[A cone-beam computed tomography evaluation of three-dimensional changes of circummaxillary sutures following maxillary protraction with alternate rapid palatal expansions and constrictions].

OBJECTIVE: To assess three-dimensional (3D) changes of circummaxillary sutures following maxillary protraction with alternate rapid palatal expansions and constrictions (RPE/C) facemask protocol in maxillary retrusive children, and to investigate the relationship between the changes of circum-maxillary sutures and zygomaticomaxillary suture (ZMS) maturation, and to explore the factors of maxilla forward movement with RPE/C and facemask. METHODS: In the study (clinical trial registration No: ChiCTR2000034909), 36 maxillary retrusive patients were recruited and block randomized to either the rapid palatal expansion (RPE) group or the RPE/C group. Patients aged 7 to 13 years, Class Ⅲ malocclusion, anterior crossbite, ANB less than 0°, Wits appraisal less than -2 mm, and A-Np less than 0 mm were included in the study. The RPE group received rapid palatal expansion, whereas the RPE/C group received alternate rapid palatal expansions and constrictions, and both with facemask protraction. Head orientations of cone-beam computed tomography (CBCT) images were implemented by Dolphin 11.7. 3D measurements of circummaxillary sutures on CBCT images were evaluated using Mimics 10.01 before (T0) and after treatment (T1). The changes were analyzed with independent t test, two-way ANOVA, Pearson correlation and regression analysis. RESULTS: Two subjects in the RPE/C group were lost to follow-up. A total of 34 patients reached the completion criteria and were analyzed. Compared with the RPE group, sagittal changes of circummaxillary sutures were significantly increased in the RPE/C group with 1.21 mm advancement of zygomaticotemporal suture, 2.20 mm of ZMS, 1.43 mm of zygoma-ticofrontal suture (P < 0.05, respectively). Except for the zygomaticotemporal suture, the rest forward sagittal changes of other circummaxillary sutures showed no major difference in terms of the ZMS maturation. The Spearman's correlation in RPE/C indicated a strong positive correlation of sagittal changes between ZMS and point A (P < 0.01) with a regression analysis R2=42.5%. CONCLUSION: RPE/C might be more effective on the treatment of maxillary retrusive children. As one of the major mechanical loading sutures during orthopedic therapy, ZMS showed a strong positive correlation with point A on sagittal changes.

Unusual severe gastritis and gastric ulcers caused by pembrolizumab.

Pembrolizumab (an immune checkpoint inhibitor)-related gastritis and gastric ulcers are rare immune-related adverse events, which are insufficiently treated with proton pump inhibitors (PPIs) therapy alone, and usually require systemic steroid therapy and even other biological agents (such as infliximab) in severe cases. Here, we report a case of 49-years-old woman suffering from gastritis and gastric ulcers after pembrolizumab treatment, which was refractory to 2 months of PPI therapy. The diagnosis was made by the clinical and histopathologic presentations. She had immediate resolution of abdominal symptoms after initiation of steroid treatment, but the gastritis and gastric ulcers improved slowly and lasted for months as shown in endoscopy. She was finally treated with extended steroid therapy without serious complications. We discuss the latest treatment options and our management strategies of the case.

Decoding molecular mechanism underlying binding of drugs to HIV-1 protease with molecular dynamics simulations and MM-GBSA calculations.

HIV-1 protease (PR) is thought to be efficient targets of anti-AIDS drug design. Molecular dynamics (MD) simulations and multiple post-processing analysis technologies were applied to decipher molecular mechanism underlying binding of three drugs Lopinavir (LPV), Nelfinavir (NFV) and Atazanavir (ATV) to the PR. Binding free energies calculated by molecular mechanics generalized Born surface area (MM-GBSA) suggest that compensation between binding enthalpy and entropy plays a vital role in binding of drugs to PR. Dynamics analyses show that binding of LPV, NFV and ATV highly affects structural flexibility, motion modes and dynamics behaviour of the PR, especially for two flaps. Computational alanine scanning and interaction network analysis verify that although three drugs have structural difference, they share similar binding modes to the PR and common interaction clusters with the PR. The current findings also confirm that residues located interaction clusters, such as Asp25/Asp25', Gly27/Gly27', Ala28/Ala28', Asp29, Ile47/Ile47', Gly49/Gly49', Ile50/Ile50', Val82/Val82' and Ile84/Ile84, can be used as efficient targets of clinically available inhibitors towards the PR.

Insights into effect of the Asp25/Asp25' protonation states on binding of inhibitors Amprenavir and MKP97 to HIV-1 protease using molecular dynamics simulations and MM-GBSA calculations.

