New Insights into the Role of Oral Microbiota Dysbiosis in the Pathogenesis of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a group of chronic intestinal inflammatory disorders with a prolonged duration characterized by recurrent relapse and remission. The exact etiology of IBD remains poorly understood despite the identification of relevant risk factors, including individual genetic susceptibility, environmental triggers, and disruption of immune homeostasis. Dysbiosis of the gut microbiota is believed to exacerbate the progression of IBD. Recently, increasing evidence has also linked oral microbiota dysbiosis with the development of IBD. On the one hand, IBD patients show significantly unbalanced composition and function of the oral microbiota known as dysbiosis. On the other, overabundances of oral commensal bacteria with opportunistic pathogenicity have been found in the gut microbiota of IBD patients. Herein, we review the current information on the causative factors of IBD, especially recent evidence of IBD-associated oral microbiota dysbiosis, which has seldom been covered in the previous literature review, highlighting the pathogenic mechanisms of specific oral bacteria in the development of IBD. Ectopic colonization of several oral bacteria, including a subset of Porphyromonas gingivalis, Streptococcus mutans, Fusobacterium nucleatum, Campylobacter concisus, and Klebsiella pneumoniae, may lead to destruction of the intestinal epithelial barrier, excessive secretion of inflammatory cytokines, disruption of the host immune system, and dysbiosis of gut microbiota, consequently aggravating chronic intestinal inflammation. Studying oral microbiota dysbiosis may open future horizons for understanding IBD pathogenesis and provide novel biomarkers for IBD. This review also presents the current treatment and new perspectives for IBD treatment.

Sinus tarsi approach versus the extended lateral approach for displaced intra-articular calcaneal fractures: a systematic review and meta-analysis.

BACKGROUND: The goal of this study was to review eligible randomized controlled trials to determine the efficacy of the sinus tarsi approach (STA) versus the extended lateral approach (ELA) for the treatment of displaced intra-articular calcaneal fractures (DIACF). METHODS: Using appropriate keywords, we identified relevant studies using PubMed, the Cochrane Library, Embase, CNKI, VANFUN, and VIP. Key pertinent sources in the literature were also reviewed, and all articles published through June 2020 were considered for inclusion. For each study, we assessed odds ratios (ORs), mean difference (MD), and 95% confidence interval (95% CI) to assess and synthesize the outcomes. RESULTS: We included 15 RCTs, with a total of 847 patients in the STA group and 959 in the ELA group. The results found that after STA and ELA, no significant difference in changes of Böhler's angle (WMD: 0.746, 95% CI: - 0.316-1.809), Gissane angle (WMD: - 0.710, 95% CI: - 2.157-0.737), calcaneal heights (WMD: 0.378, 95% CI: - 1.973-2.728), calcaneal widths (SMD: - 0.431, 95% CI: - 1.604- 0.742), calcaneal lengths (WMD: 0.691, 95% CI: - 0.749-2.131). Besides, there was no significant difference in the incidence of complications between the STA group and the ELA group (RR: 0.592, 95% CI: 0.336-1.045). CONCLUSION: There was no difference in clinical efficacy between STA and ELA in treating DIACF. Besides, there is still a need of large-sample, high-quality, long-term randomized controlled trials to confirm the conclusion. LEVEL OF EVIDENCE: Level I-High-Quality Prospective Randomized Study.

[Influence of different processing methods on Lonicerae Japonicae Flos from Donghai cultivation base in Jiangsu province].

