Fecal microbiota transplantation for treatment of non-alcoholic fatty liver disease: Mechanism, clinical evidence, and prospect.

The population of non-alcoholic fatty liver disease (NAFLD) patients along with relevant advanced liver disease is projected to continue growing, because currently no medications are approved for treatment. Fecal microbiota transplantation (FMT) is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease. There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment, however, existing findings diverge on its effects. Herein, we briefly summarized the mechanism of FMT for NAFLD treatment, reviewed randomized controlled trials for evaluating its efficacy in NAFLD, and proposed the prospect of future trials on FMT.

Novel practical stereoselective synthesis of a bicyclic hydantoino-thiolactone as the key intermediate for production of (+)-biotin.

Bicyclic hydantoinothiolactone (1), as the key intermediate for production of (+)-biotin, has been efficiently and high-stereoselectively synthesized from the cheap starting material l-cystine via nine steps in 44% overall yield. In this new practical synthesis, there are two characteristic steps worthy of note. One step is TMSOTf-catalyzed efficient cyanation of (3S,7aR)-6-benzyl-5-oxo-3-phenyltetrahydro-1H,3H-imidazo[1,5-c]thiazol-7-yl acetate, the other step is DBU-catalyzed rapid isomerization of trans-isomer to cis-isomer of the bicyclic hydantoinothiolactone.

Kinesiophobia and related factors in cancer patients with TIAPs during the long term: a cross-sectional survey.

OBJECTIVE: This study is designed to investigate the status of kinesiophobia and related factors in cancer patients with totally implantable venous access ports (TIAPs). METHODS: This is a cross-sectional study; all the participants were recruited from the Oncology Department and the Daytime Chemotherapy Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine, from April 1 to May 31, 2021. The participants were interviewed by researchers using the self-made general information questionnaire and the Tampa Scale of Kinesiophobia-11 (TSK-11) scale, which allows the fear of movement to be quantified. Eligible patients were aged ≥ 18 years, confirmed with cancer, and implanted with a port. The logistic regression model was used to evaluate clinical factors and the risk of kinesiophobia. RESULTS: A total of 282 patients were recruited (aged 58.0 ± 11.5 years), of which gastrointestinal cancer accounted for 54.6%, breast cancer accounted for 22.7%, lung cancer accounted for 11.3%, and other types accounted for 11.3%. The TSK-11 score of the 282 patients was 17.84 ± 6.06 points, 45.7% of the patients reported mild kinesiophobia (TSK-11 ≥ 18), 18.4% of the patients reported moderate to severe kinesiophobia (TSK-11 ≥ 25), and the highest score reached 34 points. Results of logistic regression analysis showed that exercise habits (P = 0.025), pain (P = 0.023), and foreign body sensation (P = 0.003) were the risk factors of kinesiophobia. CONCLUSION: Kinesiophobia is common in cancer patients with TIAPs, and it is closely related to the subjective experience of daily activities, which requires more attention and early intervention to reduce the potential adverse effects.

Puerarin ameliorated pressure overload-induced cardiac hypertrophy in ovariectomized rats through activation of the PPARα/PGC-1 pathway.