The protonation states of two aspartic acids in the catalytic strands of HIV-1 protease (PR) remarkably affect bindings of inhibitors to PR. It is requisite for the design of potent inhibitors towards PR to investigate the influences of Asp25/Asp25' protonated states on dynamics behaviour of PR and binding mechanism of inhibitors to PR. In this work, molecular dynamics (MD) simulations, MM-GBSA method and principal component (PC) analysis were coupled to explore the effect of Asp25/Asp25' protonation states on conformational changes of PR and bindings of Amprenavir and MKP97 to PR. The results show that the Asp25/Asp25' protonation states exert different impacts on structural fluctuations, flexibility and motion modes of PR. Dynamics analysis verifies that Asp25/Asp25' protonated states highly affect conformational dynamics of two flaps in PR. The binding free energy calculations results suggest that the Asp25/Asp25' protonated states obviously strengthen bindings of inhibitors to PR compared to the non-protonation state. Calculations of residue-based free energy decomposition indicate that the Asp25/Asp25' protonation not only disturbs the interaction network of inhibitors with PR but also stabilizes bindings of inhibitors to PR by cancelling the electrostatic repulsive interaction. Therefore, special attentions should be paid to the Asp25/Asp25' protonation in the design of potent inhibitors towards PR.

[Laparoscopic diagnosis of postoperative recurrence of peritoneal metastasis in gastric cancer patients and the clinical efficacy of bidirectional intraperitoneal and systemic chemotherapy].

Objective: To explore the diagnostic value of laparoscopy in the postoperative recurrence of peritoneal metastasis in gastric cancer, and to investigate the efficacy of bidirectional intraperitoneal and systemic (BIPS) chemotherapy for the recurrence. Methods: The descriptive case series study was conducted. Case inclusion criteria: (1) gastric cancer patients without synchronous distant metastasis received D2 radical gastrectomy; (2) postoperative adjuvant chemotherapy was administered; (3) no other distant metastasis except recurrence of peritoneal metastasis; (4) age of 18-75 years; (5) Eastern Cooperative Oncology Group (ECOG) performance-status score≤2; (6) pretreatment evaluation suggested that surgery and chemotherapy could be tolerated. Eight consecutive gastric cancer patients with postoperative recurrence of peritoneal metastasis who met the above criteria at Department of Gastrointestinal Surgery of Ruijin Hospital from September 2015 to September 2016 were enrolled into the study. There were 6 males and 2 females with the median age of 52 (38-68) years. They received laparoscopy or laparotomy first, and then were evaluated with reference to the Sugarbaker peritoneal cancer index (PCI) and the peritoneal metastasis classification of gastric cancer developed by the Japanese Gastric Cancer Research Association. A peritoneal access port was implanted in the subcutaneous space of the lower abdomen and the patients received chemotherapy for 21 days as a course of treatment. All the patients received intraperitoneal 20 mg/m(2) of paclitaxel (PTX) via implanted subcutaneous peritoneal access ports and intravenous 50 mg/m(2) of PTX at day 1 and day 8, meanwhile 80 mg/m(2) of Tigio was orally administered per day for 14 consecutive days, followed by 7 days of interval. Follow-up ended on December 15, 2019. Results: Of these 8 patients with recurrence of peritoneal metastasis after gastric cancer surgery, 1 case underwent laparotomy and loop stoma of terminal ileum because of complete colonic obstruction, and the remaining 7 cases underwent laparoscopy successfully and the recurrence of peritoneal metastasis was clearly diagnosed. Two patients with ovarian metastasis underwent laparoscopic bilateral adnexectomy. The median follow-up time was 17.5 (1.5 to 39.0) months, the median number of BIPS chemotherapy course was 11 (1 to 30), and the median survival time (MST) after BIPS chemotherapy was 17.0 months. The major adverse reaction in BIPS treatment was mainly myelosuppression, of which grade 3/4 leukopenia and neutropenia developed in 1 and 2 cases respectively. No BIPS-related death occurred. The MST of gastric cancer after radical gastrectomy was 40.0 months. Conclusions: Laparoscopy is a safe and feasible method for diagnosing the recurrence of peritoneal metastasis of gastric cancer. BIPS chemotherapy is effective and safe for its treatment and deserves further study.

[Clinical and genetic characteristics of children with STXBP1 encephalopathy].

