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.

[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.

[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.

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.

[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.

[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.

[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.

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.

Anti-osteoporosis activity of red yeast rice extract on ovariectomy-induced bone loss in rats.

Osteoporosis is the most common bone disease, affecting millions of people worldwide and leading to significant morbidity and high costs. Monacolin K, an extract of red yeast rice (RYR, Hongqu), plays important roles in the management of dyslipidemia, coronary heart disease, and diabetes. Our study aimed to investigate the protective effect of monacolin K on ovariectomy-induced bone loss in rats. Fifty female Sprague-Dawley rats were randomly divided into a sham-operated and five ovariectomized (OVX) groups: OVX with vehicle, OVX with fluvastatin, and OVX with RYR extract of three graded doses. Bone mineral density (BMD), biochemical markers, and cell viability were analyzed by dual energy X-ray absorptiometry, enzyme-linked immunosorbent assay, and 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. Gene expression was evaluated by real-time polymerase chain reaction amplification and western blot. Our results showed that administration of RYR extract markedly increased the bone mineral density in OVX rats. Moreover, RYR extract decreased the levels of bone turnover markers, including osteocalcin and tartrate resistant acid phosphatase activity. The MMT assay revealed that RYR extract treatment significantly improved the osteoblast viabilities in a dose-dependent manner (P < 0.05). At the molecular level, we further demonstrated that RYR extract enhanced the expression of Bmp2 and Bmp4 both at the mRNA and protein levels. Collectively, these data suggested RYR extract could protect against osteoporosis in ovariectomized rats, most likely through activation of BMP2/4 expression.

Seasonal concentrations, contamination levels, and health risk assessment of arsenic and heavy metals in the suspended particulate matter from an urban household environment in a metropolitan city, Beijing, China.

The levels and health risks of arsenic and heavy metals (As, Ba, Cd, Co, Cr, Cu, Mn, Ni, Pb, and Zn) in the suspended particulate matter (SPM) collected from an urban household environment in Beijing of China for 12 months were investigated. The mean concentrations of the studied toxic elements were higher and lower than crustal abundance and PM2.5 in the urban outdoors of Beijing. The concentrations of the studied elements displayed significant seasonality. The highest concentrations of the total elements occurred in winter, followed by autumn, while the lowest concentrations were recorded in summer. Based on the calculated values of enrichment factor (EF) and geoaccumulation index (Igeo), the levels for As and Cu were heavily contaminated, while those for Cd, Pb, and Zn were extremely contaminated. As and Pb might pose risks to children and adults via ingestion exposure. The accumulative risks of multi-elements resulted from dermal contact and inhalation exposures were not negligible. More attention should be paid to reducing the non-carcinogenic and carcinogenic health risks posed by the toxic elements bound to urban household SPM particles via ingestion, inhalation, and dermal contact exposure.

Pyrosequencing reveals bacterial communities in unchlorinated drinking water distribution system: an integral study of bulk water, suspended solids, loose deposits, and pipe wall biofilm.

The current understanding of drinking water distribution system (DWDS) microbiology is limited to pipe wall biofilm and bulk water; the contributions of particle-associated bacteria (from suspended solids and loose deposits) have long been neglected. Analyzing the composition and correlation of bacterial communities from different phases helped us to locate where most of the bacteria are and understand the interactions among these phases. In the present study, the bacteria from four critical phases of an unchlorinated DWDS, including bulk water, pipe wall biofilm, suspended solids, and loose deposits, were quantified and identified by adenosine triphosphate analysis and pyrosequencing, respectively. The results showed that the bulk water bacteria (including the contribution of suspended solids) contributed less than 2% of the total bacteria. The bacteria associated with loose deposits and pipe wall biofilm that accumulated in the DWDS accounted for over 98% of the total bacteria, and the contributions of bacteria in loose deposits and pipe wall biofilm were comparable. Depending on the amount of loose deposits, its contribution can be 7-fold higher than the pipe wall biofilm. Pyrosequencing revealed relatively stable bacterial communities in bulk water, pipe wall biofilm, and suspended solids throughout the distribution system; however, the communities present in loose deposits were dependent on the amount of loose deposits locally. Bacteria within the phases of suspended solids, loose deposits, and pipe wall biofilm were similar in phylogenetic composition. The bulk water bacteria (dominated by Polaromonas spp.) were clearly different from the bacteria from the other three phases (dominated by Sphingomonas spp.). This study highlighted that the integral DWDS ecology should include contributions from all of the four phases, especially the bacteria harbored by loose deposits. The accumulation of loose deposits and the aging process create variable microenvironments inside loose deposits structures for bacteria to grow. Moreover, loose deposits protect the associated bacteria from disinfectants, and due to their mobility, the associated bacteria reach taps easily.

