Disruption of perineuronal nets increases the frequency of sharp wave ripple events.

Hippocampal sharp wave ripples (SWRs) represent irregularly occurring synchronous neuronal population events that are observed during phases of rest and slow wave sleep. SWR activity that follows learning involves sequential replay of training-associated neuronal assemblies and is critical for systems level memory consolidation. SWRs are initiated by CA2 or CA3 pyramidal cells (PCs) and require initial excitation of CA1 PCs as well as participation of parvalbumin (PV) expressing fast spiking (FS) inhibitory interneurons. These interneurons are relatively unique in that they represent the major neuronal cell type known to be surrounded by perineuronal nets (PNNs), lattice like structures composed of a hyaluronin backbone that surround the cell soma and proximal dendrites. Though the function of the PNN is not completely understood, previous studies suggest it may serve to localize glutamatergic input to synaptic contacts and thus influence the activity of ensheathed cells. Noting that FS PV interneurons impact the activity of PCs thought to initiate SWRs, and that their activity is critical to ripple expression, we examine the effects of PNN integrity on SWR activity in the hippocampus. Extracellular recordings from the stratum radiatum of horizontal murine hippocampal hemisections demonstrate SWRs that occur spontaneously in CA1. As compared with vehicle, pre-treatment (120 min) of paired hemislices with hyaluronidase, which cleaves the hyaluronin backbone of the PNN, decreases PNN integrity and increases SWR frequency. Pre-treatment with chondroitinase, which cleaves PNN side chains, also increases SWR frequency. Together, these data contribute to an emerging appreciation of extracellular matrix as a regulator of neuronal plasticity and suggest that one function of mature perineuronal nets could be to modulate the frequency of SWR events.

Analysis of Pre- and Postoperative Pain Variation in Osteoporotic Vertebral Compression Fracture Patients Undergoing Kyphoplasty.

BACKGROUND Balloon kyphoplasty (KP) has been widely applied in the treatment of elderly patients with osteoporosis vertebral compression fracture (OVCF), but there has been little research on the pain relief effect. Therefore, we performed this study of patients who received KP. The study included a set of fluoroscopy tests and follow-up evaluation, which aimed to verify the effectiveness of kyphoplasty in controlling back pain associated with OVCFs. MATERIAL AND METHODS Forty-three OVCF patients underwent kyphoplasty: 21 were allocated to an intervention group and 22 were allocated to a control group, and the 2 groups received treatment with different KP instruments. The variation of vertebral height was measured on X-ray and change of signal of MRI was recorded. The pain was assessed by VAS score and diagram, and physical function was evaluated by ODI. The complications after surgery were recorded and collated during 2 years of follow-up. RESULTS The intervention group showed no significant difference on the VAS and ODI compared to the control group (p>0.05). There was no difference in the VAS with different degrees of radiological change (p>0.05). Signal change on MRI imaging was rare. CONCLUSIONS Kyphoplasty is a positive way to alleviate early-onset OVCF pain. The change of BME extent in the treated level is unrelated to the relief of back pain after KP.

Percutaneous Balloon Kyphoplasty in Treatment of Painful Osteoporotic Occult Vertebral Fracture: A Retrospective Study of 89 Cases.

BACKGROUND The definition of a vertebral fracture is usually based on the presence of a deformation of the vertebral body and this can be misleading in the presence of a fracture without radiologic collapse with the definition of occult osteoporotic vertebral fractures (OOVFs). STIR sequence of MRI images showing hyperintensity signal was the most confirmative screening examination used to determine the presence of painful OOVFs. To date, clinical management of OOVFs has been rarely discussed. MATERIAL AND METHODS Between 2011 and 2013, 89 patients suffering from painful OOVFs underwent 142 percutaneous balloon kyphoplasty (PKP) procedures. Outcome data (mean variation of anterior and middle vertebral body height, visual analog scale [VAS] scores, Oswestry Disability Index [ODI] scores, and SF-36 scores) were recorded preoperatively, postoperatively, and at 1 month, 6 months, and 2 year after treatment, to evaluate the results. RESULTS We successfully treated 89 patients (142 vertebral bodies) with PKP. Cement leakages were observed in 12 (8.45%) treated vertebral bodies and there were 5 new adjacent vertebral fractures during the follow-up period. The mean variation of anterior and middle vertebral body height changed from 96.5±3.4% preoperatively to 97.2±2.5% postoperatively (p>0.05) and from 96.3±2.8% preoperatively to 97.9±3.1% postoperatively (p>0.05), respectively. The mean VAS scores were reduced significantly from pre-surgery to post-surgery (8.3±1.2 to 2.9±0.7; p<0.05), as was the ODI score (76.4±12.5 to 26.7±5.6; p<0.05). The SF-36 scores, including Bodily Pain (BF), Vitality (VT), Physical Function (PF), and Social Functioning (SF), all showed notable improvement (P<0.05). These variations were maintained during the 2-year follow-up period. CONCLUSIONS PKP is a safe and effective method in the treatment of painful OOVFs.