Objective: To investigate the clinical and genetic characteristics of developmental and epileptic encephalopathy (DEE) caused by syntaxin-binding protein 1 (STXBP1) gene mutation. Methods: The clinical data, gene variation and treatment outcome of 15 children with STXBP1 encephalopathy admitted to Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2014 to June 2019 were analyzed retrospectively. Results: Among 15 patients, 11 were male and 4 were female, age ranged from 2 months to 69 months. The clinical manifestations of 14 children were epilepsy and developmental delay (DD) and the remaining one showed developmental delay without seizure. The onset age of epilepsy ranged from two days to 19 months and 11 of them experienced the first attack before 1 year of age. The common seizure types were epileptic spasms and tonic seizures. Seven patients were diagnosed with Ohtahara syndrome or West syndrome. Epileptic form discharges were observed in the interictal electroencephalograms (EEG) of 11 patients, including multifocal discharges, suppression-burst and hypsarrhythmia. The brain magnetic resonance imaging of 7 children were abnormal, including myelin dysplasia, less white matter, lack of corpus callosum or hypoplasia. The follow-up time ranged from 2 months to 57 months, after the last follow-up, 3 cases were seizure free, 6 children showed partial response and the other 5 patients had no response on multitherapy. Six of 8 patients showed good responses to levetiracetam (LEV) monotherapy or in combination with other antiepileptic drugs (AEDs). Vigabatrin (VGB) was applied to 5 patients with epileptic spasms and 4 of them showed response. All patients showed different degrees of developmental delay while four of them showed autistic features. STXBP1 gene mutations were identified in all cases and there were 15 types of gene variations, including 8 missense mutations, 1 nonsense mutation, 5 frame shift mutations and 1 complex mutation. Five novel mutations were unreported before, including c.1193A>G, c.172delG, c.1769C>T, c.1038_1039delCC, c.348_351dupTGAA. Conclusions: Development delay and epilepsy are the major and independent clinical phenotypes in children with STXBP1 encephalopathy. The variation of STXBP1 gene is mainly de novo. Levetiracetam and vigabatrin may be more effective in epilepsy control than other AEDs.

[Associated factors of different fatigue dimensions in elderly patients with rheumatoid arthritis].

Objective: To investigate the associated factors of different dimensions of fatigue in elderly patients with rheumatoid arthritis (RA). Methods: A cross-sectional analysis was performed in the elderly outpatients with RA (age ≥ 60 years) in the First Affiliated Hospital of Sun Yat-sen University from January 2018 to June 2019. Fatigue was measured by Multidimensional Fatigue Inventory-20 (MFI-20) and 36-item Short Form Health Survey-Vitality (SF-36-VT). Physical fatigue and mental fatigue were subsequently measured by MFI-20 subscales. Results: A total of 104 patients were included. Male-to-female ratio was 1∶3.3. The average age was (68±6) years. The MFI-20 score and SF-36-VT score were 60±14 and 64±20, respectively. The score of physical fatigue measured by MFI-20 was 14±3, and mental fatigue scored 10±4 (P<0.001). Arthralgia, disease activity, disability, insomnia, depression and anxiety were correlated with fatigue assessed by MFI-20 (correlated coefficient: 0.48-0.62). Multivariable regression analysis showed that arthralgia and depression were associated with physical fatigue (Standardized regression coefficients were 0.44 and 0.38, respectively). Insomnia, depression and anxiety were associated factors of mental fatigue (Standardized regression coefficients were 0.20, 0.32 and 0.24, respectively). Conclusions: Elderly patients with RA experiencehigh level of fatigue, mainly presenting as physical fatigue. Arthralgia and depression mainly affect physical fatigue, and arthralgia is a critical factor. Insomnia, depression and anxiety are associated with mental fatigue.

[Albumin-to-bilirubin scores for assessing the prognosis in autoimmune hepatitis-related cirrhosis].

Objective: To investigate the prognostic value of albumin-to-bilirubin scores in the assessment of autoimmune hepatitis-related cirrhosis. Methods: The receiver operating characteristic curve was used to evaluate the accuracy of ALBI, Child-Pugh and model for end-stage liver disease (MELD) for prognosis prediction. Survival analysis was performed according to the ALBI classification. Spearman correlation analysis was performed on the ALBI score and the Child-Pugh score. Survival curves were plotted by Kaplan-Meier method, and Log-rank method was used to compare the survival difference curves between different groups. Results: 149 patients were recruited in the study. The ROC analysis showed that the ALBI scores (0.861, 0.826, 0.779, 0.744)was superior to Child-Pugh scores(0.703, P = 0.006; 0.672, P < 0.001; 0.613, P < 0.001; 0.583, P < 0.001)and MELD score(0.774, P = 0.031; 0.731, P = 0.007; 0.669, P < 0.001; 0.631, P < 0.001) for predicting 6, 12, 24, and 36 months mortality. Patients with ALBI grade 3 had a significantly lower survival rate than those with ALBI grade1 and grade 2. Conclusion: ALBI score may be useful to evaluate the long-term prognosis of patients with autoimmune hepatitis-related cirrhosis.

