Garcia scoring, Western blotting, transmission electron microscopy, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were performed. RESULTS: SAH reduced the neurological scores and reached a trough at 24 h after the SAH. The GRP78 expression was significantly upregulated at 6 h after the SAH, peaked at 24 h after the SAH, and then decreased. By comparison, the CHOP, caspase-12, ASK1, and p-c-Jun N-terminal kinase expressions were significantly upregulated at 12 h after the SAH and peaked at 24 h after the SAH. The most serious swelling of the rough ER was observed at 24 h after the SAH and remained notably swollen at 72 h after the SAH. The number of TUNEL-positive cells substantially increased significantly at 12 h after the SAH, and the neuronal apoptosis decreased ratio after reaching a peak at 24 h after the SAH. The apoptosis ratio at 72 h after the SAH was still significantly different from the ratio in the control group. CONCLUSION: Our study clearly demonstrated that ER stress mediates cortical neuron apoptosis after experimental subarachnoid hemorrhage in rats.

Dietary and lifestyle factors for primary prevention of nephrolithiasis: a systematic review and meta-analysis.

BACKGROUND: Dietary and lifestyle factors may play an important role in the increasing prevalence of nephrolithiasis. We aimed to review and quantify the associations between lifestyle factors and incident nephrolithiasis and suggest lifestyle changes for the primary prevention of nephrolithiasis. METHODS: PubMed, EMBASE, and Cochrane Library were searched up to May 2019, for observational studies and randomized controlled trials (RCTs) that assessed modifiable lifestyle factors and risk of nephrolithiasis in adults. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were computed using a random effects model. The I2 statistic was employed to evaluate heterogeneity. Subgroup analysis, sensitivity analysis and meta-regression were also conducted whenever possible. RESULTS: Fifty relevant articles with 1,322,133 participants and 21,030 cases in total were identified. Prominent risk factors for incident stones were body mass index (1.39,1.27-1.52), dietary sodium (1.38, 1.21-1.56), fructose, meat, animal protein, and soda. In contrast, protective factors included fluid intake (0.55, 0.51-0.60), a Dietary Approaches to Stop Hypertension (DASH) style diet (0.69, 0.64-0.75), alcohol (0.69, 0.56-0.85), water, coffee, tea, vegetables, fruits, dietary fiber, dietary calcium (0.83, 0.76-0.90), and potassium. Vitamin D (1.22, 1.01-1.49) and calcium (1.16, 1.00-1.35) supplementation alone increased the risk of stones in meta-analyses of observational studies, but not in RCTs, where the cosupplementation conferred significant risk. CONCLUSIONS: Several modifiable factors, notably fluid intake, dietary patterns, and obesity, were significantly associated with nephrolithiasis. Long-term RCTs are required to investigate the cost-effectiveness of dietary patterns for stone prevention. The independent and combined effects of vitamin D and calcium supplementation on nephrolithiasis need further elucidation.

Associations between nephrolithiasis and diabetes mellitus, hypertension and gallstones: A meta-analysis of cohort studies.

AIM: To review and clarify the strengths and directions of associations between nephrolithiasis and hypertension (HTN), diabetes mellitus (DM) and gallstones (GS) given the inconsistent results reported in cohort studies. METHODS: Relevant literature was searched in PubMed and EMBASE from inception to July 2019, for cohort studies that examined the relationships between kidney stones and these three diseases among adults. Pooled relative risks (RRs) were calculated by maximally adjusted risk estimates using a random effect model. Subgroup analysis, meta-regression and sensitivity analysis were conducted whenever appropriate. RESULTS: Of 3537 papers, 21 articles with each including 1 to 3 cohorts were identified. In this meta-analysis, nephrolithiasis was reciprocally linked to HTN, DM and GS. Kidney stones were significantly associated with 31%, 33% and 46% higher risks of incident HTN, DM and GS whereas GS was associated with a significantly higher risk of nephrolithiasis (RR: 1.49; 95% CI, 1.28-1.73), followed by HTN (RR: 1.30; 95% CI, 1.11-1.52) and DM (RR: 1.18; 95% CI, 1.07-1.29). Also, females with DM (RR: 1.29; 95% CI, 1.08-1.55) were more likely to develop kidney stones than diabetic male patients (RR: 0.91; 95% CI, 0.75-1.10). CONCLUSION: Although additional studies are needed to confirm these findings and elucidate the mechanisms, this study revealed possible bidirectional associations between nephrolithiasis and HTN, diabetes and GS, which reinforced the notion of nephrolithiasis as a systemic disease that requires comprehensive investigations.