Estrogen deficiency induces cardiac dysfunction and increases the risk of cardiovascular disease in postmenopausal women and in those who underwent bilateral oophorectomy. Previous evidence suggests that puerarin, a phytoestrogen, exerts beneficial effects on cardiac function in patients with cardiac hypertrophy. In this study, we investigated whether puerarin could prevent cardiac hypertrophy and remodeling in ovariectomized, aortic-banded rats. Female SD rats subjected to bilateral ovariectomy (OVX) plus abdominal aortic constriction (AAC). The rats were treated with puerarin (50 mg·kg-1 ·d-1, ip) for 8 weeks. Then echocardiography was assessed, and the rats were sacrificed, their heart tissues were extracted and allocated for further experiments. We showed that puerarin administration significantly attenuated cardiac hypertrophy and remodeling in AAC-treated OVX rats, which could be attributed to activation of PPARα/PPARγ coactivator-1 (PGC-1) pathway. Puerarin administration significantly increased the expression of estrogen-related receptor α, nuclear respiratory factor 1, and mitochondrial transcription factor A in hearts. Moreover, puerarin administration regulated the expression of metabolic genes in AAC-treated OVX rats. Hypertrophic changes could be induced in neonatal rat cardiomyocytes (NRCM) in vitro by treatment with angiotensin II (Ang II, 1 µM), which was attenuated by co-treatemnt with puerarin (100 µM). We further showed that puerarin decreased Ang II-induced accumulation of non-esterified fatty acids (NEFAs) and deletion of ATP, attenuated the Ang II-induced dissipation of the mitochondrial membrane potential, and improved the mitochondrial dysfunction in NRCM. Furthermore, addition of PPARα antagonist GW6471 (10 µM) partially abolished the anti-hypertrophic effects and metabolic effects of puerarin in NRCM. In conclusion, puerarin prevents cardiac hypertrophy in AAC-treated OVX rats through activation of PPARα/PGC-1 pathway and regulation of energy metabolism remodeling. This may provide a new approach to prevent the development of heart failure in postmenopausal women.

Intestinal dysbiosis in pediatric Crohn's disease patients with IL10RA mutations.

BACKGROUND: Several studies have employed animal models to explore the association between microbiota and interleukin (IL) 10 signaling; however, limited information is available about the human microbiome. AIM: To characterize the microbiome in patients with IL10RA mutations and to explore the association between gut dysbiosis and disease severity. METHODS: Fecal samples were collected from patients who were diagnosed with loss-of-function mutations in the IL10RA gene between January 2017 and July 2018 at the Children's Hospital of Fudan University. Age-matched volunteer children were recruited as healthy controls. Patients with Crohn's disease (CD) were used as disease controls to standardize the antibiotic exposure. Microbial DNA was extracted from the fecal samples. All analyses were based on the 16S rRNA gene sequencing data. RESULTS: Seventeen patients with IL10RA mutations (IL10RA group), 17 patients with pediatric CD, and 26 healthy children were included. Both patients with IL10RA mutations and those with CD exhibited a reduced diversity of gut microbiome with increased variability. The relative abundance of Firmicutes was substantially increased in the IL10RA group (P = 0.02). On further comparison of the relative abundance of taxa between patients with IL10RA mutations and healthy children, 13 taxa showed significant differences. The IL10RA-specific dysbiosis indices exhibited a significant positive correlation with weighted pediatric CD activity index and simple endoscopic score for CD. CONCLUSION: In patients with IL10RA mutations and early onset inflammatory bowel disease, gut dysbiosis shows a moderate association with disease severity.

Carvacrol protects against diabetes-induced hypercontractility in the aorta through activation of the PI3K/Akt pathway.

Vascular complications induced by diabetes constitute the principal cause of morbidity and mortality in diabetic patients. It has been reported that carvacrol (CAR) possesses a wide range of biological activities. The effects of CAR on diabetes-induced vasculopathy remain unknown. In this study, diabetic mice were created by the intraperitoneal injection of streptozotocin (STZ) in male C57BL/6 J mice to investigate whether CAR provided a protective effect against diabetes-induced vasculopathy and to investigate the underlying mechanisms. We found that CAR decreased blood glucose levels in diabetic mice. Moreover, CAR ameliorated diabetes-induced aortic morphological alterations, as evidenced by an increased thickness in the intima-media width and an increased number of vascular smooth muscle cells (VSMCs) layers. Further studies revealed that CAR inhibited hypercontractility in the aortas of diabetic mice and VSMCs in response to hyperglycemia, as evidenced by the relaxation of phenylephrine(PE)-induced vasoconstriction, the decreased expression of smooth muscle (SM)-α-actin, and the increased expression of Ki67 and proliferating cell nuclear antigen (PCNA). Furthermore, the PI3K/Akt signaling pathway was inhibited in the aortas of diabetic mice and VSMCs in response to hyperglycemia, while CAR treatment activated the PI3K/Akt signaling pathway. In conclusion, our results strongly suggest that CAR plays a protective role in diabetes-induced aortic hypercontractility, possibly by activating the PI3K/Akt signaling pathway. CAR is a potential drug for the treatment of diabetic vasculopathy.

