PHLDA2 overexpression facilitates senescence and apoptosis via the mitochondrial route in human nucleus pulposus cells by regulating Wnt/ß-catenin signalling pathway.

Low back pain is a common clinical symptom of intervertebral disc degeneration (IVDD), which seriously affects the quality of life of the patients. The abnormal apoptosis and senescence of nucleus pulposus cells (NPCs) play important roles in the pathogenesis of IVDD. PHLDA2 is an imprinted gene related to cell apoptosis and tumour progression. However, its role in NPC degeneration is not yet clear. Therefore, this study was set to explore the effects of PHLDA2 on NPC senescence and apoptosis and the underlying mechanisms. The expression of PHLDA2 was examined in human nucleus pulposus (NP) tissues and NPCs. Immunohistochemical staining, magnetic resonance imaging imaging and western blot were performed to evaluate the phenotypes of intervertebral discs. Senescence and apoptosis of NPCs were assessed by SA-ß-galactosidase, flow cytometry and western blot. Mitochondrial function was investigated by JC-1 staining and transmission electron microscopy. It was found that the expression level of PHLDA2 was abnormally elevated in degenerated human NP tissues and NPCs. Furthermore, knockdown of PHLDA2 can significantly inhibit senescence and apoptosis of NPCs, whereas overexpression of PHLDA2 can reverse senescence and apoptosis of NPCs in vitro. In vivo experiment further confirmed that PHLDA2 knockdown could alleviate IVDD in rats. Knockdown of PHLDA2 could also reverse senescence and apoptosis in IL-1ß-treated NPCs. JC-1 staining indicated PHLDA2's knockdown impaired disruption of the mitochondrial membrane potential and also ameliorated superstructural destruction of NPCs as showed by transmission electron microscopy. Finally, we found the PHLDA2 knockdown promoted Collagen-II expression and suppressed MMP3 expression in NPCs by repressing wnt/ß-catenin pathway. In conclusion, the results of the present study showed that PHLDA2 promotes IL-1ß-induced apoptosis and senescence of NP cells via mitochondrial route by activating the Wnt/ß-catenin pathway, and suggested that therapy targeting PHLDA2 may provide valuable insights into possible IVDD therapies.

The accuracy and effectiveness of automatic pedicle screw trajectory planning based on computer tomography values: an in vitro osteoporosis model study.

BACKGROUND: Pedicle screw placement in patients with osteoporosis is a serious clinical challenge. The bone mineral density (BMD) of the screw trajectory has been positively correlated with the screw pull-out force, while the computer tomography (CT) value has been linearly correlated with the BMD. The purpose of this study was to establish an in vitro osteoporosis model and verify the accuracy and effectiveness of automated pedicle screw planning software based on CT values in this model. METHODS: Ten vertebrae (L1-L5) of normal adult pigs were randomly divided into decalcification and control groups. In the decalcification group, the vertebral bodies were decalcified with Ethylenediaminetetraacetic acid (EDTA) to construct an in vitro osteoporosis model. In the decalcification group, automatic planning (AP) and conventional manual planning (MP) were used to plan the pedicle screw trajectory on the left and right sides of the pedicle, respectively, and MP was used on both sides of the control group. CT values of trajectories obtained by the two methods were measured and compared. Then, 3D-printed guide plates were designed to assist pedicle screw placement. Finally, the pull-out force of the trajectory obtained by the two methods was measured. RESULTS: After decalcification, the BMD of the vertebra decreased from - 0.03 ± 1.03 to - 3.03 ± 0.29 (P < 0.05). In the decalcification group, the MP trajectory CT value was 2167.28 ± 65.62 Hu, the AP trajectory CT value was 2723.96 ± 165.83 Hu, and the MP trajectory CT value in the control group was 2242.94 ± 25.80 Hu (P < 0.05). In the decalcified vertebrae, the screw pull-out force of the MP group was 48.6% lower than that of the control group (P < 0.05). The pull-out force of the AP trajectory was 44.7% higher than that of the MP trajectory (P < 0.05) and reached 97.4% of the MP trajectory in the control group (P > 0.05). CONCLUSION: Automatic planning of the pedicle screw trajectory based on the CT value can obtain a higher screw pull-out force, which is a valuable new method of pedicle screw placement in osteoporotic vertebre.

Does MIS-TLIF or TLIF result in better pedicle screw placement accuracy and clinical outcomes with navigation guidance?