To study the impact of five different origin processing methods, namely natural drying, drying in baking shop, drying by microwave heating, drying in drum and drying with sulphur fumigation, on the quality of Lonicerae Japonicae Flos from Donghai cultivation base in Jiangsu Province, with the contents of chlorogenic acid and galuteolin and the similarity in HPLC fingerprints as the evaluation indicators. The results showed that different origin processing methods had significant impact on the content of chlorogenic acid and the similarity in HPLC fingerprints, but with no significant difference on the content of galuteolin. By means of drying by microwave heating and drying in drum, the samples showed higher contents of chlorogenic acid, respectively 3.67% and 3.39%. The similarities of HPLC fingerprints were 0.815 and 0.793, respectively. By means of the drying in baking shop and the drying with sulphur fumigation, the contents of chlorogenic acid in the samples were 2. 87% and 2. 53% , respectively. The similarities of HPLC fingerprints were 0.964 and 0.765, respectively. The lowest content of chlorogenic acid in naturally dried samples was 1.92%. The similarity of HPLC fingerprints was 0.940. According to the findings as well as the internal control standards for Lonicerae Japonicae Flos herbs of Jiangsu Kanion Pharmaceutical Co. , Ltd. , the optimum processing method for Lonicerae Japonicae Flos from Donghai cultivation base was the drying in baking shop. This study provided a theoretical basis for determining the processing method for Lonicerae Japonicae Flos from Donghai cultivation base of Jiangsu Province.

Identifying optimal surgical approach among T1N2-3M0 non-small cell lung cancer patients: a population-based analysis.

Background: Whether stage T1N2-3M0 non-small cell lung cancer (NSCLC) patients could benefit from surgery and the optimal surgical procedure have remained controversial and unclear. This study aimed to investigate whether stage T1N2-3M0 NSCLC can benefit from different surgery types and develop a tool for survival prediction. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients diagnosed with stage T1N2-3M0 NSCLC between 2000 and 2015. A 1:1 propensity score-matched (PSM) analysis was used to balance the distribution of clinical characteristics. Survival analyses were performed by using the Kaplan-Meier (KM) curves and Cox proportional hazards regression. All patients were randomly split at a ratio of 7:3 into training and validation cohorts. The nomogram was constructed by integrating all independent predictors for overall survival (OS) and cancer-specific survival (CSS). The model's performance was evaluated by discrimination, calibration ability, and risk stratification ability. Results: A total of 4,671 patients were enrolled. After 1:1 PSM, the distribution proportions of clinical characteristics in 1,146 patients were balanced (all P>0.05). The non-surgical approach was associated with worse survival compared with sublobectomy and lobectomy in the unmatched and matched cohorts. The multivariate Cox analysis showed that sublobectomy and lobectomy were both related to better OS and CSS rates compared with no surgery (P<0.001). Moreover, the results of subgroup analyses based on age, N stage, and radiotherapy or chemotherapy strategy were consistent. A total of 801 patients were included in the training cohort and 345 cases constituted the validation cohort. The nomogram constructed for the 1-, 3-, and 5-year OS and CSS prediction showed good discrimination, performance, and calibration both in the training and validation sets. Significant distinctions in survival curves between different risk groups stratified by prognostic scores were also observed (all P<0.001). Conclusions: Stage T1N2-3M0 NSCLC patients could benefit from sublobectomy or lobectomy, and lobectomy provides better survival benefits. We developed and validated nomograms, which could offer clinicians instructions for strategy making.

Anatomy of large animal spines and its comparison to the human spine: a systematic review.

Animal models have been commonly used for in vivo and in vitro spinal research. However, the extent to which animal models resemble the human spine has not been well known. We conducted a systematic review to compare the morphometric features of vertebrae between human and animal species, so as to give some suggestions on how to choose an appropriate animal model in spine research. A literature search of all English language peer-reviewed publications was conducted using PubMed, OVID, Springer and Elsevier (Science Direct) for the years 1980-2008. Two reviewers extracted data on the anatomy of large animal spines from the identified articles. Each anatomical study of animals had to include at least three vertebral levels. The anatomical data from all animal studies were compared with the existing data of the human spine in the literature. Of the papers retrieved, seven were included in the review. The animals in the studies involved baboon, sheep, porcine, calf and deer. Distinct anatomical differences of vertebrae were found between the human and each large animal spine. In cervical region, spines of the baboon and human are more similar as compared to other animals. In thoracic and lumbar regions, the mean pedicle height of all animals was greater than the human pedicles. There was similar mean pedicle width between animal and the human specimens, except in thoracic segments of sheep. The human spinal canal was wider and deeper in the anteroposterior plane than any of the animals. The mean human vertebral body width and depth were greater than that of the animals except in upper thoracic segments of the deer. However, the mean vertebral body height was lower than that of all animals. This paper provides a comprehensive review to compare vertebrae geometries of experimental animal models to the human vertebrae, and will help for choosing animal model in vivo and in vitro spine research. When the animal selected for spine research, the structural similarities and differences found in the animal studies must be kept in mind.