Bladder cancer survival nomogram: Development and validation of a prediction tool, using the SEER and TCGA databases.

Bladder cancer (BC) is a common malignancy associated with high morbidity and mortality, however, accurate and convenient risk assessment tools applicable to BC patients are currently lacking. Previous studies using nomograms to evaluate bladder cancer (BC) survival have been based on small samples. Using a large dataset, this study aimed to construct more precise clinical nomograms to effectively predict bladder cancer survival.Data on patients with pathologically-confirmed bladder cancer were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Additional BC patient data for an external validation cohort were extracted from the Cancer Genome Atlas (TCGA) database. Clinical parameters that constituted potential risk factors were reviewed and analyzed using univariate and multivariate Cox proportional hazards regression. A nomogram was constructed with parameters that significantly correlated with the overall survival (OS). Prognostic performance of a nomogram was assessed using the concordance index (c-index), area under the receiver operating characteristic curve (AUC), and a calibration curve. The model was then tested with data from an internal and external validation cohort. Patients' survival was analyzed and compared with the Kaplan-Meier (KM) method.Multivariate Cox regression showed that age, sex, race, stage_T1, stage_T2a, stage_T2b, stage_T3a, stage_Ta, stage_Tis, stage_N, stage_M were independent predictors of BC survival. A nomogram was constructed based on these factors. The c-index of the nomogram was 0.7916 (95% confidence interval CI, 0.79-0.80). The calibration curve showed excellent agreement between the predicted and observed values. The c-index for the internal validation cohort was 0.7917 (95% CI 0.79-0.80), which was higher than for the training cohort, suggesting robustness of the model. For the training cohort, the AUC for the 3- and the 5-year survival was 0.82 and 0.813, respectively. The c-index for the TNM-based model was superior to that for the AJCC-TNM classification.The models presented in this study might be suitable for clinical use, supporting clinicians in their individualized assessment of expected survival in BC patients. They might also be used as a layered tool for clinical research.

Bladder preservation approach versus radical cystectomy for high-grade non-muscle-invasive bladder cancer: a meta-analysis of cohort studies.

BACKGROUND: High-grade non-muscle-invasive bladder cancer is superficial; nonetheless, it is an aggressive cancer. Proper management strategy selection following transurethral resection between bladder preservation (BP) and radical cystectomy (RC) could result in delayed or excessive treatment. Hence, selecting the optimal treatment modality remains controversial to date. METHODS: We searched MEDLINE, The Cochrane Library, EMBASE, China National Knowledge Infrastructure, and Wanfang database through 12 April 2018. Quality and publication bias were assessed using the Newcastle-Ottawa Scale and Begg's/Egger's test. We collected 2-year, 5-year, 10-year, and 15-year survival rate and hazard ratio (HR) for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). Using the Review Manager 5.2 software, we used the odds ratio (OR) of specific years and HR for meta-analysis. Subgroup analysis was performed by the original tumor state, radical cystectomy timing, bladder preservation modality, and age. RESULTS: In total, 11 cohorts with 1735 patients were selected for the meta-analysis. All OR of OS supported BP as a better treatment option; however, all OR of PFS had no significant differences. As for CSS, only the 15-year OR reflected a statistical significance preferring RC. Subgroup analysis showed that BP is more appropriate for patients older than 65 and G3 tumor. Limited data demonstrated that late RC (> 3 months) is more effective compared to early RC (< 3 months) and intravesical Bacillus Calmette-Guerin was not statistically different from that of RC. The mixed BP modalities were significantly better compared to RC in OS and worse in CSS, with both having a very low evidence strength. CONCLUSIONS: BP is a superior treatment modality compare to RC, especially for older patients and T1G3 or lower grade tumors. However, the superior BP modality was unclear. Conversely, RC could be a better option for younger patients. More specifically, late RC may be more beneficial but had a very-low-level of evidence. Quality of life should be considered equal to survival outcome; hence, post-treatment follow-up needs to be performed. Prospective randomized studies should be performed to overcome the limitations of this meta-analysis study. REGISTRATION: Registration ID is CRD42018093491 .