BACKGROUND: Although previous studies have suggested that navigation can improve the accuracy of pedicle screw placement, few studies have compared navigation-assisted transforaminal lumbar interbody fusion (TLIF) and navigation-assisted minimally invasive TLIF (MIS-TLIF). The entry point of pedicle screw insertion in navigation-assisted MIS-TLIF (NM-TLIF) may deviate from the planned entry point due to an uneven bone surface, which may result in misplacement. The purpose of this study was to explore the pedicle screw accuracy and clinical consequences of MIS-TLIF and TLIF, both under O-arm navigation, to determine which surgical method is better. METHODS: A retrospective study of 54 patients who underwent single-segment NM-TLIF or navigation-assisted TLIF (N-TLIF) was conducted. In addition to the patients' demographic characteristics, intraoperative indicators and complications, the Oswestry Disability Index (ODI) and visual analog scale (VAS) score were recorded and analyzed preoperatively and at the 1-, 6-, and 12-month and final postoperative follow-ups. The clinical qualitative accuracy and absolute quantitative accuracy of pedicle screw placement were assessed by postoperative CT. Multifidus muscle injury was evaluated by T2-weighted MRI. RESULTS: Compared with N-TLIF, NM-TLIF was more advantageous in terms of the incision length, intraoperative blood loss, drainage volume, time to ambulation, length of hospital stay, blood transfusion rate and analgesia rate (P < 0.05). The ODI and VAS scores for low back pain were better than those of N-TLIF at 1 month and 6 months post-surgery (P < 0.05). There was no significant difference in the clinical qualitative screw placement accuracy (97.3% vs. 96.2%, P > 0.05). The absolute quantitative accuracy results showed that the axial translational error, sagittal translational error, and sagittal angle error in the NM-TLIF group were significantly greater than those in the N-TLIF group (P < 0.05). The mean T2-weighted signal intensity of the multifidus muscle in the NM-TLIF group was significantly lower than that in the N-TLIF group (P < 0.05). CONCLUSIONS: Compared with N-TLIF, NM-TLIF has the advantages of being less invasive, yielding similar or better screw placement accuracy and achieving better symptom relief in the midterm postoperative recovery period. However, more attention should be given to real-time adjustment for pedicle insertion in NM-TLIF rather than just following the entry point and trajectory of the intraoperative plan.

Relationships between rumen microbes, short-chain fatty acids, and markers of white adipose tissue browning during the cold season in grazing Mongolian sheep (Ovisaries).

Mongolian sheep are characteristically cold-tolerant and they partially depend on seasonal browning of white adipose tissue (WAT) to acclimate to cold environments. The present work aimed to examine the rumen microbes, rumen fermentation profile, and relationships between the rumen microbiota, short-chain fatty acids (SCFAs), and markers of WAT browning and are thus conducive to exploring the plateau environment adaptability of Mongolian sheep in the cold season. A comparative analysis of the rumen microbes and SCFAs in the cold and warm seasons was conducted. Rumen microbes were analyzed using Illumina sequencing of the 16S rRNA gene. Ruminal SCFAs were determined by gas chromatography. Spearman's correlation test was used to determine the relationships between the rumen microbiota, SCFAs, and markers of WAT browning. Microbial 16S rRNA sequencing revealed a marked shift in rumen microbiota composition between the two seasons, and the bacteria were characterized by increased levels of the Actinobacteria and genera Christensenellaceae R-7 group, Ruminococcaceae UCG-011, Rikenellaceae RC9 gut group, Papillibacter, and Butyrivibrio 2 and reduced levels of Prevotella 1 and Ruminococcaceae UCG-014 in the cold season (P<0.05). Furthermore, the concentrations of SCFAs such as acetate and butyrate were significantly increased in the cold season (P<0.001 and P<0.05, respectively). Correlation analysis demonstrated that the relative abundances of the Actinobacteria and the genera Christensenellaceae R-7 group, Butyrivibrio 2, Ruminococcaceae UCG-002, and Ruminococcaceae UCG-011, identified as members of the Christensenellaceae, Lachnospiraceae, and Ruminococcaceae families (all within Firmicutes), were positively correlated with markers of browning in either retroperitoneal WAT or perirenal WAT, and acetate was positively correlated with Ruminococcaceae UCG-011 and Butyrivibrio 2 and markers of browning in either retroperitoneal WAT or perirenal WAT. Overall, there are distinct relationships between the rumen microbiota, ruminal SCFAs and markers of WAT browning during the cold season in grazing Mongolian sheep.

