Dynamic changes of viral load and the duration of viral shedding in patients with hand, foot and mouth disease: a protocol for longitudinal study.

BACKGROUND: The duration of virus shedding is necessary for determining the infectious period. But there were few quantitative studies on the changes of viral load and the law of the viral shedding in hand foot and mouth disease (HFMD) patients has not yet been clarified. METHODS: This study will prospectively recruit coxsackievirus A10 (CV-A10), coxsackievirus A16 (CV-A16) and coxsackievirus A6 (CV-A6) infected inpatients from January 2022 to December 2022. A series of samples and questionnaire information will be collected regularly to establish the dynamic function relationship between time and viral load changes and a Bayesian multilevel model will be constructed to clarify the evolvement rules which reflect the dynamic changes of viral load and the duration of viral shedding in patients with HFMD. DISCUSSION: The results of this study is expected to further clarify the evolvement rules which reflect the dynamic changes of viral load and the duration of viral shedding in HFMD patients under the influence of related factors. It can also provide important evidence for the scientific definition of the infectious period and isolation period of HFMD in China.

[Epidemiological Characteristics of Hand, Foot, and Mouth Disease and the Effect of EV71 Vaccination in Chengdu from 2012 to 2020].

Objective: To analyze the epidemiological characteristics of hand, foot, and mouth disease (HFMD) in Chengdu from 2012 to 2020, to make comparison in order to examine the changes in incidence before and after vaccination was introduced, and to provide basis for the prevention of HFMD in the future. Methods: Descriptive epidemiological methods were adopted to analyze the incidence, mortality and rate of severe cases of HFMD cases reported in Chengdu from 2012 to 2020. Results: From 2012 to 2020, the cumulative cases of HFMD reported in Chengdu were as many as 279216, of which, there were 2201 severe cases and 16 deaths. The incidence increased every other year, reaching 326.43 per 100000 person-years, the highest ever, in 2018. The rate of severe cases and mortality had shown a decreasing trend since 2016. A total of 11892 cases of EV71, CoxA16 and other enteroviruses were detected in the laboratory, accounting for 14.8%, 18.8% and 66.3%, respectively. Since 2016, HFMD cases caused by EV71 virus infection had shown an overall decreasing trend, cases caused by Cox A16 virus infection had increased every other year, and cases caused by other enteroviral infections had shown an overall increasing trend. The reported cases were mainly concentrated in children aged 0-5 years (92.1%), with those in the age group of 1-2 years reporting the highest number of cases. For children of different ages, male patients always outnumber female patients. The geographic distribution showed that the areas with high HFMD incidence were always located in the central part of Chengdu City, and the three districts with the highest incidence growth rate were Qingbaijiang District, Shuangliu District, and Longquanyi District. Temporal distribution of HFMD cases showed an obvious bimodal distribution, with most of the cases concentrated in May through August and October through December of each year. The number of new cases reached the highest (12309 cases) in July 2018. Conclusion: While continuing to promote EV71 vaccination in the future, Chengdu also needs to pay more attention to viral infection serotypes other than EV71 and Cox A16 and conduct research on multivalent vaccines against a variety of enteroviruses. The focus of prevention and control can be placed on areas with high population density, large floating populations, large numbers of agriculture-related communities, and insufficient individual awareness of hygiene. For the second circle of Chengdu city, the disinfection of agriculture-related communities should be strengthened, and information sessions or other health education activities could be organized for individuals and daycare facilities with low awareness of the importance of hygiene. In addition, more attention should be given to the prevention and control of HFMD in the high incidence seasons.

Injectable hydrogel encapsulating Cu2MnS2 nanoplates for photothermal therapy against breast cancer.