[A phenotypic and genetic study on ß-propeller protein-associated neurodegeneration].

Objective: To summarize the clinical and genetic features of ß-propeller protein-associated neurodegeneration (BPAN). Methods: The clinical data of 17 patients with BPAN with WDR45 gene variants were retrospectively collected at Children's Hospital of Fudan University, Peking University First Hospital, Capital Institute of Pediatrics, Shengjing Hospital of China Medical University and Shanghai Children's Hospital from June 2016 to December 2018, and their clinical manifestations, electroencephalogram, neuroimaging and genetics were analyzed. Results: Seventeen cases (13 females, 4 males), aged 1.1-8.8 years, were included. The median age of seizure onset was 14.5 months, from 3 months to 24 months of age, manifested with epileptic spasm in 6 cases and focal seizures in 5 cases. Eight patients had only one seizure type and 8 patients had two or more seizure types. Nine patients had complete remission of seizures. All 16 patients with seizures had developmental delay before the seizure onset, of whom 13 patients had moderate to severe seizures. The brain magnetic resonance imaging (MRI) was abnormal in 13 patients, including cerebral atrophy (10 cases) and thinning of the corpus callosum (9 cases). The brain magnetic susceptibility weighted imaging (SWI) in preschool stage showed prominent T2 hypointense signals in bilateral globus pallidus and brainstem ventral in two cases. Five seizure types (spasm, focal, absence, myodonic and generalized tonic clonic seizures)were found on ictal electroencephalogram(EEG) recordings. Compared to female patients(17(6-24) months of ege), male cases had earlier seizure onset (3, 4, 5, 18 months of age) . All patients had de novo variations in WDR45(6 nonsense, 4 frameshift, 3 missense and 4 splicing variations), with hemizygous variants in 3 males, mosaic variants in a male and heterozygous variants in 13 females, within which 5 variations had not been reported (c.977-1C>T,c.976+1G>C,c.10C>T,c.806del and c.110T>C). Conclusions: The patients with BPAN have profound developmental delay and are vulnerable to seizures. The male patients with BPAN tend to have more severer clinical phenotype than females. Early brain SWI could facilitate the timely diagnosis of this disease.

[Analysis and comparison of the clinical features and prognosis between extra - gastrointestinal stromal tumors and duodenal gastrointestinal stromal tumors].

Objective: To investigate the differences of clinicopathological features, diagnosis, treatment and prognosis between patients with extra-gastrointestinal stromal tumors (EGIST) and duodenal gastrointestinal stromal tumors (DGIST). Methods: A retrospective case - control study was performed. Case inclusion criteria: (1) tumor confirmed by histology and pathology; (2) primary tumor locating in the extra - gastrointestinal tract or duodenum; (3) without other synchronous tumors; (4) complete clinical and pathological data. Clinical data of 20 EGIST patients and 32 DGIST patients from March 2011 to September 2016 at Department of Gastrointestinal Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine were retrospectively collected and analyzed. The observational parameters included clinicopathological characteristics, treatment and prognosis conditions. Continuous data of abnormal distribution were expressed as median (range) and compared using the Mann-Whitney U-test. Survival curves were drawn by the Kaplan-Meier method and compared with the Log-rank test. Results: Of the 20 EGIST patients, 8 were males and 12 were females with age of 61.0 (30.0 to 86.0) years and of the 32 DGIST patients, 12 were males and 20 were females with age of 55.5 (27.0 to 70.0) years. Compared with DGIST patients, EGIST patients were older (U=188.000, P=0.012], had larger tumor size [10.0 (3.0 to 29.0) cm vs. 4.0 (1.5 to 10.0) cm, U=98.500, P<0.001] and higher ratio of high risk classification [85.0% (17/20) vs. 12.5% (4/32), χ(2)=26.870, P<0.001]. Among the 20 EGIST patients, 5 were diagnosed with distal metastasis and received imatinib (400 mg/d), and the other 15 patients underwent radical resection who were included in survival analysis. All the 32 DGIST patients underwent radical resection. The median follow-up of whole group was 43 (14 to 76) months. The 3-year recurrence/metastasis-free survival rate of 15 cases undergoing radical resection in the EGIST group was 85.6%, which was lower than that of the DGIST group (88.6%), and the difference was not statistically significant (P=0.745). There was no significant difference in the 3-year overall survival rate between the EGIST group (92.9%) and the DGIST group (100%) (P=0.271). Conclusions: As compared to DGIST, EGIST mostly occurs in those with older age, larger tumor size and higher risk grade. The prognosis of EGIST patients after radical resection is similar to that of DGIST patients.