Role of white adipose tissue browning in cold seasonal acclimation in grazing Mongolian sheep (Ovisaries).

Mongolian sheep are characteristically cold-tolerant and thus can survive well and maintain genetic stability in the extremely cold environment of the Mongolian Plateau. However, the adaptive mechanism of Mongolian sheep during the cold season in the plateau environment remains unknown. Browning of white adipose tissues (WAT) can trigger nonshivering thermogenesis as a potential strategy to promote an animal's tolerance to cold environments. Thus, a comparative analysis of the genes and proteins of uncoupling protein 1 (UCP1)-dependent and UCP1-independent browning pathways, mitochondrial biogenesis, lipogenic and lipolytic processes of WAT from grazing Mongolian sheep in the cold and warm seasons was conducted. We found seasonal browning of both retroperitoneal WAT and perirenal WAT, and the signalling of the process was mainly transduced by the UCP1- dependent pathway, primarily reflected in the upregulated gene levels of UCP1 and peroxisome proliferative activated receptor gamma coactivator 1 alpha (PGC-1α). In addition, the mean adipocyte diameter and mRNA expression of lipogenic genes in both interscapular WAT and subcutaneous WAT were significantly elevated during the cold season. The findings of this study demonstrate that grazing Mongolian sheep could depend on seasonal browning of both retroperitoneal WAT and perirenal WAT together with the expansion of both interscapular WAT and subcutaneous WAT to acclimate to cold environments of the Mongolian Plateau.

Novel through-the-scope twin clip for the closure of GI wounds: the first experimental survival study in pigs (with videos).

BACKGROUND AND AIMS: We developed a through-the-scope twin clip (TTS-TC) for closing GI wounds. The objective of this study was to evaluate the efficacy and safety of the TTS-TC in GI wound closure. METHODS: GI nonperforating and perforating wounds (≥2.5 cm) were created in live pigs. TTS-TCs were used to convert the large wounds into small wounds. The remaining small wounds were closed using conventional through-the-scope clips (TTSCs). The follow-up period was 1 month. Location and size of the wound, time of wound closure, intraoperative and postoperative adverse events, and conditions of wound healing were investigated. RESULTS: Thirteen wounds were created in 5 live pigs, including 2 gastric nonperforating and 3 perforating wounds and 5 large intestinal nonperforating and 3 perforating wounds. The mean long and short diameters of the wounds were 4.1 (± .9) cm and 3.4 (± .7) cm, respectively. All wounds were successfully closed using the TTS-TCs combined with TTSCs. The total mean time for wound closure was 9.2 (± 5.3) minutes, and the mean time for using the TTS-TCs was 3.9 (± 4.7) minutes. During the 1-month follow-up period, no bleeding, perforation, or death occurred; all wounds healed with scar formation; and all TTS-TCs detached spontaneously. CONCLUSIONS: The TTS-TC was successfully used to close large-sized GI wounds. The TTS-TC is a promising tool for large-size wound closure under flexible endoscopy.

Efficacy and Safety of Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Liver Disease: a Meta-Analysis and Systematic Review.

BACKGROUND: Liver disease is associated with increased bleeding risk. The efficacy and safety of direct oral anticoagulants (DOACs) is a subject of contention in atrial fibrillation (AF) patients with liver disease. METHODS: Electronic databases (PubMed, Embase, and Cochrane Library) were searched to retrieve studies on the efficacy and safety of DOACs versus warfarin in AF patients with liver disease from January 1980 to April 2020. A meta-analysis was conducted using a random-effects model. RESULTS: Six studies involving 41,859 patients were included. Compared with warfarin, DOACs demonstrated significant reduction in ischemic stroke (HR, 0.68; 95% CI (0.54-0.86)), major bleeding (0.74 (0.59-0.92)), and intracranial hemorrhage (ICH) (0.48 (0.40-0.58)), with no significant effect on gastrointestinal bleeding (P = 0.893) in AF patients with liver disease. Similar results were observed in regular-dose, reduced-dose, and active liver disease subgroups, albeit Asian patients had a slight reduction in major bleeding (P = 0.055). Furthermore, the pooled estimates of individual DOAC subgroups indicated that dabigatran and apixaban led to greater safety in major bleeding (P < 0.001), ICH (P < 0.001), and gastrointestinal bleeding (P < 0.005) in these patients. The same trends were observed in AF patients with cirrhosis. CONCLUSIONS: Our findings suggest that DOACs significantly reduce the risk of ischemic stroke, major bleeding, and ICH, with no significant effect on the risk of gastrointestinal bleeding in AF patients with liver disease compared with warfarin.