BACKGROUND: In order to explore the possibility of treating breast cancer by local photo-therapy, a photothermal agents loaded in situ hydrogel was established. In detail, The Cu2MnS2 nanoplates were prepared by one-pot synthesis and, the thermosensitive Pluronic F127 was used as the hydrogel matrix. The Cu2MnS2 nanoplates and the hydrogel were characterized by morphous, particle size, serum stability, photothermal performance upon repeated 808 nm laser irradiation as well as the rheology features. The therapeutic effects of the Cu2MnS2 nanoplates and the hydrogel were evaluated qualitatively and quantitatively in 4T1 mouse breast cancer cells. The retention, photothermal efficacy, therapeutic effects and systemic toxicity of the hydrogel were assessed in tumor bearing mouse model. RESULTS: The Cu2MnS2 nanoplates with a diameter of about 35 nm exhibited satisfying serum stability, photo-heat conversion ability and repeated laser exposure stability. The hydrogel encapsulation did not negatively influence the above features of the photothermal agent. The nanoplates loaded in situ hydrogel shows a phase transition at body temperature and, as a result, a long retention in vivo. CONCLUSIONS: The photothermal agent embedded hydrogel played a promising photothermal therapeutic effects in tumor bearing mouse model with low systemic toxicity after peritumoral administration.

Evaluation of the BH3-only protein Puma as a direct Bak activator.

Interactions among Bcl-2 family proteins play critical roles in cellular life and death decisions. Previous studies have established the BH3-only proteins Bim, tBid, and Noxa as "direct activators" that are able to directly initiate the oligomerization and activation of Bak and/or Bax. Earlier studies of Puma have yielded equivocal results, with some concluding that it also acts as a direct activator and other studies suggesting that it acts solely as a sensitizer BH3-only protein. In the present study we examined the interaction of Puma BH3 domain or full-length protein with Bak by surface plasmon resonance, assessed Bak oligomerization status by cross-linking followed by immunoblotting, evaluated the ability of the Puma BH3 domain to induce Bak-mediated permeabilization of liposomes and mitochondria, and determined the effect of wild type and mutant Puma on cell viability in a variety of cellular contexts. Results of this analysis demonstrate high affinity (KD = 26 ± 5 nM) binding of the Puma BH3 domain to purified Bak ex vivo, leading to Bak homo-oligomerization and membrane permeabilization. Mutations in Puma that inhibit (L141E/M144E/L148E) or enhance (M144I/A145G) Puma BH3 binding to Bak also produce corresponding alterations in Bak oligomerization, Bak-mediated membrane permeabilization and, in a cellular context, Bak-mediated killing. Collectively, these results provide strong evidence that Puma, like Bim, Noxa, and tBid, is able to act as a direct Bak activator.

Effectiveness of enterovirus A71 vaccine against pediatric HFMD and disease profile of post-vaccination infection.

BACKGROUND: Vaccination has been proven effective against infection with enterovirus A71 (EV-A71) in clinical trials, but vaccine effectiveness in real-world situations remains incompletely understood. Furthermore, it is not clear whether previous vaccination will result in symptom attenuation among post-vaccinated cases. METHODS: Based on long-term data extracted from the only designed referral hospital for infectious diseases, we used a test-negative case-control design and multivariate logistic regression models to analyze the effectiveness of EV-A71 vaccine against hand, foot and mouth disease (HFMD). And then, generalized linear regression models were used to evaluate the associations between prior vaccination and disease profiles. RESULTS: We selected 4883 inpatients for vaccine efficacy estimations and 2188 inpatients for disease profile comparisons. Vaccine effectiveness against EV-A71-induced HFMD for complete vaccination was 63.4 % and 51.7 % for partial vaccination. The vaccine effectiveness was higher among cases received the first dose within 12 months. No protection was observed against coxsackievirus (CV) A6-, CV-A10- or CV-A16-associated HFMD among children regardless of vaccination status. Completely vaccinated cases had shorter hospital stay and disease course compared to unvaccinated cases (P < 0.05). CONCLUSIONS: These findings reiterate the need to continue the development of a multivalent vaccine or combined vaccines, and have implications for introducing optimized vaccination strategies.

Periodontitis is an immune-related adverse event associated with immune checkpoint inhibitors: A multi-center cohort study.