Hypercrosslinked porous polyporphyrin by metal-free protocol: characterization, uptake performance, and heterogeneous catalysis.

Through metal-free protocol, hypercrosslinked porous polyporphyrin with permanent porosity was obatined via the Friedel-Crafts alkylation of tetracarbazolylporphyrin using formaldehyde dimethyl acetal as an external cross-linker. Its chemical structure and porosity was well characterized and confirmed. The BET specific surface area value of HCP-TCPP is 1050 m2 g-1 and related dominant pore size is centered at 0.63 nm. The adsorption amount of methanol by HCP-TCPP is high up to 800 mg g-1 (about 25.0 mmol g-1) at its saturated vapor pressure, which is higher than that of toluene (600 mg g-1, 6.5 mmol g-1). Further study indicates that polymer HCP-TCPP, possessing the high BET specific surface area and total pore volume, exhibits good hydrogen uptake of 3.44 wt % (77 K) and high carbon dioxide uptake of 41.1 wt % (298 K) at 18.0 bar. Besides, the obtained porous polymer can also be used as an effective heterogeneous catalyst for the Knoevenagel condensation between various aldehydes and malononitrile.

[Chemical constituents of Scrophularia ningpoensis root].

OBJECTIVE: To investigate the chemical constituents from Scrophularia ningpoensis root. METHODS: The compounds were isolated and purified by silica gel and Sephadex LH-20 column chromatography. The structures of these compounds were elucidated on the basis of spectroscopic analysis. RESULTS: Eleven compounds were isolated and identified as vanillin (1), eugenol (2), isoeugenol methyl ether(3), ferulic acid(4), benzoic acid(5), syringic acid(6) ,rhamnopyranosyl vanilloyl(7), syringic acid-4-O-alpha-L-rhamnopyr-anoside(8), beta-sitosterol(9), adenosine (10) and dibutyl phthalate(11). CONCLUSION: Compound 1-3 and 6-8 are obtained from this plant for the first time.

[Rationality of the processing methods of aconiti lateralis radix (Fuzi) based on chemical analysis].

In this study, we explored the rationality of processing methods and mechanism of Aconiti Lateralis Radix (Fuzi) through comparing the chemical contents of diester alkaloids (DAs) and monoester alkaloids (MAs) in the raw material of Fuzi and its processed products. The results showed that the toxicity potency of MAs is at least lower than 1/64 to 1/180 of the toxicity potency of DAs. The contents of DAs in processed Fuzi decreased to 1/76.5 to 1/38.3 of the value of raw Fuzi. The contents of MAs in processed Fuzi significantly increased by 4.6 to 5.2 fold or basically the same as that of the raw Fuzi. The values of MAs/DAs of processed Fuzi were enhanced by 30 to 390 fold of the raw Fuzi. It was found that the contents of DAs were insignificantly different between "Wu dan fu pian" (steaming or stir-frying without Danba) and "Dan fu pian" (steaming or stir-frying with Danba). The result suggested that the abilities of "eliminating toxicity" of different processing methods were equivalent at all. In contrast, the contents of MAs contained in "Wu dan fu pian" were of 5.3 to 8.7 fold higher than the values in "Dan fu pian". This result suggested the processing method by steaming or stir-frying without Danba might have better effect for "conserving property" than the method processed with Danba stipulated by China Pharmacopoeia. We believe that the new processing method without Danba can be recommended in further application due to it offers a simple procedure and it will not introduce inorganic impurities in the products.

The Prevalence of Rodents Orientia tsutsugamushi in China During Two Decades: A Systematic Review and Meta-Analysis.