Phase II study on dose escalating schedule of paclitaxel concurrent with radiotherapy in treating patients with locally advanced non-small cell lung cancer.

OBJECTIVE: To evaluate clinical efficacy of a dose escalating schedule of paclitaxel concurrent with radiotherapy in treating patients with locally advanced non-small cell lung (NSCLC). METHODS: Patients with locally advanced NSCLC were treated with conventional fractionated radiotherapy or three dimensional conformal radiotherapy (3 DCRT), concurrently with a dose escalating schedule of paclitaxel. All patients were divided into three groups, A with paclitaxel 30 mg/m2, B with paclitaxel 60 mg/m2 and C with paclitaxel 90 mg/m2. Paclitaxel was repeated every week for a total of 4 or 6 weeks. RESULTS: Among 109 patients, response rates were 68.8%, 71.1% and 71.8% (p>0.05) for group A (n=32), B (n=38), and C (n=39) respectively. Accordingly, disease control rates were 81.3%, 81.6% and 82.1% (p>0.05). Progression-free survival time was 8.0 ± 5.0 months, 11.6 ± 6.1 months, and 14.8 ± 7.9 months (p<0.05), respectively. Overall survival time was 15. 4 ± 7.6 months, 18.2 ± 8.0 months, and 22.0 ± 7.6 months (p<0.05), one-year survival rates were 62.5%, 73.1% and 90.0% (p>0.05) and two-year survival rates were 31.3%, 38.5% and 50.0% (p<0.05) . Main side-effects were bone marrow suppression, radiation related esophagitis and gastrointestinal reaction. CONCLUSION: In treating patients with NSCLC, concurrent chemoradiotherapy with paclitaxel improves early response compared with conventional fractionated radiotherapy or 3 DCRT. The survival rate was improved with the addition of paclitaxel, but there was an increase in adverse reactions when the dose of paclitaxel was increased.

Biobutanol production in a Clostridium acetobutylicum biofilm reactor integrated with simultaneous product recovery by adsorption.

BACKGROUND: Clostridium acetobutylicum can propagate on fibrous matrices and form biofilms that have improved butanol tolerance and a high fermentation rate and can be repeatedly used. Previously, a novel macroporous resin, KA-I, was synthesized in our laboratory and was demonstrated to be a good adsorbent with high selectivity and capacity for butanol recovery from a model solution. Based on these results, we aimed to develop a process integrating a biofilm reactor with simultaneous product recovery using the KA-I resin to maximize the production efficiency of biobutanol. RESULTS: KA-I showed great affinity for butanol and butyrate and could selectively enhance acetoin production at the expense of acetone during the fermentation. The biofilm reactor exhibited high productivity with considerably low broth turbidity during repeated batch fermentations. By maintaining the butanol level above 6.5 g/L in the biofilm reactor, butyrate adsorption by the KA-I resin was effectively reduced. Co-adsorption of acetone by the resin improved the fermentation performance. By redox modulation with methyl viologen (MV), the butanol-acetone ratio and the total product yield increased. An equivalent solvent titer of 96.5 to 130.7 g/L was achieved with a productivity of 1.0 to 1.5 g · L-1 · h-1. The solvent concentration and productivity increased by 4 to 6-fold and 3 to 5-fold, respectively, compared to traditional batch fermentation using planktonic culture. CONCLUSIONS: Compared to the conventional process, the integrated process dramatically improved the productivity and reduced the energy consumption as well as water usage in biobutanol production. While genetic engineering focuses on strain improvement to enhance butanol production, process development can fully exploit the productivity of a strain and maximize the production efficiency.

rac-Methyl 2-(2-formyl-4-nitro-phen-oxy)hexa-noate.