Metformin Improves Functional Recovery After Spinal Cord Injury via Autophagy Flux Stimulation.

Spinal cord injury (SCI) is a severe neurological disease with few efficacious drugs. Autophagy is a cellular process to confront with stress after SCI and considered to be a therapeutic target of SCI. In this study, we investigated the therapeutic effect of metformin on functional recovery after SCI and its underlying mechanism of autophagy regulation. Using a rat model of traumatic SCI, we found improved function recovery which was paralleled by a reduction of apoptosis after metformin treatment. We further examined autophagy via detecting autophagosomes by transmission electron microscopy and immunofluorescence, as well as autophagy markers by western blot in each groups. The results showed that the number of autophagosomes and expression of autophagy markers such as LC3 and beclin1 were increased in SCI group, while autophagy substrate protein p62 as well as ubiquitinated proteins were found to accumulate in SCI group, indicating an impaired autophagy flux in SCI. But, metformin treatment attenuated the accumulation of p62 and ubiquitinated proteins, suggesting a stimulative effect of autophagy flux by metformin. Blockage of autophagy flux by chloroquine partially abolished the apoptosis inhibition and functional recovery effect of metformin on SCI, which suggested that the protective effect of metformin on SCI was through autophagy flux stimulation. Activation of AMPK as well as inhibition of its downstream mTOR signaling were detected under metformin treatment in vivo and in vitro; inhibition of AMPK signaling by compound C suppressed autophagy flux induced by metformin in vitro, indicating that AMPK signaling was involved in the effect of metformin on autophagy flux regulation. Together, these results illustrated that metformin improved functional recovery effect through autophagy flux stimulation and implied metformin to be a potential drug for SCI therapy.

Role of dual energy X-ray absorptiometry in monitoring fracture healing in a rat femoral fracture model.

OBJECTIVE: To dynamically monitor the bone mineral density (BMD) and the histomorphological changes during fracture healing in a rat femoral fracture model and to explore the role of dual energy X-ray absorptiometry (DEXA) in evaluating bone fracture healing. METHODS: Sixty three-month-old female Sprague Dawley rats were used to establish right femoral fracture models. The BMD of the callus of the fractured right femur were scanned by DEXA at 2, 4, 6, 8, 10 and 12 weeks after operation, respectively. A light microscope was used to evaluate the callus of each rat at the same time. The corresponding segment of the left femur was taken as a control. RESULTS: The BMD at the fractured site increased significantly during the process of fracture healing, which shows an obvious healing trend. The callus BMDs were 29.5%, 48.3%, 85.3%, and 105.2% of the BMD of the control limb at 2, 4, 6 and 8 weeks after fracture, respectively. There was a significantly difference between the groups. A compatibility on time was found between the BMD and the histomorphological characteristics at the fractured site during the process of fracture healing. The fracture healing was almost completed at 8 weeks after fracture as assessed by its histomorphological characteristics when the callus BMD reached to 105.2% of the BMD of the control limb. The BMD of the distal metaphysis decreased until 12 weeks after fracture. CONCLUSIONS: DEXA can evaluate the mineralization of the callus during the fracture healing process accurately and quantitatively and is more sensitive than plain radiography in detecting impaired bone unions, which indicates that it may play an important role in monitoring fracture healing.

[Minimal invasive elastic intramedullary nails and external fixation for treatment of comminuted closed fracture of tibia-fibula shaft].