Background: Orientia tsutsugamushi is a zoonotic intracellular pathogen that requires parasitism in eukaryotic cells to reproduce. In recent years, tsutsugamushi disease reported in many places nationwide has crossed the Yangtze River, continuously, spreading to the North China. Now this phenomenon has aroused people's attention. Materials and Methods: In this study, meta-analysis was used to analyze the infection of rodents (vectors) in China, to clarify the transmission rule of O. tsutsugamushi. Results: This study included literature from six databases (PubMed, Web of Science, Science Direct, Wanfang, CNKI, and VIP). A total of 55 articles were included in the study from 610 retrieved articles. The total infection rate of O. tsutsugamushi in rodents was 5.5% (1206/20,620, 95% confidence interval [CI]: 0.0553-0.0617). The prevalence of O. tsutsugamushi in rodents before 2013 (7.73%, 95% CI: 4.11-12.37) was higher than after 2013 (2.11%, 95% CI: 0.64-4.41). O. tsutsugamushi spread among a variety of rodents, among which Rattus losea (13.3%, 95% CI: 4.33-26.26), Rattus tanezumi (5.69%, 95% CI: 1.37-12.72), and Apodemus agrarius (5.32%, 95% CI: 2.26-9.58) infection rate was higher. Kawasaki (8.32%, 95% CI: 1.42-20.17), Karp (7.36%, 95% CI: 2.62-14.22), Kato (2.54%, 95% CI: 0.08-8.28), and Gilliam (2.13%, 95% CI: 0.42-5.09) were the main prevalent genotypes in China. The prevalence of O. tsutsugamushi in rodents was seasonal, increasing gradually in summer (2.39%, 95% CI: 0.46-5.77), peaking in autumn (4.59%, 95% CI: 1.15-10.16), and then declining. The positive rate of immunofluorescence assay (25.07%, 95% CI: 8.44-46.88) was the highest among the detection methods, and it was statistically significant (p < 0.05). Based on the subgroup of geographical factors and climatic factors, the probability of O. tsutsugamushi infection in rodents was the highest when the temperature >19℃ (8.20%, 95% CI: 1.22-20.52), the altitude <100 millimeters (7.23%, 95% CI: 3.45-12.26), the precipitation >700 millimeters (12.22%, 95% CI: 6.45-19.50), and the humidity 60-70% (7.80%, 95% CI: 4.17-12.44). Conclusions: Studies have shown that rodents carrying O. tsutsugamushi are common. People should prevent and control rodents in life and monitor rodents carrying O. tsutsugamushi for a long time.

Research on fuzi based on animal thermotropism behavior to discover if it has fewer "hot" characteristics without Ganjiang.

OBJECTIVE: To investigate whether fuzi (Radix Aconiti Praeparata) has fewer "hot" characteristics when administered without Ganjiang (Rhizoma Zingiberis). METHODS: Differences in the thermotropism behaviors of mice treated either with fuzi (Radix Aconiti Praeparata), Ganjiang (Rhizoma Zingiberis) or the combination of the two given intragastrically were investigated using the Animal Thermotropism Behavior Surveillance System. The water intake volume, oxygen consumption volume, adenosine triphosphatase (ATPase) activity, total antioxidant capacity (T-AOC) and total superoxide dismutase (T-SOD) activity were determined during the investigation. RESULTS: When fuzi and ganjiang were administered together, the rate at which mice remained on a warm plate ("remaining rate") and the times and distances of their movement were all significantly reduced (P < 0.05). Compared with the Normal group, the reduction was 55.1%, 48.3% and 44.8%, while compared with the Fuzi group, the reduction was 57.6%, 34.3% and 36.0%, indicating that "cold" tropism was significantly increased. Compared with the normal and fuzi groups, the ATPase activity and the respiratory oxygen consumption volume of the fuzi + ganjiang group were significantly increased (P < 0.05), suggesting an improvement in energy metabolism and showing a "hot" characteristic when Fuzi and Ganjiang are present together. Additionally, the T-AOC and T-SOD activity were significantly enhanced (P < 0.05). CONCLUSION: The behavior of mice tending toward "cold" tropism can be regarded as a quantitative reflection of Fuzi having fewer characteristics consistent with a "hot" nature when not used with Ganjiang, the functional mechanism of which may be a change in the ATPase activity in liver tissue.