In the racemic title compound, C(14)H(17)NO(6), the plane of the ester group of the methyl hexa-noate side chain makes a dihedral angle of 80.0 (2)° with the benzene ring, while the nitro group is approximately coplanar with the benzene ring [dihedral angle = 10.3 (2)°]. In the crystal, mol-ecules form weak aromatic C-H⋯O(nitro) hydrogen-bonding inter-actions, giving inversion dimers [graph set R(2) (2)(8)].

2-(Hy-droxy-meth-yl)pyridin-3-ol.

In the crystal structure of the title compound, C(6)H(7)NO(2), the mol-ecules are are linked by inter-molecular O-H⋯N and O-H⋯O hydrogen bonds; π-π stacking is observed between parallel pyridine rings of adjacent mol-ecules [centroid-to-centroid distance = 3.7649 (12) Å].

2-[(4,6-Dimeth-oxy-pyrimidin-2-yl)-oxy]benzaldehyde.

In the title compound, C(13)H(12)N(2)O(4), the dihedral angle between the benzene and pyrimidine rings is 55.57 (13)°. The carbonyl group and the two methoxyl groups are approximately coplanar with the benzene ring and pyrimidine ring; the C-C-C-O, C-O-C-N and C-O-C-C torsion angles being -6.1 (5), -4.8 (4) and 179.9 (3)°, respectively. In the crystal, mol-ecules are linked via C-H⋯O inter-actions, forming chains propagating along [110].

Comparative study on transcatheter arterial chemoembolization, portal vein embolization and high intensity focused ultrasound sequential therapy for patients.

OBJECTIVE: To investigate the safety and efficacy of transcatheter arterial chemoembolization (TACE), combined with portal vein embolization (PVE), and high intensity focused ultrasound (HIFU) sequential therapy in treating patients with hepatocellular carcinoma (HCC). METHODS: Patients with inoperative HCC were treated by two methods: in the study group with TACE first, then PVE a week later, and then TACE+PVE every two months as a cycle, after 2~3 cycles finally HIFU was given; in the control group only TACE+PVE was given. Response (CR+PR), and disease control rate (CR+PR+SD), side effects, overall survival and time to progress were calculated. RESULTS: Main side effects of both groups were nausea and vomiting. No treatment related death occurred. In the study group, 32 patients received TACE for overall 67 times, PVE 64 times, and HIFU 99 times; on average 2.1, 2 and 3.1 times for each patient, respectively. In the control group, 36 patients were given TACE 78 times and PVE 74 times, averaging 2.2 and 2.1 times per patient. Effective rate: 25.0% in study group and 8.3% in control group (p>0.05). Disease control rates were 71.9% and 44.4%, respectively (p<0.05). In patients with portal vein tumor thrombus, the rate reduced over 1/2 after treatment was 69.2%(9/13) in the study and 21.4%(3/14) in the control group (p<0.05). Rate of AFP reversion or decrease over 1/2 was 66.7%(16/24) in study and 37%(10/27) (p<0.05) in control group. Median survival time: 16 months in study and 10 months in control group. PFS was 7months in study and 3 months in control group. Log-rank test suggested that statistically significant difference exists between two groups (p=0.024). 1-, 2- and 3-year survival rates were 56.3%, 18.8% and 9.3% in study, while 30.6%, 5.6% and 0 in control group, respectively, with statistically significant difference between two groups (by Log-rank, p = 0.014). CONCLUSIONS: The treatment of TACE+PVE+HIFU sequential therapy for HCC increases response rate, prolong survival, and could thus be a safe and effective treatment for advanced cases.

Chemical characterization of Lycium barbarum polysaccharides and its inhibition against liver oxidative injury of high-fat mice.