OBJECTIVE: To investigate the clinical results of external fixation and AO titanium elastic intramedullary nailing for treatment of tibia-fibula comminuted closed fractures. METHODS: From June 2010 to June 2012,58 patients with tibia-fibula comminuted closed fractures were treated with external fixation and AO titanium elastic intramedullary nailing, including 31 males and 27 females with an average age of 38.5 years old ranging from 21 to 57 years old. According to the system of AO Classification, the fractures were classified as type B1 in 9 cases,type B2 in 7 cases, type B3 in 10 cases, type Cl in 14 cases, type C2 in 12 cases,and type C3 in 6 cases. According to the system of Winquist-Hanson,the fractures' comminuted were classified as grade 1 in 23 cases, grade 2 in 17 cases, grade 3 in 12 cases, and grade 4 in 6 cases. According to the system of Johner-Wruhs, clinical results were compared between different type and grade groups by the time of last followed-up. RESULTS: All 58 patients were followed up with an average time of 6.8 months (ranged from 18 to 36 weeks). All fractures had clinical healing with an average time of 28 weeks (ranged from 24 to 32 weeks). The total rate of good to excellent results was 91.4%. The rate of good to excellent in the group of grade 1 was higher than that of other grades. The complication rates and fracture healing time would increase respectively with higher Winquist-Hanson's grade. The complication rates in the group of type C3 was higher than that of other types, but the rate of good to excellent was lower than that of other types. The complication rates in the group of type B1 was lower than that of other types,but the rate of good to excellent was higher than that of other types. CONCLUSION: Minimal invasiveusing AO titanium elastic intramedullary nailing combined with external fixation for treatment of tibia-fibula fractures especially for the multiple-segment,long spiral mild-to-moderate comminuted with hidden fracture can get satisfactory reduction and reliable fixation,it conformes to the principle of BO completely, protects the fracture end blood supply,reduces the external fixation time, has less skin soft tissue complications, postoperative function recovered satisfactorily.

Stimulation of autophagy promotes functional recovery in diabetic rats with spinal cord injury.

In this study we examined the relationship between autophagy and apoptosis in diabetic rats after spinal cord injury (SCI), also we determined the role of autophagy in diabetes-aggravated neurological injury in vivo and in vitro. Our results showed that diabetes decreased the survival of neurons, promoted astrocytes proliferation, increased inflammatory cells infiltration and inhibited functional recovery after SCI. Diabetes was shown to confer increased activation of apoptotic pathways, along with an increase in autophagy; similar effects were also observed in vitro in neuronal PC12 cells. Treatment with rapamycin, an autophagy activator, partially abolished the adverse effect of diabetes, suggesting that diabetes may enhance neurological damage and suppress locomotor recovery after SCI, in addition to its effects on apoptosis and autophagy. In contrast, further stimulation of autophagy improved neurological function via inhibition of apoptosis. These results explained how diabetes exacerbates SCI in cellular level and suggested autophagy stimulation to be a new therapeutic strategy for diabetic SCI.

[Clinical effects of surgical vs manual reduction of ankle fractures].