[Effects of simvastatin on expression of connective tissue growth factor in vitreous and retina of diabetic rats].

OBJECTIVE: To study the effects of simvastatin on the expression of connective tissue growth factor (CTGF) that cause fibrosis in the vitreous and retina after intravitreal injection in diabetic rats, and to explore the safety of this procedure. METHODS: It was an experimental study. Forty adult male Wistar rats were randomly divided into normal control group (10 rats) and diabetes mellitus group (30 rats). Four months later, according to whether treated with simvastatin or not, the diabetes mellitus group randomly divided into simvastatin intervention group (20 rats) and diabetic positive control group (10 rats). Simvastatin was injected into the vitreous in the simvastatin intervention group, but not in the diabetic positive control group. Seven days later, after the examination of electroretinogram (ERG), all rats were sacrificed, and their eyeballs were enucleated. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry method were performed to determine the expression of CTGF in the vitreous and retina. Terminal DNA transferase-mediated dUTP nick end labeling (TUNEL) method was used to detect apoptosis of retina cells. Concentration of CTGF in the vitreous, retinal expression of CTGF, retinal cellular apoptosis index, ERG-b wave and oscillatory potentials (OPs) of rats in each group were compared using analysis of variance LSD test methods. RESULTS: No systemic toxic reactions, no lens opacity and no endophthalmitis occurred after injection of simvastatin into the vitreous of rats. Concentrations of CTGF in vitreous of simvastatin intervention group, diabetes positive control group and normal control group rats were 359.21 µg/L, 478.47 µg/L and 210.78 µg/L, respectively (F = 252.366, P < 0.05). The levels of CTGF in the vitreous of simvastatin intervention group and diabetic positive control group was significantly higher than that of the normal control group and showed significant difference (t = 12.123, 23.816;P < 0.05). CTGF levels in simvastatin intervention group were significantly lower than those in diabetic positive control group, and the difference was statistically significant. (t = 11.693, P < 0.05). The results of immunohistochemical staining and TUNEL staining were negative in the normal control group. Retinal expression of CTGF in simvastatin intervention group and diabetic positive control group were (26.60 ± 2.95)% and (42.31 ± 2.59)%, respectively. Retinal expression of CTGF in simvastatin intervention group was reduced as compared to the diabetic positive control group, the difference was statistically significant (t = 12.112, P < 0.05). Retinal cellular apoptosis index of simvastatin intervention group and diabetic positive control group was 0.19 ± 0.02 and 0.25 ± 0.03, respectively. Retinal cellular apoptosis index of simvastatin intervention group was significantly lower than that in diabetic positive control group (t = 4.745, P < 0.05). ERG revealed no significant changes. In simvastatin intervention group as compared with diabetic positive control group. CONCLUSIONS: Simvastatin could inhibit the expression of CTGF in the vitreous body and retina in diabetic rats. Intravitreal injection of simvastatin is a relatively safe procedure.

The difference of auxiliary examination parameters between margin recurrence and granuloma on enhanced computed tomography after sublobar resection.

Background: Imaging examinations following sublobar resection of lung cancer often find thickened neoplasms around the resection margin. Identifying whether the neoplasms are postoperative recurrence or margin granulomas is vitally important. However, the identification mainly depends on the empirical judgment of the imaging department or clinicians in each clinical center at present, and there are few relevant studies, so it is hard to formulate a relatively unified standard. Therefore, we collected data from patients with thickened neoplasms around the resection margin after sublobar resection and sought to discover how to differentiate granulomas from tumor recurrence. Methods: We examined the clinical records of 15 patients with neoplasms around the margins which identified as malignant in auxiliary examination reports, and received second surgery after first sublobar resection. We collected their postoperative pathology and auxiliary examination parameters. The univariate predictors helpful in distinguishing between recurrence and granuloma were analyzed as a diagnostic test. Results: Of the 15 patients with neoplasms around the resection margin, six were diagnosed with benign granulomas, and nine were diagnosed with primary lung cancer recurrence. The results revealed that age, gender, specific surgical method, maximum standardized fluorodeoxyglucose uptake value (SUVmax), and follow-up time were not significantly different, but there were significant differences in enhanced computed tomography (CT) values in several analyses, which calculated by the hospital imaging system. The maximum CT values of the tumor recurrence and granuloma were 104.9±8.051 and 130.3±7.017 (P=0.045), the minimum CT values (15.67±5.113 vs. -17.17±4.826, P=0.0007) and in the floating range CT values (148.00±5.471 vs. 88.11±7.671, P<0.0001), respectively. Conclusions: Differentiating between tumor recurrence and granulomas after sublobar resection remains difficult. However, examining the differences in enhanced CT allows the clinician to make an informed diagnosis that aids further investigation and treatment.