Roles of multimodal intra-operative neurophysiological monitoring (IONM) in percutaneous endoscopic transforaminal lumbar interbody fusion: a case series of 113 patients.

BACKGROUND: Despite the wide use of intraoperative neurophysiological monitoring (IONM) in spinal surgeries, the efficacy of IONM during percutaneous endoscopic transforaminal lumbar interbody fusion (PE-TLIF) surgery in detecting postoperative neurological deficits has not been well characterized. METHODS: MIONM data from 113 consecutive patients who underwent PE-TLIF surgeries between June 2018 and April 2020 were retrospectively reviewed. Postoperative neurological deficits were documented and analyzed, and the efficacy and specificity of various IONM techniques were compared. RESULTS: Of the 113 consecutive patients, 12 (10.6%) with IONM alerts were identified. The MIONM sensitivity and specificity were 100 and 96.2%, respectively. The frequency of neurological complications, including minor deficits, was 6.2% (n = 7); all of the neurological complications were temporary. The ability of single IONM modalities to detect neurological complications varied between 25.0 and 66.6%, whereas that of all modalities was 100%. CONCLUSIONS: MIONM is more effective and accurate than unimodal monitoring in assessing nerve root function during PE-TLIF surgeries, reducing both neurological complications and false-negative findings. We recommend MIONM in PE-TLIF surgeries.

In vivo real-time diagnosis of endoscopic ultrasound-guided needle-based confocal laser endomicroscopy in gastric subepithelial lesions.

BACKGROUND AND AIM: The effect of real-time analysis of needle-based confocal laser endomicroscopy (nCLE) for gastric subepithelial lesions (SELs) on the diagnostic value is unclear. The study aimed to investigate the diagnostic efficacy of real-time nCLE for gastric SELs and to assess the technical aspects and safety of real-time nCLE. METHODS: Consecutive patients with gastric SELs ≥ 1 cm were prospectively investigated by endoscopic ultrasound (EUS), followed by nCLE. During EUS-nCLE, real-time nCLE diagnosis was made by an expert endoscopist. The procedure-relative adverse events were assessed and recorded. One-month washout period later, nCLE videos were reviewed off-line by the same endoscopist. The nCLE diagnoses were compared with corresponding pathological results. Additionally, image quality and interobserver agreements for the criteria were evaluated by three experienced endomicroscopists. RESULTS: Except for one failing to be punctured, 60 patients completed EUS-nCLE procedures successfully. Real-time nCLE had high diagnostic accuracies of ≥ 88.3% for gastric SELs. There were no significant differences between real-time and off-line nCLE diagnoses for gastric SELs (P > 0.05). The overall accuracy of real-time nCLE for diagnosis of gastric SELs was 86.7%. There were no procedure-relative adverse events occurred. In addition, the mean image quality score was 3.6 (1 = poor and 5 = excellent). The interobserver agreement was "almost perfect" for ectopic pancreas and "substantial" for gastrointestinal stromal tumor, leiomyoma, and carcinoma. CONCLUSIONS: Endoscopic ultrasound-nCLE could provide in vivo real-time diagnostic imaging with a high diagnostic accuracy. Meanwhile, real-time nCLE was feasible and had a satisfactory safety profile.

Chrysophanol Protects Against Acute Heart Failure by Inhibiting JNK1/2 Pathway in Rats.