[Predictive factors for lymph node metastasis in patients with poorly differentiated early gastric cancer].

Objective: This study aimed to identify clinicopathological factors predictive of lymph node metastasis in patients with the poorly differentiated early gastric cancer (EGC) to assess the feasibility of using endoscopic submucosal dissection (ESD). Methods: The records of patients with poorly differentiated early gastric cancer undergoing gastric radical resection between January 2012 and December 2016 were reviewed in Ruijin hospital. Those with distant metastasis, two or more malignant tumors, remnant gastric cancer, neo adjuvant therapy, previous history of gastric surgery or clear history of perigastric lymphadenectomy, and mixed tumors were excluded. Age, sex, presence of ulcerous lesion, tumor size, tumor location, depth of invasion, type of differentiation, lymphatic vessel invasion, vascular invasion, nerve invasion and HER2 expression were collected. Univariate and multivariate stepwise logistic regression analyses were used to identify the independent risk factors of perigastric lymph node metastasis.According to the Guidelines for the Treatment of Gastric Cancer (2018 edition) of the Chinese Society of Clinical Oncology (CSCO), the expanded indications of ESD for EGC are as follows: (1)no ulcerative lesions, the maximum diameter of lesions >2 cm of differentiated intramucosal cancer; (2)ulcerative lesions, the maximum diameter of lesions ≤3 cm of differentiated intramucosal cancer; (3)no ulcerative lesions, undifferentiated intramucosal carcinoma with diameter ≤2 cm. The relationship between clinicopathological factors and lymph node metastasis was analyzed. Results: A total of 517 patients, aged 21-83 (57.1±11.7), including 307 males and 210 females, were enrolled in the study. Among them, 114 (22.0%) patients had lymph node metastasis. Univariate analysis showed that ulcerative lesion (P=0.042), tumor diameter (P=0.048), depth of invasion (P<0.001), location of tumors (P<0.001), lymphatic vessel invasion (P=0.009), vascular invasion (P<0.001) and nerve invasion (P=0.028) were related to lymph node metastasis after radical resection of poorly differentiated early adenocarcinoma. Age, sex, type of differentiation and HER2 expression were not significantly correlated to lymph node metastasis (P>0.05). Multivariate analysis showed that tumor size (OR=1.61, 95% CI: 1.03-2.52, P=0.037), depth of invasion (OR=2.77, 95% CI:1.66-4.63, P<0.001), lymphatic duct invasion (OR=14.74, 95% CI:1.58-137.36, P=0.018) were independent risk factors for lymph node metastasis in poorly differentiated EGC, and ulcerative lesion was not a risk factor for lymph node metastasis (OR=0.82, 95% CI:0.56-1.18,P=0.285). A total of 119 patients with poorly differentiated EGC fully complied with the relative indications of ESD recommended by the Japanese Statute and the criteria for radical resection after ESD. Among them, 14 (11.8%) still had perigastric lymph node metastasis, while the gender, tumor diameter, location, differentiation and HER2 expression were not associated with lymph node metastasis (P>0.05). Conclusion: For patients with poorly differentiated EGC, the application of ESD should be carefully weighed with precise assessment of tumor diameter, depth of invasion, and lymphatic duct invasion.

Valsartan improves cardiac function in mice with diabetes mellitus by CaMKII/AngII.

OBJECTIVE: To investigate whether valsartan exerts its effect on cardiac function in mice with diabetes mellitus (DM) via Ca2+/calmodulin-dependent protein kinase II (CaMKII). MATERIALS AND METHODS: C57bl6/J mice were used as study subjects and randomly divided into three groups: 1) control group, 2) DM group and 3) valsartan group. After the model was successfully established, the diastolic function in each group of mice was detected via echocardiography, including the ratio of peak velocity blood flow in early diastole to peak velocity blood flow in late diastole (E/A ratio) of mitral valves, isovolumic relaxation time (IVRT) and mitral deceleration time. Ejection fraction (EF), fractional shortening (ES), heart rate (HR) and cardiac output (CO) were determined to evaluate the systolic function of the mouse heart. The frozen heart was stained by dihydroethidium (DHE) and analyzed for the oxidative stress and inflammation levels. The expression levels of phosphorylated calmodulin-dependent protein kinase II (P-CaMKII), oxidized CaMKII (O-CaMKII), ryanodine receptor 2 (RYR2), P-phospholamban (P-PLN) and PLN in tissues were detected via Western blotting. RESULTS: Valsartan improves myocardial diastolic and systolic function in DM mice by improving phosphorylation and oxidation levels of CaMKII in myocardial cells, and reducing oxidative stress in diabetic cardiomyopathy. CONCLUSIONS: Valsartan could improve CaMKII in myocardial cells to enhance oxidative stress of DM mice, thus improving the cardiac function.