Circular RNA hsa_circ_0003823 promotes the Tumor Progression, Metastasis and Apatinib Resistance of Esophageal Squamous Cell Carcinoma by miR-607/CRISP3 Axis.

Background: Circular RNAs (CircRNAs) have attracted a growing interest of research in cancer. The regulatory roles and mechanisms of circRNAs in progression, metastasis and drug resistance of esophageal squamous cell carcinoma (ESCC) needed to be clarified. Our previous study revealed the crucial role of Apatinib in ESCC therapy. However, the correlation between circRNAs and Apatinib resistance remained unclear. Methods: 3 pairs of tumor and paracancerous tissues of ESCC patients were used for RNA sequencing. Western blot analysis, RNA immunoprecipitation (RIP), dual-luciferase reporter assays, apoptosis and animal assays were conducted to confirm the roles and specific mechanisms of hsa_circ_0003823 as well as the effects of it on Apatinib sensitivity in ESCC. Results: Our results revealed that hsa_circ_0003823 was highly expressed in ESCC and associated with poor prognosis. Further results indicated that hsa_circ_0003823 promoted proliferation and metastasis ability of ESCC. In the section of mechanism experiments, hsa_circ_0003823 regulated CRISP3 by targeting microRNA-607 (miR-607) to promote progression of ESCC. Besides, we found that silencing hsa_circ_0003823 improved Apatinib sensitivity. hsa_circ_0003823 resulted in Apatinib resistance by miR-607/CRISP3 axis. Conclusions: In this study, we elucidated the function of hsa_circ_0003823 and its role in promoting tumor progression, metastasis and Apatinib resistance of ESCC through miR-607/CRISP3 axis.

Gentiopicroside alleviates cardiac inflammation and fibrosis in T2DM rats through targeting Smad3 phosphorylation.

BACKGROUND: Cardiac fibrosis is a major structural change observed in the heart of patients with type 2 diabetes mellitus (T2DM), ultimately resulting in heart failure (HF). Suppression of inflammation is an effective therapeutic strategy for treating cardiac fibrosis and HF. Gentiopicroside (GPS), the primary component of Gentiana manshurica Kitagawa, possess potent anti-inflammatory activity. However, its cardioprotective role remains elusive. PURPOSE: We explored the potential cardioprotective role of GPS in T2DM rats and its underlying mechanisms. METHODS: T2DM rats built by high-fat diet and streptozotocin were orally administered 25, 50, or 100 mg/kg GPS, daily for 8 weeks. The positive control drug was Metformin (200 mg/kg/day). Primary cardiac fibroblasts (CFs) were induced by high glucose (30 mM) and subsequently treated with GPS (100 µM). Cardiac function and pathological changes were analyzed using echocardiography and histological staining. Potential targets of GPS were predicted using Molecular docking. Real-time PCR as well as western blotting were applied to verify the expression of objective genes. RESULTS: All three doses reduced fasting blood glucose levels, but only 50 and 100 mg/kg GPS improved cardiac function and alleviated inflammation and fibrosis in T2DM rats. GPS (100 mg/kg) exhibited a better effect, similar to that of metformin. Mechanistically, binding between GPS and the MH2 domain of Smad3 blocked high glucose-induced Smad3 phosphorylation, thus attenuating inflammation, oxidative stress, and activation in CFs. CONCLUSION: We, for the first time, demonstrated that GPS improved cardiac function in T2DM rats and elucidated the underlying mechanism through which GPS targeted Smad3 phosphorylation to suppress inflammation and activation in CFs, thereby revealing the potential application of GPS in HF therapy.

Risk factors for postoperative wound infections of sacral chordoma after surgical excision.