Immune checkpoint inhibitors (ICIs) cause immune-related adverse events (irAEs) across various organ systems including oral health complications such as dry mouth and stomatitis. In this study, we aimed to determine the risk of periodontitis among patients on immune checkpoint inhibitors (ICIs) and to test the associations between ICI-associated periodontitis and other immune-related adverse events (irAEs). We performed a retrospective cohort study involving adult cancer patients between January 2010 and November 2021. Patients on an ICI were propensity score-matched to patients not on an ICI. The primary outcome was the occurrence of periodontitis. ICIs included programmed cell death 1 (PD-1) inhibitors programmed cell death ligand 1 (PD-L1) inhibitors, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors. The risk of periodontitis following ICI use was derived through a Cox proportional hazard model and Kaplan-Meier survival analysis. Overall, 868 patients on an ICI were matched to patients not on an ICI. Among the ICI cohort, 41 (4.7 %) patients developed periodontitis. The incidence rate of periodontitis was significantly higher in patients on an ICI than in patients not on an ICI (55.3 vs 25.8 per 100 patient-years, incidence rate ratio = 2.14, 95 % CI = 1.38-3.33). Both the use of PD-L1 inhibitors (multivariate HR = 2.5, 95%CI = 1.3-4.7) and PD-1 inhibitors (multivariate HR = 2.0, 95%CI = 1.2-3.2) were associated with the risk of periodontitis. The presence of immune-related periodontitis was associated with better overall survival (not reached vs 17 months, log-rank p-value<0.001), progression-free survival (14.9 vs 5.6 months, log-rank p-value = 0.01), and other concomitant immune-related cutaneous adverse events. In conclusion, ICI was associated with an increased risk of periodontitis. Immune-related periodontitis as an irAE was associated with better cancer survival and concomitant cutaneous irAEs.

Impact of oral care modalities on the incidence of ventilator-associated pneumonia in the intensive care unit: A meta-analysis.

BACKGROUND: At present, evidence of the role of oral hygiene in ICU-related pneumonia is rare. The study aimed to evaluate the effectiveness of toothbrush-based oral care in preventing ventilator-associated pneumonia (VAP) in patients with mechanical ventilation in the ICU. METHODS: Ten databases were searched for randomized controlled trials (RCTs) evaluating toothbrush-based oral care for preventing VAP in patients with mechanical ventilation in ICU. Quality assessment and data extraction were independently performed by 2 researchers. The meta-analysis was performed using RevMan 5.3 software. RESULTS: Thirteen RCTs with 657 patients were included. Tooth brushing + 0.2%/0.12% chlorhexidine was associated with reduced incidence of VAP compared to chlorhexidine (OR = 0.63, 95% confidence interval [CI]: 0.43-0.91, P = .01) or tooth brushing + placebo (OR = 0.47, 95% CI: 0.25-0.86, P = .02) in patients with mechanical ventilation in ICU, but was similar to cotton wipe with 0.2% or 0.12% chlorhexidine (OR = 1.33, 95% CI: 0.77-2.29, P = .31). CONCLUSIONS: Tooth brushing combined with chlorhexidine mouthwash can prevent VAP in patients with mechanical ventilation in ICU. There is no advantage of tooth brushing combined with chlorhexidine mouthwash over cotton wipe with chlorhexidine mouthwash for preventing VAP in these patients.

[The influence of different preparation methods on interappointment emergency and filling effect of root canal therapy].

PURPOSE: To compare the effect of different root canal preparation methods on the incidence of interappointment emergencies (IAE) and root canal filling. METHODS: A total of 96 teeth requiring root canal therapy due to pulpitis or periapical periodontitis from August 2018 to August 2021 were selected. They were randomly divided into 2 groups: MT group was treated with Mtwo root canal preparation method modified by Mtwo machine nickel-titanium file, while synchronous group was treated with modified Mtwo preparation method and synchronous root canal length measurement. After root canal preparation, the trial point film was taken, calcium hydroxide was used to seal the root canal, and routine thermoplasticizied gutta-percha root canal filling was performed during the follow-up visit. SPSS 22.0 software package was used to analyze the incidence of IAE and filling effect after root canal therapy. RESULTS: There was no significant difference in the incidence of IAE between the two groups immediately after operation, three days and 1 week after operation(P＞0.05); the incidence of IAE in synchronous group was significantly lower than that in MT group at 1 and 2 days after operation(P＜0.05). The qualified rate of root canal filling in synchronous group was significantly higher than that in MT group (P＜0.05). CONCLUSIONS: Synchronous method can reduce mechanical stimulation of apical area during root canal preparation, strictly control the working length of root canal and maintain apical barrier, thus reducing the incidence of IAE and effectively improving the qualification rate of root canal filling.