BACKGROUND Acute heart failure (AHF) usually requires urgent therapy. Myocardial damage, oxidative stress, and inflammation are major components in the pathology of AHF. This study was designed to investigate the effects of chrysophanol on AHF. MATERIAL AND METHODS Sprague-Dawley rats were injected with isoprenaline hydrochloride to construct AHF rat models. AHF rats were treated with normal saline (negative control), chrysophanol, the combination of chrysophanol and SP600125, or benazepril (positive control) using sham rats as blank controls. Echocardiography, histological staining, and enzyme activity analysis were performed to assess the heart functions and myocardial damage. Effects on apoptosis, oxidative stress (OS), and inflammation were evaluated by biochemical analysis, TUNEL staining, and ELISA. RESULTS Chrysophanol improved the parameters of cardiac functions and alleviated the myocardial damage accompanied by the reduction of creatine kinase and lactate dehydrogenase activity. Meanwhile, chrysophanol inhibited the myocardial apoptosis along with the upregulation of Bcl-2 and downregulation of Bax and cleaved caspase-3. AHF-induced abnormal changes of OS parameters (MDA, GPx, CAT, SOD) and inflammatory markers (IL-6, IL-1ß, TNF-alpha, IFN-γ) were alleviated by chrysophanol. Benazepril treatment showed similar results with chrysophanol, while the addition of SP600125 enhanced the chrysophanol-mediated protection effects in AHF rats. Western blot analysis demonstrated that chrysophanol inhibited the phosphorylation of JNK1/2 and its upstream/downstream factors. CONCLUSIONS Chrysophanol improved cardiac functions and protected against myocardial damage, apoptosis, OS, and inflammation by inhibiting activation of the JNK1/2 pathway in AHF rat models. These finding indicate that chrysophanol may be a promising approach for treatment of AHF.

Endoscopic ultrasound-guided needle-based confocal laser endomicroscopy for diagnosis of gastric subepithelial tumors: a pilot study.

BACKGROUND: The diagnostic yield of current techniques for gastric subepithelial tumors (SETs) is suboptimal. This prospective study aimed to develop diagnostic criteria for needle-based confocal laser endomicroscopy (nCLE) of gastric SETs, and to evaluate the diagnostic efficacy, feasibility, and safety of endoscopic ultrasound-guided nCLE (EUS-nCLE). METHODS: Eligible patients were prospectively recruited to undergo EUS-nCLE. Four unblinded investigators evaluated nCLE videos and corresponding histopathology to develop the nCLE criteria. The recorded nCLE videos were reviewed off-line by one endoscopist 3 months later. Image quality (five-point scale, 1 = poor and 5 = very good) and the interobserver agreements were assessed. RESULTS: All 33 patients underwent successful EUS-nCLE procedures. The nCLE criteria for gastric SETs were established. Overall accuracy of off-line nCLE was significantly higher than that of EUS alone (87.9 % vs. 63.6 %; P = 0.02). The mean image quality score was 3.9. The kappa values of the interobserver agreements were 0.66 for gastrointestinal stromal tumor, 0.89 for ectopic pancreas, 0.58 for leiomyoma, and 0.72 for carcinoma. CONCLUSIONS: EUS-nCLE was feasible and safe to accurately diagnose gastric SETs.

Probe-based endomicroscopy for in vivo detection of gastric intestinal metaplasia and neoplasia: a multicenter randomized controlled trial.

Background and study aims Owing to the indistinctive endoscopic appearance of gastric intestinal metaplasia (GIM), gastric intraepithelial neoplasia (GIN), and early gastric cancer (EGC), a significant number of such lesions may be missed during surveillance endoscopy. The aim of this clinical trial was to assess the value of combined computed virtual chromoendoscopy (flexible spectral imaging color enhancement [FICE]) and probe-based confocal laser endomicroscopy (pCLE) for in vivo detection of GIM, GIN, and EGC. Patients and methods This was a multicenter, randomized controlled trial performed in 238 patients at four tertiary centers. Patients were randomized to FICE-guided pCLE with targeted biopsies (group A) or FICE with standard biopsies (group B). The diagnostic yield of GIM, GIN, or EGC was compared between the two groups. Results On a per-patient assessment, the diagnostic yield for GIM/GIN/EGC was 73.3 % (88/120) in group A and 63.6 % (75/118) in group B (P = 0.09). On a per-biopsy analysis, FICE-guided pCLE with targeted biopsies significantly increased the diagnostic yield of GIM/GIN/EGC vs. FICE with standard biopsies, from 31.5 % (252/800) to 75.1 % (313/417) (P < 0.001). In addition, pCLE-guided targeted biopsies led to a significant 48.5 % decrease in the number of biopsies per patient vs. FICE with standard biopsies (P < 0.001). Conclusions Real-time pCLE and targeted biopsies after FICE improved the diagnostic yield for the detection of GIM, GIN, and EGC, and only required about half the number of biopsies vs. FICE with standard biopsies. This may allow a better regimen for endoscopic surveillance and subsequent treatment of patients with premalignant and malignant gastric abnormalities.Trial registered at ClinicalTrials.gov (NCT02515721).

Anterior reduction and fusion for treatment of massive tear drop fracture of axis combining with inferior endplate serious traversed lesion: A retrospective study.