OBJECTIVE: To investigate the clinical effects of surgical vs manual reduction of ankle fractures. METHODS: From March 2006 to April 2010,301 patients with ankle fractures were analyzed retrospectively, of whom 134 patients were treated by manual reduction and plaster fixation, and the other 167 patients underwent surgical treatment. In manual reduction group, there were 86 males and 48 females with a mean age of (38.2 +/- 15.7) years, involving Weber-Denis A in 55 cases,Weber-Denis B in 60 cases, and Weber-Denis C in 19 cases. In surgical reduction group, there were 115 males and 52 females with a mean age of (39.6 +/- 11.9) years, involving Weber-Denis A in 59 cases, Weber-Denis B in 52 cases and Weber-Denis C in 56 cases. The score of the ankle's symptoms and function was calculated according to Mazur,and the difference was analyzed by Chi-squire test. RESULTS: Of the 114 patients with Weber-Denis A, 55 patients were in manual reduction group, with excellent, good, acceptable and poor results in 18, 20, 11 and 6 patients respectively vs 26, 25, 6 and 2 in surgical reduction group of 59 patients. In patients with Weber-Denis B, there were 60 patients in manual reduction group, with excellent, good, acceptable and poor results in 20 , 26, 8 and 6 patients vs 25, 21, 5, and 1 in surgical reduction group of 52 patients. There was no significant difference in clinical effects between the two group of Weber-Denis A and B. The remaining 75 patients belonged to Weber-Denis C, of whom 19 patients were in manual reduction group,with excellent, good, acceptable and poor results in 2, 3, 7 and 7 patients vs 21, 18, 11 and 6 in surgical reduction group of 56 patients. There was no significant difference in clinical effects between the two groups of Weber-Denis C (P=0.007). CONCLUSION: The clinical effect of surgical reduction group was obviously better than that of manual reduction group for Weber-Denis C, and therefore surgical intervention is recommended for this type of fracture.

[Biomechanical comparison of Evans procedure and Chrisman-Snook technique for the treatment of II degree lateral collateral ligament of ankle joint].

OBJECTIVE: To measure the stability of Evans procedure and Chrisman-Snook technique in the treatment of II degree lateral collateral ligament of ankle joint, and provide basis for treatment and prognosis. METHODS: From July 2008 to June 2009,18 frozen corpes were collected, including 10 males and 8 females, with an average age of fresh 39.3 +/- 11.2 years. The frozen corpes were randomly divided into three group, including normal controls(group A), Evans procedure (group B) and Chrisman-Snook technique ( group C), 6 specimens in each group. Anterior talofibular ligament and calcaneofibular ligament were cut off to cause II degree lateral collateral ligament in group B and C. Evans procedure or Chrisman-Snook technique were applied to restore lateral collateral ligament, and measure biomechnics. The displacement of tibiotalar joint and subtalar joint were observed. RESULTS: (1) The lateral stress results of tibiotalar joint showed the displacement by Evans procedure (group B) was greater than other groups (P < 0.0001). There were no significant differences between group A and C (P > 0.05). (2) The lateral stress results of subtalar joint showed the displacement by Evans procedure (group B) was greater than other groups (P< 0.0001). There were no significant differences between group A and C (P > 0.05). CONCLUSION: Ankle instability is caused by ankle joint lateral collateral ligament injury. Chrisman-Snook technique is better than Evans procedure in stability on the early stage of ankle joint restoration, and conform to principle of biomechanics.

[Effect of erythromycin on apoptosis of epithelial cell in nasal polyps].

OBJECTIVE: To study the effect of erythromycin on apoptosis and expression of Bax and Bcl-2 of epithelial cell in nasal polyps. METHODS: Epithelial cells from thirty nasal polyps and fifteen inferior turbinates were cultured in Dulbecco Eagle and Ham F12 (1:1) and divided into two groups (one group were treated with Erythromycin). Apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling and expression of Bcl-2 and Bax detected by immunohistochemistry at 1, 3, 5 days after culture. RESULTS: The apoptosis indexes (AI) of epithelial cell in nasal polyps after cultured for 1, 3, 5 days with erythromycin were (33.23 +/- 6.50)%, (38.21 +/- 7.22)% and (52.63 +/- 7.86)% respectively. The AI of epithelial cell in inferior turbinates were (31.02 +/- 5.60)%, (32.13 +/- 7.15)% and (39.64 +/- 7.48)% respectively. There was significant difference between two groups at 5 day after culture (P < 0.05). Expression of Bax and Bcl-2 of epithelial cell was significantly higher in nasal polyps than that in inferior turbinates (P < 0.01). Expression of Bax of epithelial cell cultured with erythromycin was significantly higher than that in the controls (P < 0.05). Apoptosis was clearly promoted after 5 day culture with Erythromycin (P < 0.05). CONCLUSIONS: Erythromycin promoted expression of Bax and apoptosis of epithelial cell in nasal polyps.