Whole exome sequencing implicates PTCH1 and COL17A1 genes in ossification of the posterior longitudinal ligament of the cervical spine in Chinese patients.

Ossification of the posterior longitudinal ligament (OPLL) of the cervical spine is a complex multifactorial disease. Patients with OPLL commonly present with symptoms in their 40s or 50s. The genetic basis of OPLL remains poorly understood. Exome capture combined with massively parallel DNA sequencing has been proposed as an efficient strategy to search for disease-causing genes of both monogenic and multigenic disorders. To identify candidate pathogenic genes associated with OPLL, we performed whole exome sequencing (WES) on two unrelated southern Chinese OPLL patients. The entire DNA coding region of the candidate genes was amplified by PCR and Sanger sequenced. The common single nucleotide polymorphisms were analyzed by association studies. WES revealed p.T265S/PTCH1, p.P1232L/PTCH1, and p.T902S/COL17A1 mutants in the two female cases with mixed OPLL. These were confirmed by Sanger sequencing. p.P1232L/PTCH1, p.N1374D/COL17A1 and p.T902S/COL17A1 were subsequently identified in three males with continuous OPLL and one female with mixed OPLL. The association studies indicated that the SNPs rs805698 and rs4918079 in COL17A1 were significantly associated with OPLL. This study suggests that WES may be a practical approach to revealing significant genetic involvement in OPLL. Variants of the PTCH1 and COL17A1 genes may contribute to the development of OPLL.

A mobile telephone-based interactive self-care system improves asthma control.

The self-management of asthma can improve clinical outcomes. Recently, mobile telephones have been widely used as an efficient, instant personal communication tool. This study investigated whether a self-care system will achieve better asthma control through a mobile telephone-based interactive programme. This was a prospective, controlled study in outpatient clinics. From 120 consecutive patients with moderate-to-severe persistent asthma, 89 were eventually recruited for the study, with 43 in the mobile telephone group (with a mobile telephone-based interactive asthma self-care system). In the mobile telephone group, mean ± sem peak expiratory flow rate significantly increased at 4 (378.2 ± 9.3 L·min⁻¹; n = 43; p = 0.020), 5 (378.2 ± 9.2 L·min⁻¹; n = 43; p = 0.008) and 6 months (382.7 ± 8.6 L·min⁻¹; n = 43; p = 0.001) compared to the control group. Mean±sem forced expiratory volume in 1 s significantly increased at 6 months (65.2 ± 3.2% predicted; n = 43; p < 0.05). Patients in the mobile telephone group had better quality of life after 3 months, as determined using the Short Form-12® physical component score, and fewer episodes of exacerbation and unscheduled visits than the control group. Patients in the mobile telephone group significantly increased their mean daily dose of either systemic or inhaled corticosteroids compared with the control group. The mobile telephone-based interactive self-care system provides a convenient and practical self-monitoring and -management of asthma, and improves asthma control.

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.

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.

Microbial population dynamics of granular aerobic sequencing batch reactors during start-up and steady state periods.

This study investigates microbial population dynamics in granular sequencing batch reactors (GSBR). The experimental results of DGGE fingerprint of sludge demonstrated that the microbial community structure of sludge shifted significantly during granulation period and nutrient removal improvement period. After reactor performance and physical characteristics of sludge reached steady state, microbial population of sludge became relatively stable. The high similarity of microbial community structure between co-existed flocculated sludge and granular sludge in GSBR at different operation phases indicated that similar microbial consortium could exist in compact aggregated form or in amorphous flocculated form. Therefore, strong selection pressure was still required to wash out flocs to maintain the stability of reactor operation. In addition, it was found that substrate type had considerable impact on microbial species selection and enrichment in granular sludge. The clone library of granular sludge showed that microbial species in divisions of α-Proteobacteria, ß-Proteobacteria, γ-Proteobacteria and Bacteroidetes existed within acetate-fed granule communities and Thauera spp. from ß-Proteobacteria accounted for 49% of the total clones in the whole clone library. It is thus speculated that Thauera spp. are important for the formation of acetate-fed granules under the conditions used in this study, maintaining the integrity of granules or substrate degradation.

[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.

[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.