BACKGROUND: Tear drop fracture of axis represents a very small percentage of injuries of the cervical spine, but there is controversy about the treatment method for tear drop fracture of axis, especially when a large avulsed fragment is significant displacement, which combined with the inferior endplate serious traversed lesion of axis. OBJECTIVE: To evaluate the clinical outcome of anterior reduction, graft fusion of C2-3 and plate fixation in the management of massive tear drop fracture of axis combining with inferior endplate serious traversed lesion of axis. METHODS: There were 7 patients with a massive tear drop fracture of axis combining with inferior endplate serious traversed lesion. The avulsed ratio of inferior endplate of axis was 46.8 ± 13.4%, the average angle of rotation of the avulsed fragment was 30.4 ± 11.7, and the average displacement was 7.7 ± 2.8 mm. The posterior displacement of axis body was observed with three patients. All patients underwent anterior reduction, graft fusion of C2-3 and plate fixation with high anterior cervical retropharyngeal approach. The follow-up ranges from 2 years to 5 years. RESULTS: In all cases, tear drop fracture was reduced completely, avulsed fragment got bony healing, and bone graft achieved bony fusion at C2-3. There were no local angle deformity and rotated deformity in all patients, and there were normal physiological lordosis and good stabilization of upper cervical spine. The neurological function of one patient with American Spine Injury Association (ASIA) impairment scale type D was improved to type E postoperatively. Six patients without neurological lesion had no neurological syndrome after operation. CONCLUSIONS: Anterior surgical procedures would be an effective treatment of massive tear drop fracture of axis combining with inferior endplate serious traversed lesion. Complete reduction, sufficient stabilization and normal physiological lordosis of upper cervical spine could be achieved postoperatively.

A lower dose of fluorescein sodium is more suitable for confocal laser endomicroscopy: a feasibility study.

BACKGROUND AND AIMS: Image quality can be guaranteed with the conventional dosage of fluorescein sodium in probe-based confocal laser endomicroscopy (pCLE). However, yellow discoloration of the skin seriously affects daily life and simultaneously increases the risk of adverse events such as allergic reactions. The aim of this study was to test whether a lower dosage of fluorescein sodium can provide satisfactory image quality and to compare the diagnostic accuracy of gastric intestinal metaplasia (GIM) through a randomized blind controlled trial. METHODS: Consecutive patients were randomly assigned to different doses of fluorescein sodium. Image quality was determined by the endoscopists' subjective assessments and signal-to-noise ratio (SNR) assessment systems. Skin discoloration was tested using a neonatal transcutaneous jaundice detector. In addition, consecutive patients with a known or suspected diagnosis of GIM were examined by pCLE with the lower dose and the traditional dose. RESULTS: Only 0.01 mL/kg dose of 10% fluorescein sodium led to a significant decrease in image quality (P < .05), and a dose of 0.02 mL/kg had the highest SNR value (P < .05). There were no significant differences in skin discoloration between the 0.01 mL/kg and 0.02 mL/kg doses (P = .148) and no statistical difference in the diagnostic accuracy of pCLE for GIM between the 0.02 mL/kg and 0.10 mL/kg doses (P > .05). The kappa values for the correlation between pCLE and histopathology were 0.867 (95% confidence interval, 0.782-0.952) and 0.891 (95% confidence interval, 0.811-0.971). CONCLUSIONS: The 0.02 mL/kg dose of 10% fluorescein sodium seems to be the best dose for pCLE in the upper GI tract, with comparable image quality with the conventional dose and insignificant skin discoloration. This dose is also very efficient for the diagnosis of GIM.

New Classification of Gastric Pit Patterns and Vessel Architecture Using Probe-based Confocal Laser Endomicroscopy.