[Finite-element analysis of mandibular first molar with two marginal designs of endocrown for the repair of different defects].

OBJECTIVE: This study aimed to evaluate the stress distribution of the mandibular first molar with different thicknesses and heights of the axial wall restored by the endocrown with two marginal designs and thus provide a theoretical basis for selecting clinical preparation through the finite-element method. METHODS: Two marginal endocrowns of the mandibular first molar with different axial-wall thicknesses (t=1, 2, 3 mm) and heights (h=2, 3, 4 mm) were established. Group A was the butt-joint design, whereas group B was the shoulder-surrounded design. After applying vertical and oblique loads , the size and distribution of the maximum principal stress and equivalent stress of residual tooth tissue were recorded. RESULTS: The maximum principal stress and equivalent stress distribution of residual tooth tissue were similar among different models. Group A showed a lower maximum principal stress and equivalent stress than group B at the same thickness and height under vertical load. Meanwhile, under oblique load, the maximum principal stress values of groups A and B decreased with increased thickness at constant height. Group A showed lower equivalent stress than group B at the same thickness and height of 2 and 3 mm. However, when the height was 4 mm, the trend was reversed. CONCLUSIONS: In mastication, when bearing the vertical force, the retention of the butt-joint marginal endocrown preferred to the shoulder-surrounded one. Given the higher axial wall of the shoulder-surrounded marginal endocrown, it showed better ability to bear the oblique force than the butt-joint one.

Special clinical characteristics and outcomes in Chinese pediatric patients with early-onset Crohn's disease.

OBJECTIVE: To study the clinical and nutritional characteristics of early-onset Crohn's disease (EO-CD) in China. METHODS: Patients were defined as having EO-CD (age at diagnosis <10 y) or late-onset Crohn's disease (LO-CD; age at diagnosis of 10-17 y). Their characteristics, clinical, and nutritional data were collected at baseline and at each follow-up visit. Statistical analyses were used to compare differences in both groups. RESULTS: From July 1993 to February 2017, of the 137 children enrolled, 68 (49.6%) had EO-CD and 69 (50.4%) had LO-CD. More patients with EO-CD than those with LO-CD presented with diarrhea, hematochezia, growth delay, anemia and skin disease, and had higher pediatric Crohn's disease activity index scores at diagnosis (all P < 0.05). Fewer patients with EO-CD achieved their first remission (42.6% vs 76.8%, P < 0.0001) during follow-up. Patients with EO-CD required a longer treatment time to reach remission (P = 0.0049) and had a higher mortality rate (P = 0.0133), as well as lower height and weight percentiles (P = 0.0200 and 0.0288, respectively), hemoglobin (P = 0.0185) and albumin levels (P = 0.0002), zinc (P = 0.0024) and iron (P = 0.0110) concentrations in blood at diagnosis. CONCLUSION: The EO-CD group had worse clinical outcomes and nutritional status than the LO-CD group.

Nitazoxanide, an anti-parasitic drug, efficiently ameliorates learning and memory impairments in AD model mice.