STUDY DESIGN: A retrospective study, analyzing the risk factors for postoperative wound infections of the sacral chordoma after surgical excision. OBJECTIVE: To determine the preoperative, intraoperative, and patient characteristics that contribute to an increased risk of postoperative wound infection in patients undergoing sacral chordoma resection. SUMMARY OF BACKGROUND DATA: Postoperative wound infection after spinal operations is a dreaded complication. The risk factors have been investigated earlier, but the patients with sacral chordoma may be distinct. METHODS: Between January 1992 and December 2007, 45 patients with sacral chordomas were treated with surgical resection. Data regarding preoperative and intraoperative risk factors for postoperative wound infection were evaluated using univariate analysis and multivariable conditional logistic regression. Odds ratios with 95% confidence intervals and P values were calculated. RESULTS: Of the 45 patients with sacral chordoma, 16 (35.6%) acquired postoperative wound infection. Significant risk factors associated with postoperative wound infection in the univariate analysis included the following: albumin <3.0, previous surgery, operating time, instrumentation, and surgical team. Albumin<3.0, operating time >6 hours, and previous surgery were statistically significant in the multivariable model. CONCLUSIONS: Patients undergoing sacral tumor surgery may be at greater risk for developing wound complications. In this study, it seems that albumin<3.0, operating time >6 hours, and previous surgery may predict those patients that were more prone to developing postoperative wound infection. Using a single surgical team and no instrumentation seems to provide protection against postoperative wound infection in this patient population.

[Retinal cell apoptosis, microvascular changes and expression of connective tissue growth factor in experimental diabetic rats].

OBJECTIVE: To study the cell apoptosis and the expression of connective tissue growth factor (CTGF) in the retina of diabetic rats and to explore their contributions to the changes of microcirculation. METHODS: It was a experiment study. Fifty-five adult male Wistar rats were divided into two groups, normal control group (CON, 10 rats) and diabetes mellitus group (DM, 45 rats). The 30 surviving rats in the DM group were further divided into 3 groups based on the time of observation, 2 month (DM2), 4 month (DM4) and 6 month (DM6) groups, with 10 rats in each group. Cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). Expression of CTGF was determined by immunohistochemical study. Retinal vessels were observed by retinal digest stretched periodic acid Schiff (PAS) staining. RESULTS: Immunohistochemical staining and TUNEL staining revealed negative results in normal control group. Retinal cell apoptosis index increased gradually from DM2 to DM6, the differences between any two groups were statistically significant (t(2-4, 2-6, 4-6) = 21.432, 50.843, 29.410; P < 0.05). Expression of CTGF in the retina increased from DM2-DM6, the differences between any two groups were statistically significant (t(2-4, 2-6, 4-6) = 15.345, 26.316, 10.971; P < 0.05). PAS staining of retinal blood vessels obtained negative results in the CON and DM2 groups. Part of retinal capillaries were slightly stiff and narrow in DM4 group. Retinal capillaries in DM6 group were trunk stiff and were narrowed obviously. The number of pericytes was reduced in DM4, and progressed following the course of diabetes. The number of pericytes in the DM2 group did not different from that in the CON group (t = 0.875, P = 0.387). The number of pericytes in the DM4 and DM6 group were significantly decreased as compared to the CON group (t = 3.367, 6.667; P < 0.05). Retinal cellular apoptosis index had a significant positive correlation to the expression of CTGF (r = 0.958, P < 0.05). Number of pericytes was significantly correlated (negative correlation) with retinal cellular apoptosis index and the expression of CTGF (r = -0.540, -0.595; P < 0.05). CONCLUSIONS: The appearances of cellular apoptosis and fibrosing factor CTGF in the retina of diabetic rats occurred earlier than the changes of microcirculation and the number of capillary pericytes.

Apatinib induces endoplasmic reticulum stress-mediated apoptosis and autophagy and potentiates cell sensitivity to paclitaxel via the IRE-1α-AKT-mTOR pathway in esophageal squamous cell carcinoma.