GOALS: To propose a new probe-based confocal laser endomicroscopy (pCLE) classification of gastric pit patterns and vessel architecture, and to assess the accuracy and interobserver agreement. BACKGROUND: pCLE is a newly developed endoscopic device that allows the application of laser microscopy with any conventional endoscope and mosaic imaging. STUDY: A total of 291 pCLE videos from 32 patients were recruited in phase I to establish the new pCLE image classification in the stomach. Eligible patients were then prospectively investigated by pCLE using the newly established classification system. All patients were examined first with high-definition endoscopy followed by pCLE at 7 standardized locations and endoscopic-suspected lesions. Targeted biopsies were performed with precise matching of pCLE recordings. RESULTS: The sensitivity and specificity of type 2b pit pattern for predicting atrophic gastritis were 88.51% and 99.19%, respectively. The sensitivity and specificity of type 2c pit pattern for predicting intestinal metaplasia were 92.34% and 99.34%, respectively. The overall sensitivity and specificity of type 3 pit pattern or vessel architecture for predicting neoplasia were 89.89% and 99.44%, respectively. The interobserver agreement was "substantial" (kappa=0.70) for the differentiation of neoplasia versus non-neoplasia. CONCLUSIONS: The new pCLE classification system in the stomach correlates well with specific pathologic conditions and is reproducible by multiple investigators. Multicenter researches are warranted to further validate its value in clinical practice.

Distinguishing characteristics of stem cells derived from different anatomical regions of human degenerated intervertebral discs.

INTRODUCTION: Several types of stem cells have been successfully demonstrated to exist in the human degenerated intervertebral disc (IVD), which is composed of annulus fibrosus (AF), nucleus pulposus (NP) and cartilage endplate (CEP). However, the differences in the biological characteristics among these and bone marrow derived mesenchymal stem cells (BM-MSCs) remain unclear. MATERIALS AND METHODS: To investigate this issue, cells were harvested from human AF, NP, CEP, and bone marrow, respectively; passage 2 cells were selected using the agarose suspension culture system to obtain stem cell clones. Following expansion in vitro, stem cells from different anatomical regions were compared regarding the morphology, proliferation ability, immunophenotypic expression, and multi-lineage differentiation capacity. In addition, stem cell-alginate bead compositions were constructed for the comparison of DNA and sGAG content. RESULTS: There were subtle differences regarding cell morphology, but no significant differences in proliferation ability among the four types of stem cells. For the immunophenotypic analysis, all stem cells basically fulfilled the criteria for mesenchymal stem cells (MSCs), which have been published by the International Society for Cellular Therapy (ISCT), with a significant difference in CD105 expression. A comparison of the osteogenic capacities indicated: cartilage endplate-derived stem cells (CESCs) > annulus fibrosus-derived stem cells (AFSCs) > BM-MSCs > nucleus pulposus-derived stem cells (NPSCs). The chondrogenesis difference was similar to osteogenesis. For adipogenesis: BM-MSCs >NPSCs >CESCs >AFSCs. In the stem cell/alginate composition, the CESCs consistently showed the superior chondrogenic potential among all those cell types. CONCLUSIONS: Our data indicated that all the four types of stem cells shared some similar biological properties (regarding shape, proliferation ability and immunophenotypic expression). CESCs, which had the strongest osteogenic and chondrogenic potentials, may serve as excellent seed cells for NP/cartilage or bone tissue engineering.

[Study on Anti-Inflammatory and Analgesic Effects of Different Processing Products of Strychnos nux-vomica Seeds].

Objective: To study the differences of anti-inflammatory and analgesic effects between oil,sand and vinegar processing Strychnos nux-vomica seeds. Methods: Mouse auricular swelling and writhing test and mice hot water tail flick latency effect method were used to study and compare the anti-inflammatory and analgesic effects of different processing products of Strychnos nux-vomica seeds. Results: The anti-inflammatory and analgesic effects of vinegar processing Strychnos nux-vomica seeds was better than that of oil and sand processing products. Conclusion: This study can provide theoretical basis for the optimization of processing technology of reducing toxicity and enhancing effects of processed Strychnos nux-vomica seeds.

Blood donation in China: sustaining efforts and challenges in achieving safety and availability.

China has entered a new phase in blood safety and availability through persistent efforts in the past decades. Based on national data from 2008 to 2012, we present a comprehensive review on the blood services ranging from policy and organization, supply, donors, screening and processing, and clinical use to government response in contemporary China. Current evidence suggests that the Chinese blood industries, after continual efforts in reforms on the legal framework and national management system, have been in a relatively steady but bottleneck stage. Although the blood industries have had an impressive track record on management and resolving problems, such as low availability, limited donors, deficient laboratory tests, shortage of blood products, and unnecessary clinical usage of blood still exist nationwide. While medical technology and services have seen a rapid increase in progress in recent years, they have not coordinated with the development of the national health care system. This article presents an analysis with detailed data, rich contents, and recent response from the Chinese government, allowing readers to appreciate how China, a country with more than 19.13% of the world's population, has long endeavored to improve safety and availability of blood. Meantime, the article sincerely welcomes the guidance on policymaking and technical assistance from the international community. Data in this article do not include those of Hong Kong, Macao, or Taiwan.