In this study, we investigated chemical structure of Lycium barbarum polysaccharides and its modulatory effect on oxidative stress in high-fat mice. The polysaccharides mainly contained xylose and glucose. Little amount of rhamnose, mannose and galactose was observed. The Lycium barbarum polysaccharides had IR bands at 800-1200 cm(-1), 1450-1800 cm(-1), 2500-3000 cm(-1), and 3200-3600 cm(-1), which were distinctive absorptions of polysaccharides. Rats are fed with high-fat diet for 2 months. Results showed that blood and liver antioxidant enzymes activities and GSH level in model mice significantly decreased, and MDA level significantly increased (P<0.01) compared to normal control mice. Administration of Lycium barbarum polysaccharides significantly increased antioxidant enzymes activities and decreased MDA level in mice (P<0.01) compared to model group.

Effects of Glycyrrhiza glabra polysaccharides on immune and antioxidant activities in high-fat mice.

The purpose of this study was to investigate the immune and antioxidant activities of Glycyrrhiza glabra polysaccharides (GGP) in rats fed high-fat diet. The experiment was performed on four groups of growing Kunming mice. The results of the experiment showed a statistically significant decrease in serum antioxidant enzyme activities in high-fat group. Administration of GGP dose-dependently significantly enhanced immune and antioxidant enzyme activities in the GGP-treated mice compared to the high-fat model mice. It is concluded that GGP treatment can enhance immune activities, and reduce oxidative stress in high-fat mice.

[Safety and efficacy of QianlieanSuppository for chronic prostatitis of damp-heat and blood-stasis syndrome: a randomized, single-blind, parallel controlled, multi-centered phase III clinical trial].

OBJECTIVE: To evaluate the safety and efficacy of Qianliean Suppository in the treatment of chronic prostatitis of damp-heat and blood-stasis syndrome. METHODS: We conducted a randomized, single-blind, parallel-controlled, multi-centered clinical trial among 467 subjects, who were assigned to a trial group (n = 349) and a control group (n = 118), the former treated with Qianliean Suppository anally one pill per night for 28 days and the latter given Yejuhua Suppository in the same way. The efficacy was evaluated by the TCM syndrome, NIH-CPSI, main clinical symptoms and WBC count in EPS. RESULTS: After the treatment, the total rates of recovery, excellence and effectiveness for the TCM syndrome were 4.4%, 58.0% and 90.7% respectively in the trial group, significantly higher than 0.9%, 33.1% and 70.4% in the control group (P < 0.025). Remarkable decreases were observed in the NIH-CPSI total score and the scores on pain and discomfort, voiding symptoms and quality of life in the former group compared with the latter (P < 0.025). The trial group also showed a marked alleviation of such main chronic prostatitis symptoms as urgent micturition and perineal pain and discomfort (P < 0.05), as well as an obvious improvement (55.2%) of the WBC count in EPS as compared with 32.4% in the control group (P < 0.05). No serious adverse events occurred in either of the two groups (0.56% [2/349 ] vs 0.83% [1/118]). CONCLUSIONS: Qianliean Suppository is safe and effective for the treatment of chronic prostatitis of damp-heat and blood-stasis syndrome.

[Effect of varicocele on expression of apoptosis associated gene Bcl-2 and Bax in spermatogenic cells of adolescent rats].

OBJECTIVE: To study the effect of varicocel (VC) on expression of apoptosis associated gene Bcl-2 and Bax in spermatogenic cells of adolescent rats, and investigate the mechanism of the infertility resulting from varicocele. METHODS: The varicocele model was created by partial ligation of the left renal vein in the adolescent rats, two and four and eight weeks after creation of the varicocele model, the expressions of Bcl-2 and Bax were detected by immunohistochemical method. RESULTS: With the duration of varicocele model, the Bcl-2 expression in experiment group was decreased as compared with that in control group. And in experiment group, the Bcl-2 expression level was lower in left testis than in right testis. But Bax expression in experiment group was increased as compared with that in control group, and in experiment group, the Bax expression level was higher in left testis than in right testis. CONCLUSION: Experimental varicocele could change obviously expression of apoptosis associated gene Bcl-2 and Bax in spermatogenic cells of adolescent rats.