Soft machining-induced surface and edge chipping damage in pre-crystalized lithium silicate glass ceramics.

Soft machining is a key procedure in fabrication of high-strength lithium-based silicate glass ceramic (LS) restorations. This paper reports on the diamond machining-induced surface and edge chipping damage in two pre-crystalized LS materials: pre-crystallized lithium metasilicate/orthophosphate glass ceramic (Pre-LS, IPS e.max CAD) and pre-crystallized zirconia-containing lithium metasilicate glass ceramic (Pre-ZLS, Vita Suprinity). Indentation techniques were used to measure the material mechanical properties. Soft machining was conducted using a robotic controlled apparatus mimicking dental CAD/CAM machining processes at different removal rates and enabling in-process force measurement. Machined surface roughness was assessed using 3D confocal optical profilometry in terms of the average and maximum surface heights. Scanning electron microscopy was used to assess diamond tool and machined surface and edge morphology. Soft machining of both materials was dominated by brittle fracture mixed with localized ductile flow. However, the higher brittleness index of Pre-ZLS than Pre-LS yielded higher degrees of machining-induced conchoidal fractures in Pre-ZLS in comparison with irregular fractures in Pre-LS. Thus, much larger surface roughness and deeper edge chipping damage were produced in Pre-ZLS than Pre-LS. Machining forces for Pre-ZLS were significantly smaller than Pre-LS, due to the lower machinability index associated with a complex relation of the mechanical properties as well as less debris adhesion for Pre-ZLS than Pre-LS. Further, increased material removal rates resulted in significantly increased machining forces, maximum surface roughness and fracture, and edge chipping damage in both Pre-ZLS and Pre-LS materials. Therefore, optimization of soft machining processes needs to be practiced to achieve accepted surface and edge quality at balanced removal rates.

Molecular epidemiology and clinical features of hand, foot and mouth disease requiring hospitalization after the use of enterovirus A71 inactivated vaccine in chengdu, China, 2017-2022: a descriptive study.

Three inactivated enterovirus A71 (EV-A71) vaccines have been widely vaccinated among children in the targeted age group in mainland China since mid-2016. However, comprehensive virological surveillance of hand, foot and mouth disease (HFMD) over multiple years after the use of EV-A71 vaccines has rarely been conducted. Using long-term data extracted from the Public Health and Clinical Center of Chengdu, we described the clinical, aetiological, and epidemiological characteristics of HFMD inpatients after the use of EV-A71 vaccines from 2017 through 2022. A total of 5115 patients were selected for analysis with a male-to-female ratio of 1.63:1 and were mostly under 5 years of age (97.6%). Among these cases, 4.3% presented with severe symptoms, and 4.1% of severe cases experienced significant complications. EV-A71 was no longer the major serotype for laboratory-confirmed HFMD, responsible for 15.6% of severe cases and 1.2% of mild cases. A significant downwards trend of EV-A71 infections was observed after the use of EV-A71 vaccines (P for trend < 0.001). Coxsackievirus A6 was the predominant pathogen, accounting for 63.5% of mild cases and 36.2% of severe cases. Coxsackievirus A10 (CV-A10) and A16 were sporadically detected, and an upwards trend was observed in the proportion of CV-A10 infections. This study provides baseline molecular epidemiology for the evaluation of EV-A71 vaccination impact and potential serotype replacement based on HFMD inpatients. Additional nationwide and population-based epidemiologic and serologic studies are essential to elucidate HFMD dynamics after the use of EV-A71 vaccines, and to inform public health authorities to introduce optimized intervention strategies.