Diagnostic value of probe-based confocal laser endomicroscopy and high-definition virtual chromoendoscopy in early esophageal squamous neoplasia.

BACKGROUND: Detection and differentiation of esophageal squamous neoplasia (ESN) are of value in improving patient outcomes. Probe-based confocal laser endomicroscopy (pCLE) can serve in targeted biopsies in the diagnosis of GI neoplasia. However, its performance in ESN has not yet been reported. OBJECTIVE: To investigate the diagnostic value of pCLE for early ESN screened by high-definition virtual chromoendoscopy (I-Scan) and verified by Lugol chromoendoscopy and histopathology. DESIGN: Prospective and noninferiority trial. SETTING: Single center in China. PATIENTS: Patients were enrolled who (1) previously had histologically verified early ESN or (2) were about to undergo screening endoscopy and were 50 to 80 years of age between February 2013 and February 2014. INTERVENTIONS: The esophagus was investigated sequentially by white-light endoscopy, I-Scan, then pCLE and iodine chromoendoscopy. The results were interpreted and compared with histopathologic results. MAIN OUTCOME MEASUREMENTS: Diagnostic characteristics of pCLE and I-Scan. RESULTS: In total, 356 patients were enrolled. In all, 42 patients were histologically proven to have 47 neoplasias. The diagnostic value of pCLE for ESN during ongoing endoscopy has a sensitivity, specificity, and accuracy of 94.6%, 90.7%, and 92.3%, respectively. The interobserver and intraobserver agreement was good and excellent, with κ values of 0.699 and 0.895, respectively. The detection rate by using I-Scan and Lugol chromoendoscopy was 10.4% and 12.9%, respectively (P<.01 for noninferiority). LIMITATIONS: Single center. CONCLUSIONS: pCLE shows promise in diagnosing and differentiating ESN in vivo. The screening performance of I-Scan in the detection of ESN is noninferior to that of iodine chromoendoscopy.

Vertebroplasty versus kyphoplasty in osteoporotic vertebral compression fracture: a meta-analysis of prospective comparative studies.

PURPOSE: The goal of this article is to evaluate the efficacy and the safety of the percutaneous vertebroplasty (PVP) versus percutaneous kyphoplasty (PKP) in dealing with the osteoporotic vertebral compression fracture (OVCF). METHODS: In July 2014, a comprehensive systematic computer-based online search was performed by using the databases of PubMed, EMBASE, Cochrane Library, Web of Science, Wan Fang, and the China Biological Medicine. Only prospective comparative trials (PCT) and randomized controlled trials (RCT) that compared PVP with PKP were included. Trials were screened based on the inclusion and exclusion criteria previously formed. The Cochrane collaboration guidelines were also used to assess the quality of these included studies. The primary data of these studies [volume of the cement, postoperative vertebral height, visual analog scale (VAS) score and Oswestry Disability Index (ODI) score after the surgery, and so on] were carefully abstracted and processed by Revman 5.2.0 software The publication bias of the main results (cement leakage and adjacent-level fracture) were examined by Stata 12.0 (Begg and Egger test). Furthermore, the stability of the main results were also detected by sensitivity and cumulative analyses. RESULTS: Six RCT and 14 PCT studies involving 1,429 patients met our criteria and were included finally. Comparing these two methods, the PKP group took more operation time [SMD = 0.66, 95 % CI (0.28, 1.03), p = 0.0006] with higher anterior vertebral body height [SMD = 1.40, 95 % CI (0.49, 2.32), p = 0.003], greatly reduced Cobb angle in the long run [SMD = -0.61, 95 % CI (-1.04, -0.19), p = 0.005] and had lower risk of cement leakage. However, in VAS scores and ODI scores after the surgery whether for the short-term efficacy (no more than 1 week after the surgery) or long-term efficacy (more than six months), Cobb angle in the short run and new fracture in the adjacent level, no statistically differences were found between the two groups. CONCLUSIONS: Based on current evidence, PVP takes less time in the operation, while it has greater risk of cement leakage, was inferior in reducing Cobb angle in the long term and results in lower anterior vertebral body height after the surgery. For pain relief, which is the main desire of the patients, both procedures provide significant improvement in VAS and ODI pain scores. PVP is still an effective procedure.