BACKGROUND: Apatinib, a novel vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, has been approved for the treatment of metastatic gastric cancer and other tumors. Apatinib exerts antiproliferative and proapoptotic effects in different kinds of cancer cells. However, the molecular mechanisms by which apatinib effective against esophageal squamous cell carcinoma (ESCC) have only been partially researched and whether it has a sensitizing effect on paclitaxel remains unclear. MATERIALS AND METHODS: The effects of apatinib or paclitaxel on endoplasmic reticulum (ER) stress, autophagy, apoptosis and proliferation of ESCC cell lines were evaluated. Western blot and immunohistochemistry analyses were performed to detect the expression of related genes. The weight and volume of xenograft tumors in mice were measured. RESULTS: In the current study, we elucidated the antiproliferative and ER-stress-mediated autophagy-inducing effects of apatinib on ECA-109 and KYSE-150 esophageal squamous cancer cells and identified the underlying mechanisms of its action. We demonstrated that apatinib not only inhibited the proliferation and induced the apoptosis of ESCC cells, but also activated ER stress and triggered protective autophagy. Moreover, inhibiting autophagy by chloroquine (CQ) enhanced the apatinib-induced apoptosis of ESCC cells through the IRE-1α-AKT-mTOR pathway. In addition, we showed, for the first time, the paclitaxel combined with apatinib and CQ exhibited the best antitumor effect on ESCC both in vivo and in vitro via the IRE-1α-AKT-mTOR pathway. CONCLUSIONS: Our data showed that apatinib induced ER stress, autophagy and apoptosis in ESCC. Inhibiting autophagy by CQ enhanced apatinib-induced apoptosis. The combination of apatinib and CQ sensitized ESCC cells to paclitaxel to induce apoptosis through the IRE-1α-AKT-mTOR signaling pathway, thus providing the basis for its use in innovative anticancer therapeutic strategies.

Diffusion-weighted MRI and 18F-FDG PET/CT in assessing the response to neoadjuvant chemoradiotherapy in locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is a currently widely used strategy for locally advanced esophageal cancer (EC). However, the conventional imaging methods have certain deficiencies in the evaluation and prediction of the efficacy of nCRT. This study aimed to explore the value of functional imaging in predicting the response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Fifty-four patients diagnosed with locally advanced ESCC from August 2017 to September 2019 and treated with nCRT were retrospectively analyzed. DW-MRI scanning was performed before nCRT, at 10-15 fractions of radiotherapy, and 4-6 weeks after the completion of nCRT. 18F-FDG PET/CT scans were performed before nCRT and 4-6 weeks after the completion of nCRT. These 18F-FDG PET/CT and DW-MRI parameters and relative changes were compared between patients with pathological complete response (pCR) and non-pCR. RESULTS: A total of 8 of 54 patients (14.8%) were evaluated as disease progression in the preoperative assessment. The remaining forty-six patients underwent operations, and the pathological assessments of the surgical resection specimens demonstrated pathological complete response (pCR) in 10 patients (21.7%) and complete response of primary tumor (pCR-T) in 16 patients (34.8%). The change of metabolic tumor volume (∆MTV) and change of total lesion glycolysis (∆TLG) were significantly different between patients with pCR and non-pCR. The SUVmax-Tpost, MTV-Tpost, and TLG-Tpost of esophageal tumors in 18F-FDG PET/CT scans after neoadjuvant chemoradiotherapy and the ∆ SUVmax-T and ∆MTV-T were significantly different between pCR-T versus non-pCR-T patients. The esophageal tumor apparent diffusion coefficient (ADC) increased after nCRT; the ADCduring, ADCpost and ∆ADCduring were significantly different between pCR-T and non-pCR-T groups. ROC analyses showed that the model that combined ADCduring with TLG-Tpost had the highest AUC (0.914) for pCR-T prediction, with 90.0% and 86.4% sensitivity and specificity, respectively. CONCLUSION: 18F-FDG PET/CT is useful for re-staging after nCRT and for surgical decision. Integrating parameters of 18F-FDG PET/CT and DW-MRI can identify pathological response of primary tumor to nCRT more accurately in ESCC.

[Prognosis of patients with intracerebral hemorrhage].

OBJECTIVE: To study the related factors of patients with intracerebral hemorrhage (ICH) so as to guide treatment and predict prognosis. METHODS: The prognostic factors of 463 cases with intracerebral hemorrhage were analyzed with single factor and Logistic regression analyses. RESULTS: Age, Glasgow coma scale, amount of hemorrhage, NIHSS score, mean arterial blood pressure, with or without ventricular breakage, with or without midline shift and the incidence of complications at random blood glucose levels were analyzed for the correlation with the prognosis of patients. The poor prognosis group had significant differences with the good prognosis group with regards to these factors. The average age of patients with a poor prognosis was 71 years old, the average hematoma volume 29 ml and the average GCS score 11.2 versus 65 years old, 15 ml, 15.1 for those with a good prognosis (P < 0.05). Logistic regression analysis showed that age, amount of hemorrhage and disturbance of consciousness was an independent adverse prognostic factor for cerebral hemorrhage at three months. The OR values were 1.32, 8.66 and 1.08 respectively. CONCLUSION: The etiologies of ICH are diverse. Maintaining normal blood pressure is an important preventive measure for ICH. Hematoma volume, disturbance of consciousness and age may be used to predict the prognosis of cerebral hemorrhage.