Physically Cross-Linked DNA Hydrogel-Based Sustained Cytokine Delivery for In Situ Diabetic Alveolar Bone Rebuilding.

The development of a biodegradable and shape-adaptable bioscaffold that can enhance local cytokine retention and bioactivity is essential for the application of immunotherapy in periodontal diseases. Here, we report a biodegradable, anti-inflammatory, and osteogenic ILGel that uses a physically cross-linked DNA hydrogel as a soft bioscaffold for the long-term sustained release of cytokine interleukin-10 (IL-10) to accelerate diabetic alveolar bone rebuilding. Porous microstructures of ILGel favored the encapsulation of IL-10 and maintained IL-10 bioactivity for at least 7 days. ILGel can be gradually degraded or hydrolyzed under physiological conditions, avoiding the potential undesired side effects on dental tissues. Long-term sustained release of bioactive IL-10 from ILGel not only promoted M2 macrophage polarization and attenuated periodontal inflammation but also triggered osteogenesis of mesenchymal stem cells (MSCs), leading to accelerated alveolar bone formation and healing of alveolar bone defects under diabetic conditions in vivo. ILGel treatment significantly accelerated the defect healing rate of diabetic alveolar injury up to 93.42 ± 4.6% on day 21 post treatment compared to that of free IL-10 treatment (63.30 ± 7.39%), with improved trabecular architectures. Our findings imply the potential application of the DNA hydrogel as the bioscaffold for cytokine-based immunotherapy in diabetic alveolar bone injury and other periodontal diseases.

[Relationship between acute radiotoxicity and nutritional status of patients with head and neck cancer].

OBJECTIVE: To investigate the relationship between nutritional status and acute radiotoxicity of patients with head and neck cancer. METHODS: Nutritional status and acute radiotoxicities of 130 head and neck cancer patients were prospectively surveyed during the 4th week of radiotherapy. Relationships between nutritional status and acute radiotoxicities were analyzed by canonical correlation. RESULTS: The first canonical correlation coefficient was 0.653, statistically significant, which showed that some negative relationships were found between nutritional status (such as serum prealbumin, transferring, lymphocytes, lymphocyte percentage) and acute radiotoxicities (such as dry mouth, throat/sore throat, fatigue, radiation dermatitis) of head and neck cancer patients. CONCLUSION: When the detection value of serum prealbumin, transferrin, lymphocytes, lymphocyte percentage was below the normal, the appropriate nutritional support would be given to improve immunity and to relieve the acute radiotoxicitoes.

Virus Shedding in Patients With Hand, Foot and Mouth Disease Induced by EV71, CA16 or CA6: Systematic Review and Meta-analysis.

BACKGROUND: As the highly contagious hand, foot and mouth disease (HFMD) spreads rapidly among children, isolation is the most effective way to control its spread. However, studies on the duration of virus shedding of the HFMD-related enterovirus and a reasonable quarantine period for HFMD patients are inconsistent. METHODS: We undertook a systematic review and meta-analysis evaluating the viral shedding of patients with HFMD caused by Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) and coxsackievirus A6. RESULTS: A total of 17 observational studies evaluating 626 participants were included. In the first 5 weeks after onset, the pooled virus positive rate in specimens of EV71-related patients decreased from 0.79 (P < 0.001 for heterogeneity) to 0.38 (P < 0.001 for heterogeneity). The positive rate of CVA16 was reduced from 0.91 (P < 0.001 for heterogeneity) to 0.29 (P < 0.001 for heterogeneity). The positive rates of CVA16 and coxsackievirus A6 were approximately 50% in the third week after onset, while a 50% positive rate appeared in the fourth week in EV71 related cases. CONCLUSIONS: We found the positive rates of virus shedding were still high among the patients released from quarantine, and the duration of viral shedding was inconsistent among HFMD patients caused by different serotypes. Our findings provide comprehensive evidence for a possible flexible quarantine period according to the serotype.

The study of improved controlled release of vincristine sulfate from collagen-chitosan complex film.