[Evaluation of maxillary three-dimensional changes in maxillary protraction with alternating rapid palatal expansion and constriction based on the cone-beam computed tomography].

OBJECTIVE: To use the cone-beam computed tomography (CBCT) to evaluate the three-dimensional (3D) changes of maxillary landmarks in the maxillary protraction with alternating rapid palatal expansion and constriction and with rapid palatal expansion, and to provide some clinical suggestions for the early treatment of Class III malocclusion. METHODS: A total of 36 maxillary retrusive patients were included and randomized in a 1:1 ratio to either the intervention group (alternating rapid palatal expansion and constriction group, RPE/C) or the control group (rapid palatal expansion group, RPE). Randomization was accomplished with permuted block randomization based on participation sequence. The patients in the RPE/C were treated for 10 weeks (0.5 mm/d) with the repetition of two-week palatal expansion and two-week palatal constriction. The patients in the RPE were taught to complete rapid palatal expansion for 2 weeks (0.5 mm/d ). The patients were instructed to come to the office for the follow-up to ensure the correct procedures. Damaged expanders were repaired (or replaced) and rebanded quickly. Sequential CBCT images including pretreatment (T1), post-expansion (T2) and post-protraction (T3) were required for 3D reconstruction, establishment of landmarks, measurement and analysis by Mimics 10.01. RESULTS: There was significant forward movement of subspinale (A) in the RPE/C after the treatment with (3.06±1.29) mm, compared with RPE (2.16±1.27) mm, P<0.05. There were more symmetrical changes of the landmarks in the RPE/C and there was no statistic significance of the entire treatment time between the two groups. Moreover, the maxillary skeletal landmarks had the following 3D changes of a forward and downward movement during the expansion stages T2-T1, a forward and upward movement during the protraction stages T3-T2 and a forward and downward movement during the total treatments T3-T1 compared with the control group. And the width between the bilateral landmarks increased during the expansion stages T2-T1, narrowed down during the protraction stages T3-T2 and increased during the total treatments T3-T1. CONCLUSION: The maxillary protraction with alternating rapid palatal expansion and constriction provided clinical benefits on maxillary advancement and symmetrical changes in the orthopedic treatment of the patients with maxillary retrognathism and it required further study on the orthodontic analysis and measurements of CBCT.

Aberrant expression of Rab1A and its prognostic significance in human colorectal cancer.

OBJECTIVE: Colorectal cancer (CRC) is one of the most common types of cancer worldwide. Emerging evidence has verified that Rab1A plays an oncogenic role in several human malignancies including breast cancer, lung cancer, and hepatocellular carcinomas. However, the clinical significance and prognostic impact of Rab1A in CRC is still unclear. PATIENTS AND METHODS: We initiated our investigation by immunohistochemistry and Western blot analysis to confirm Rab1A expression in CRC tissues. Meanwhile, the correlation of Rab1A expression and clinicopathologic features, as well as outcome in CRC patients, were retrospectively analyzed. RESULTS: In the issue, Rab1A is overexpressed in CRC tissues compared with matched noncancerous tissues. Meanwhile, high Rab1A expression was significantly associated with the TNM stage, lymph node metastasis, and peritoneal metastasis. In addition, multivariate analyses identified Rab1A expression and TNM stage as independent predictors for CRC patients. Moreover, Kaplan-Meier survival analysis showed that patients with high Rab1A expression had a significantly worse survival time than those with low Rab1A expression, which especially affected the survival in CRC patients with advanced stage. Spearman analysis suggested that there was a positive relationship between Rab1A expression and preoperative serum carcinoembryonic antigen (CEA) for CRC patients. CONCLUSIONS: These results suggested that Rab1A is an important diagnostic marker for CRC, and Rab1A can be used as a valuable biomarker for prognosis as well as peritoneal metastasis in CRC patients. Rab1A may prove to be clinically useful for developing a new therapeutic target of CRC treatment.

Microbial community composition and diversity in rice straw digestion bioreactors with and without dairy manure.