Minimally Invasive Pedicle Screw Fixation Combined with Percutaneous Kyphoplasty Under O-Arm Navigation for the Treatment of Metastatic Spinal Tumors with Posterior Wall Destruction.

OBJECTIVE: To evaluate the safety and efficacy of O-arm-guided minimally invasive pedicle screw fixation combined with percutaneous kyphoplasty for metastatic spinal tumors with posterior wall destruction. METHODS: Patients who underwent minimally invasive pedicle screw fixation combined with percutaneous kyphoplasty for pathological vertebral fractures with posterior wall defects from January 2015 to December 2017 were followed up for 1 year. Visual analogue scale (VAS), SF-36 scores, middle vertebral height, posterior vertebral height, and the accuracy of pedicle screws were assessed preoperatively, postoperatively, and 1 year after surgery. The operation time, time from operation to discharge, blood loss, volume of bone cement, and leakage of bone cement were recorded. RESULTS: Twenty-three patients (13 females and 10 males) who met our criteria were followed up for 1 year. The operation time of these patients was 162.61 ± 33.47 min, the amount of bleeding was 230.87 ± 93.76 mL, the time from operation to discharge was 4.35 ± 2.42 days, and the volume of bone cement was 3.67 ± 0.63 mL. The VAS score decreased from 7.04 ± 1.07 to 2.65 ± 0.93 before surgery (P = 0.000) and remained at 2.57 ± 0.79 1 year after surgery. Compared with the preoperative SF-36 scores for physical pain, physiological function, energy, and social function, the postoperative scores were significantly improved (P = 0.000). The height of the middle vertebral body increased from 14.47 ± 2.96 mm before surgery to 20.18 ± 2.94 mm (P = 0.000), and remained at 20.44 to 3.01 mm 1 year after surgery. The height of the posterior vertebral body increased from 16.56 ± 3.07 mm before operation to 22.79 ± 4.00 mm (P = 0.000), and 22.45 ± 3.88 mm 1 year after surgery. The 23 patients had a total of 92 pedicle screws; 85 screws were Grade A and 7 screws were Grade B. There was no leakage of bone cement after surgery. CONCLUSION: In the short term, O-arm-guided minimally invasive pedicle screw fixation combined with kyphoplasty is safe and effective in the treatment of metastatic spinal tumors with posterior wall destruction.

Could cells from menstrual blood be a new source for cell-based therapies?

Human endometrium is a highly regenerative tissue and contains a low number of cells which have high replicative ability and differentiation efficiency. This has been identified by many scientists. When the fresh growth of tissue and blood vessels is shed during each menstrual cycle, some cells with regenerative capabilities are present. Reports have also indicated that these cells possess the capacity to trans-differentiate into mesodermal, ectodermal and endodermal lineages by using standard commercially available culture reagents and methodologies. Given the ease of extraction and pluripotency of this cell population, we propose it as a novel alternative to current cells sources for cell-based therapies.

Synthesis of water-soluble fluorescent polymeric glycoconjugate for the detection of cholera toxin.

Considering inherence optical properties of adjoint polyfluorenes and special functions of water-soluble conjugated glycopolymers, a triazole chain glycoconjugate via one-pot method were rapidly synthesized to prepare a lactate ligand polyfluorene with a clear fluorescent label by a nickel-catalyzed Yamamoto coupling polymerization. The water solubility and biocompatibility of the glycoconjugated polymer were ameliorated when the lactose group introduced as the side chain of the conjugated polymer. As a fluorescent multivalent system of glycoconjugates containing pyranogalactose groups, the interaction between pyranogalactose group and cholera toxin B subunit was studied by fluorescence spectrophotometric titration. PF-Lac has a broad application prospect in the check of cholera toxin and the study of glycoprotein interaction.