The pathogenesis of Alzheimer's disease (AD) is characterized by both accumulation of ß-amyloid (Aß) plaque and formation of neurofibrillary tangles in the brain. Recent evidence shows that autophagy activation may potently promote intracellular Aß clearance. Thus targeting autophagy becomes a promising strategy for discovery of drug leads against AD. In the present study, we established a platform to discover autophagy stimulator and screened the lab in-house FDA-approved drug library. We found that anti-parasitic drug nitazoxanide (NTZ) was an autophagy activator and could efficiently improve learning and memory impairments in APP/PS1 transgenic mice. In BV2 cells and primary cortical astrocytes, NTZ stimulated autophagy and promoted Aß clearance by inhibiting both PI3K/AKT/mTOR/ULK1 and NQO1/mTOR/ULK1 signaling pathways; NTZ treatment attenuated LPS-induced inflammation by inhibiting PI3K/AKT/IκB/NFκB signaling. In SH-SY5Y cells and primary cortical neurons, NTZ treatment restrained tau hyperphosphorylation through inhibition of PI3K/AKT/GSK3ß pathway. The beneficial effects and related signaling mechanisms from the in vitro studies were also observed in APP/PS1 transgenic mice following administration of NTZ (90 mg·kg-1·d-1, ig) for 100 days. Furthermore, NTZ administration decreased Aß level and senile plaque formation in the hippocampus and cerebral cortex of APP/PS1 transgenic mice, and improved learning and memory impairments in Morris water maze assay. In conclusion, our results highlight the potential of NTZ in the treatment of AD.

A Novel α2-Globin Gene Mutation: Hb Debao [α31(B12)Arg→Trp; HBA2: c.94A>T].

We report a novel mutation on the α2-globin gene, Hb Debao [α31(B12)Arg→Trp; HBA2: c.94A>T] detected in a Chinese family. This mutation gives rise to a previously undescribed hemoglobin (Hb) variant that was undetectable by electrophoretic or chromatographic methods. Hb Debao was associated with an α+-thalassemia (α+-thal) deletion [-α3.7 (rightward)] producing a mild phenotype with significant microcytosis and hypochromia, while the combination of this mutation with an α0-thal deletion (--SEA) resulting in a severe form of Hb H (ß4) disease, which is consistent with a thalassemic phenotype associated with the novel mutation.

[Influence of different restorations on the fracture resistance of endodontically treated premolars with minor loss of dental defect].

PURPOSE: To evaluate the influence of 3 different restorations on the fracture resistance of endodontically treated premolars with minor loss of dental defect in order to direct clinical design. METHODS: Seventy-two recently extracted intact and single-rooted human mandibular premolars for orthodontic reason were collected and randomly divided into 3 groups (group A, B, C, n=24). Each group was respectively prepared into 1/3 defect of occlusal surface (group A), 1/2 defect of occlusal surface (group B) and 1/3 defect of proximal-occlusal surface model (group C). Then each group was divided into 3 subgroups with one restored with a light-curing composite resin(group A1, B1, C1), one restored with cast metal full crowns following a light-curing composite resin (group A2, B2, C2), and one restored with fiber posts and resin cores and cast full crowns after teeth preparations (group A3, B3, C3, n=8). Static loading tests were performed on each specimen until cracked.Fracture strength was tested and fracture patterns were examined. The data was analyzed using SPSS17.0 software package. RESULTS: The fracture resistance of subgroup A2 was different when compared with subgroup A1 and subgroup A3. In group B and C, the fracture resistance of teeth in subgroup B2, B3, C2 and C3 were significantly higher than that in subgroup B1 and C1. There was no significant difference in the fracture mode of 3 restorations in group A, B and C. CONCLUSIONS: A composite resin combined with cast metal full crowns can be used as the first choice to restore endodontically treated premolars with proximal-occlusal 1/3 defects and occlusal defects that do not surpass 1/2 dimension of occlusion.

[Finite element analysis of the angulation designment of implant planning in the anterior maxilla].