A water-in-oil-in-oil double-emulsion solvent/evaporation method was used to prepare vincristine sulfate (VCR) loaded poly(lactide-co-glycolide) microspheres, and then VCR microspheres were mixed with collagen and (or) chitosan swelling solution and lyophilized to form polymeric films. The films were cross-linked by 0.3% glutaraldehyde (GA). Encapsulation efficiency and release kinetics of VCR microspheres were determined, as well as release kinetics and in vitro degradation of the film. The rate of VCR release from the film submerged in PBS (pH 6.8) and the content were measured by high-performance liquid chromatography (HPLC). The physichemical properties of the film, such as surface morphology, mechanical function, and differential scanning calorimetry, were also measured. VCR was released from the film in a prolonged period and the initial burst release of the film was less significant. In the degradation experiment, the film containing chitosan degraded more slowly than that without chitosan. The films comprising collagen and chitosan could achieve the release kinectics of a relatively constant release. It has a promising future.

Anticoagulant polyurethane substrates modified with poly(2-methacryloyloxyethyl phosphorylcholine) via SI-RATRP.

A novel catalyst system of Reverse Atom Transfer Radical Polymerization (RATRP) to prepare Polyurethane (PU) films modified by poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC) was studied in this article. In this system, PU film was pretreated by LaCl3/CA ethanol solution to obtain a hydrated surface allowing more initiators to be immobilized on it. Moreover, complexes composed of silane coupling agent 3-chloropropyltrimethoxysilane (CPTM), chlorhexidine acetate (CA) and lanthanum(III) worked as ligands of copper ions as a whole during RATRP process. PU films before and after modification were characterized by X-ray photoelectron spectroscopy (XPS) and static contact angle (SCA) to confirm that pMPC chains were successfully grafted from the substrates. Results of Plasma recalcification time assay, platelet adhesion test indicated excellent blood compatibility. Furthermore, the antibacterial activity of the material have been improved which proved by adhesion test of E.coil.

Comparative efficacy of combination of 1 L polyethylene glycol, castor oil and ascorbic acid versus 2 L polyethylene glycol plus castor oil versus 3 L polyethylene glycol for colon cleansing before colonoscopy: Study protocol of a randomized, double-blind, single-center study.

Colonoscopy has been regarded as an important method of early diagnosing and treating gastrointestinal lesions; however adequate bowel preparation is critical one of many factors needed for successful colonoscopy. Although several modified or novel regimes have been developed, desired quality of bowel preparation has not yet been generated. Scattered evidences revealed that castor oil may have potential of effectively cleansing colon. It is noted that, however, prospective trial of exploring the value of castor oil in preparing bowel before colonoscopy is lacking. The aims of this study are to test the hypotheses that low dose castor oil (30 mL) may enhance potential of polyethylene glycol (PEG) and combination of low castor oil and ascorbic acid may halve the volume of PEG.This is a randomized, double-blind (endoscopist and assessor), single center trial with three-arm design. We will randomly assign 282 adult patients (≥18 years but < 75 years), who are scheduled to undergo colonoscopy, to receive either 3 L PEG alone, 2 L PEG plus 30 mL castor oil or combination of 1 L PEG, 30 mL castor oil and 5 g ascorbic acid. The bowel preparation quality based on Boston Bowel Preparation Scale (BBPS) is the primary outcome. The secondary outcomes include the first defecation time, total number of defecation, time of cecal intubation, detection rate of polyp and adenoma, willing to repeat the same regime, tolerance to regime, and adverse events.The study protocol has been approved by the Clinical Research Ethics Committees of Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital & Chongqing Cancer Center (2017[107]). The results from this trial will be submitted for publication in peer-reviewed journals, and will be presented at national and international conferences.

Comparative efficacy of low volume versus traditional standard volume PEG on bowel preparation before colonoscopy: Protocol for an updated meta-analysis with trial sequential analysis.