Anaerobic digestion (AD) uses a range of substrates to generate biogas, including energy crops such as globally abundant rice straw (RS). Unfortunately, RS is high in lignocellulosic material and has high to C:N ratios (~80:1), which makes it (alone) a comparatively poor substrate for AD. Co-digestion with dairy manure (DM) has been promoted as a method for balancing C:N ratios to improve RS AD whilst also treating another farm waste and co-producing a potentially useful fertiliser. However, past co-digestion studies have not directly compared RS AD microbial communities with and without DM additions, which has made it hard to assess all impacts of DM addition to RS AD processes. Here, four RS:DM ratios were contrasted in identical semi-continuous-fed AD bioreactors, and 100% RS was found to produce the highest specific methane yields (112 mL CH4/g VS/day; VS, volatile solids), which is over double yields achieved in the reactor with the highest DM content (30:70 RS:DM by mass; 48 mL CH4/g VS/day). To underpin these data, microbial communities were sequenced and characterised across the four reactors. Dominant operational taxonomic units (OTUs) in the 100% RS unit were Bacteroidetes/Firmicutes, whereas the 30:70 RS:DM unit was dominated by Proteobacteria/Spirochaetes, suggesting major microbial community shifts occur with DM additions. However, community richness was lowest with 100% RS (despite higher specific yields), suggesting particular OTUs may be more important to yields than microbial diversity. Further, ambient VFA and VS levels were significantly higher when no DM was added, suggesting DM-amended reactors may cope better with higher organic loading rates (OLR). Results show that RS AD without DM addition is feasible, although co-digestion with DM will probably allow higher OLRs, resulting in great RS throughput in farm AD units.

Paeoniflorin attenuates postoperative pain by suppressing Matrix Metalloproteinase-9/2 in mice.

BACKGROUND: Recent studies have implicated that matrix metalloproteinase (MMP)-9 and MMP-2 play key roles in neuropathic pain due to their facilitation of inflammatory cytokine maturation and induction of neuroinflammation. However, the role of MMP-9/2 in postoperative pain is still unclear. We previously suggested that the natural compound paeoniflorin inhibited microglia activation induced by morphine treatment. In the present study, we demonstrated that paeoniflorin could alleviate postoperative pain via specific inhibition of matrix metalloproteinases (MMPs). METHODS: Mice received a plantar incision surgery and their mechanical allodynia was assessed with von Frey filaments. The activity of MMP-9/2 was determined by gelatin zymography. Cell signalling was assayed by western blot and immunohistochemistry. RESULTS: The expression of MMP-9/2 was significantly increased in mice spinal cords with plantar incision surgery. Paeoniflorin remarkably suppressed the activity of MMP-9/2 and relieved plantar incision-induced mechanical allodynia. Interestingly, the administration of paeoniflorin blocked the maturation of interleukin-1ß, which is a critical substrate of MMPs. Thereafter, paeoniflorin markedly suppressed microglia activation, inhibited the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and the expression of neuronal c-Fos. CONCLUSION: These results indicated that MMP-9/2 activation in spinal microglia plays a key role in incision-induced mechanical allodynia in mice. Moreover, utilizing paeniflorin blockage of the microglia MMP-9/2 activity might represent a valuable alternative for treating postoperative pain. SIGNIFICANCE: Our results provided direct evidence for the first time that paeoniflorin can inhibit plantar incision-induced microglia TLR4/MMP-9/2/IL-1ß signalling pathway and suppress postoperative pain. Thus, regulation of microglia MMP-9/2 may provide a new strategy for ameliorating postoperative pain.

[Clinical features of autoimmune hepatitis patients with poor response to treatment].

Objective: To investigate the clinical features of autoimmune hepatitis (AIH) patients with poor response to treatment. Methods: A total of 61 AIH patients were enrolled, among whom 49 (80.33%) achieved complete response (good response group) and 12 (19.67%) had incomplete response (poor response group). The two groups were compared in terms of clinical manifestations, laboratory markers, abdominal ultrasound findings, pathological features by liver biopsy, and response to treatment. Continuous data were expressed as mean ± standard deviation (x±s), and the t-test was used for comparison between groups; categorical data were expressed as rates or percentages, and the chi-square test was used for comparison between groups; a binary logistic regression analysis was used to determine influencing factors. Results: Most patients were female in both groups, and there were no significant differences in sex ratio, mean age of onset, and general status including extrahepatic autoimmune disease between the two groups. Compared with the good response group, the poor response group had significantly higher levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (ALP), total bilirubin, immunoglobulin G, and immunoglobulin M (P < 0.05). Compared with the good response group, the poor response group had a significantly higher positive rate of autoimmune antibodies except anti-nuclear antibody (ANA), anti-smooth muscle antibody (SMA), antimitochondrial antibody (AMA), and AMA/M2 (75% vs 16.3%, P < 0.001), and there was a significant difference in the positive rate of gp210 antibody between the two groups (25% vs 0%, P < 0.01). There were significant differences between the poor response group and the good response group in the proportion of patients with liver cirrhosis (50.0 % vs 16.3%, P < 0.05) and splenomegaly (58.3% vs 22.4%, P < 0.05). The binary logistic regression analysis showed that a high serum level of ALP (odds ratio [OR] = 1.017, 95% confidence interval [CI] 1.001-1.033, P = 0.034), positive autoimmune antibodies except ANA, SMA, and AMA/M2 (OR = 70.842, 95% CI 2.132-2 354.371, P = 0.017), and liver cirrhosis (OR = 28.777, 95% CI 1.015-815.854, P = 0.049) were independent risk factors for initial treatment outcome. Conclusion: A high serum level of ALP, positive autoimmune antibodies except ANA, SMA, and AMA/M2, and liver cirrhosis are closely associated with poor response in AIH patients.

[Evaluation of cone-beam computed tomography on upper airway changes after alternating rapid palatal expansion and constriction].

OBJECTIVE: To evaluate the changes of different parts of upper airway after alternating rapid palatal expansion and constriction via three dimensional measurement, compared with the protocol of rapid palatal expansion alone. METHODS: In the study, 36 patients with retrognathic maxilla were selected and randomized to either group A or group B. The patients in group A were treated with rapid palatal expansion alone. The patients in group B were treated with alternating rapid palatal expansion and constriction. Three dimensional analyses were performed on all pre- and post-treatment cone-beam computed tomography (CBCT) images with the software Dolphin. RESULTS: Two subjects in group B were lost to follow up during the treatment. The gender distributions, ages and all measuring items before treatment had no significant difference between group A and group B (P>0.05). Nasal floor width, nasal lateral width, nasal volume, and nasopharynx volume increased significantly in each group after rapid palatal expansion alone or rapid palatal expansion and constriction (P<0.05). The variations of oropharyngeal volume and hypopharyngeal volume had no significant difference (P>0.05). No significant difference was observed in the nasal floor width and nasal lateral width increment among the anterior, median and posterior parts in each group either (P>0.05). No significant difference in all the measuring items was observed between the two groups (P>0.05). CONCLUSION: Alternating rapid palatal expansion and constriction could increase the volume of nasal and naopharynx cavities by the similar way of rapid palatal expansion alone, and had no obvious effect on oropharynx and hypopharynx cavities.

TGF-ß upregulates the translation of USP15 via the PI3K/AKT pathway to promote p53 stability.

Crosstalk between transforming growth factor beta (TGF-ß) signaling and p53 has a critical role in cancer progression. TGF-ß signals via Smad and non-Smad pathways. Under normal conditions, wild-type p53 forms a complex with Smad2/3 and co-activates transcription of a variety of tumor suppressor genes, resulting in tumor suppressive effects. Thus, p53 stability is essential in progression of tumor suppressive responses mediated by TGF-ß signaling. However, it remains unknown whether p53 stability is regulated by TGF-ß. In the current study, we identify that USP15 binds to and stabilizes p53 through deubiquitination in U2OS and HEK293 cells. TGF-ß promotes the translation of USP15 through activation of mammalian target of rapamycin by the phosphoinositide 3-kinase/AKT pathway. Upregulation of USP15 translation links the crosstalk between TGF-ß signaling and p53 stability, allowing this cytokine to have a critical role in cancer progression.

Effects of heat shocks on microbial community structure and microbial activity of a methanogenic enrichment degrading benzoate.

In anaerobic digesters, temperature fluctuation could lead to process instability and failure. It is still not well understood how digester microbiota as a whole respond to heat shock, and what specific organisms are vulnerable to perturbation or responsible for process recovery after perturbation. To address these questions, a mesophilic benzoate-degrading methanogenic culture enriched from digester was subjected to different levels of heat shock. Three types of methane production profiles after perturbation were observed in comparison to the control: uninhibited, inhibited with later recovery, and inhibited without recovery. These responses were correlated with the microbial community compositions based on the analyses of 16S rRNA and 16S rRNA gene. Specifically, the primary benzoate-degrading syntroph was highly affected by heat shock, and its abundance and activity were both crucial to the restoration of benzoate degradation after heat shock. In contrast, methanogens were stable regardless whether methane production was inhibited. Populations related to 'Candidatus Cloacimonetes' and Firmicutes showed stimulated growth. These observations indicated distinct physiological traits and ecological niches associated with individual microbial groups. The results obtained after exposure to heat shock can be critical to more comprehensive characterization of digester ecology under perturbations. SIGNIFICANCE AND IMPACT OF THE STUDY: Anaerobic digestion is an essential step in municipal wastewater treatment owing to its striking capacity of reducing wasted sludge and recovering energy. However, as an elaborate microbial process, it requires constant temperature control and is sensitive to heat shock. In this study, we explored the microbial response to heat shock of a methanogenic culture enriched from anaerobic digester sludge. Microorganisms that were vulnerable to perturbation or responsible for process recovery after perturbation were identified.