INTRODUCTION: Polyethylene glycol (PEG) has been considered as the first recommendation for bowel preparation prior to colonoscopy. A previous meta-analysis suggested that low volume PEG may improve the acceptability of ingesting bowel preparation solution. However, several limitations impaired the power of findings from this published meta-analysis, such as the variation in study design of included trials and adjuvant prescriptions. Moreover, some studies related to this topic have been published recently. And thus, the aim of this updated meta-analysis is to further assess the comparative efficacy of low volume versus standard volume of PEG on bowel preparation before colonoscopy with trial sequential analysis (TSA). METHODS AND ANALYSIS: Systematic searches will be performed to capture any potential randomized controlled trials (RCTs) investigated the comparative efficacy of low volume versus traditional standard volume PEG on bowel preparation prior to colonoscopy in PubMed, EMBASE, and Cochrane Central Register of Controlled Trials. Moreover, we will also manually check the bibliographies of related studies and reviews so as to get additional studies. Two reviewers will independently screen the citation records, extract essential information, and appraise the risk of bias of each RCT in sequence. Finally, we will used the STATA software version 12.0 and TSA software version beta 0.9 to statistically analyze all data and test the robust of each pooled result, respectively. RESULTS: We will submit the full-text of systematic review to a peer-review journal for publication. CONCLUSION: This updated systematic review and meta-analysis with TSA will further assess the comparative efficacy and safety of low-volume versus traditional standard volume PEG for bowel preparation prior to colonoscopy. And then, a more comprehensive evidence body on low-volume compared to standard volume PEG in bowel preparation will be constructed.

[Preparation and characterization of vincristine sulfate-loaded PLGA microspheres].

OBJECTIVE: To prepare the vincristine sulfate (VCR) microspheres by W/O/O solvent evaparation method and evaluate the effect of zinc carbonate (ZnCO3) on the morphology and release kinetics of the microspheres. METHODS: Degradation kinetic of VCR was tested in PBS of four different pH values at 37TC to select the optimal incubation medium for in vitro release. Microspheres were made with or without Zn-CO3 (w/w 5% and 10%) in the polymeric phase. The properties and in vitro release profiles of the microspheres were examed. RESULTS: ZnCO3 increased the stability of VCR in the PLGA microspheres. During the 36 days of in vitro release, the accumulative release of VCR from the microspheres reached > 70% when added with ZnCO3, and was (54.2 +/- 1.1)% when no ZnCO3 was added. 10% ZnCO3 showed superior effect than 5% ZnCO3 in the stabilization of microspheres. CONCLUSIONS: Adding ZnCO3 is essential during the preparation of PLGA microspheres. It can remarkably improve the stability of drugs in the acid microenvironment inside PL-GA microspheres and decrease the VCR degradation during incubation.

Cationic Polystyrene Resolves Nonalcoholic Steatohepatitis, Obesity, and Metabolic Disorders by Promoting Eubiosis of Gut Microbiota and Decreasing Endotoxemia.

A pandemic of metabolic diseases, consisting of type 2 diabetes, nonalcoholic fatty liver disease, and obesity, has imposed critical challenges for societies worldwide, prompting investigation of underlying mechanisms and exploration of low-cost and effective treatment. In this report, we demonstrate that metabolic disorders in mice generated by feeding with a high-fat diet without dietary vitamin D can be prevented by oral administration of polycationic amine resin. Oral administration of cholestyramine, but not the control uncharged polystyrene, was able to sequester negatively charged bacterial endotoxin in the gut, leading to 1) reduced plasma endotoxin levels, 2) resolved systemic inflammation and hepatic steatohepatitis, and 3) improved insulin sensitivity. Gut dysbiosis, characterized as an increase of the phylum Firmicutes and a decrease of Bacteroidetes and Akkermansia muciniphila, was fully corrected by cholestyramine, indicating that the negatively charged components in the gut are critical for the dysbiosis. Furthermore, fecal bacteria transplant, derived from cholestyramine-treated animals, was sufficient to antagonize the metabolic disorders of the recipient mice. These results indicate that the negatively charged components produced by dysbiosis are critical for biogenesis of metabolic disorders and also show a potential application of cationic polystyrene to treat metabolic disorders through promoting gut eubiosis.