PURPOSE: To provide theoretical reference for maxillary anterior restoration designment in clinics by observing the masticatory stress distribution of the implant-bone interface and the displacement of implant. METHODS: This study built simplified 3 dimensional finite models with different angles, which included partial implant (4.3 mm×11.5 mm), abutment and all ceramic crown (Zirconia) and combined with angle of implant A between the long axis of ideal implant and factual implant (0°, 5°, 10°, 15°, 20°, 25°), as well as angle of abutment B between the long axis of abutment and implant (0°, 5°,10°,15°,20°,25°). A force load of 178 N was applied 2 mm below the incisal edge on the palatal surface of the crown, with an approximately 130° angle to the long axis of the crown. The displacement of implant maximum principal stress value and distribution of the implant-bone interface were determined by using Ansys 13.0 software. RESULTS: Sixteen 3-dimensional models of different implant restoration plan of implant dentures of maxillary incisor were built. When the angle of abutment was increasing with the same labial inclination of implant, the objective functions were enhanced. When the labial inclination of implant was increasing with the same angle of abutment, the objective functions were also improved. With the change of labial inclination of implant and angled abutment, the labial inclination of implant concentrated more than the angle of abutment on the objective functions. When the angle of abutment was between 0 degree and 20 degree, the amplitude of all the objective functions were gentle, while the labial inclination of implant and amplitude of all the objective functions were increased when the angle of abutment increased to 25 degree. CONCLUSIONS: A positive correlation is found between the value of stress of the bone around the implant, and the displacement of implant and the labial inclination of the implant and the angle of abutment. It is necessary to decrease the labial inclination of the implant and the angle of abutment, especially strictly control the labial inclination of the implant. Taking the stress and displacement into consideration, both of two angles ranging from 0 degree to 20 degree are the best optimal choice for the anterior implants. When both of two angles increase to much greater than 20 degree, the value of stress increase remarkably, which will decrease the chance of successful implant.

Incidence, risk factors and clinical outcomes of peripherally inserted central catheter spontaneous dislodgment in oncology patients: a prospective cohort study.

PURPOSE: Peripherally inserted central catheter (PICC) spontaneous dislodgment is insidious in onset and prone to cause complications. We performed a prospective cohort study to examine the incidence, risk factors and clinical results of PICC spontaneous dislodgment in oncology patients to facilitate successful early diagnosis, prophylaxis and management. PATIENTS AND METHODS: Consecutive oncology patients, undergoing placement of PICCs, were enrolled and prospectively followed up until their catheters were removed or PICC spontaneous dislodgment presented. The patients with PICC spontaneous dislodgment or catheter-associated thrombosis (CRT) were followed up for an extra three months from the date of diagnosis. The main endpoint was PICC spontaneous dislodgment, and the sub-endpoints were CRT and catheter in-place time. The PICC insertion team, nurses, interventional radiologists and oncology doctors collected longitudinal data. RESULTS: Over a total of 60,894 days of cumulative follow-up, 21 out of 510 PICCs presented spontaneous dislodgment, leading to an incidence rate of 4.12%. The CRT rate of the group with PICC spontaneous dislodgment was much higher than that of the group without PICC spontaneous dislodgment (RR=17.46, 95% CI: 8.29-36.82, p=1.09×10(-17)). Five baseline exposure factors, including primary lung cancer, metastatic lung cancer, chest radiotherapy, vigorous coughing and severe vomiting, were significant risk factors of PICC spontaneous dislodgment. Basilic vein access (odds ratio [OR]=0.39, 95% CI: 0.16-0.95, P=0.04) was a protective factor against PICCSD in univariate analysis. Among these factors, the independent significant risk factors were vigorous coughing (OR=6.14, 95% CI: 1.70-22.16, P=0.01) and severe vomiting (OR=3.70, 95% CI: 1.28-10.68, P=0.02). CONCLUSION: The incidence rate of PICC spontaneous dislodgment is 4.12% (0.34 per 1000 catheter-days); PICC spontaneous dislodgment significantly increases the risk of CRT and shortens catheter in-place time. Vigorous coughing and severe vomiting were independent risk factors of PICC spontaneous dislodgment among oncology patients.

[Three-dimensional finite element stress analysis of mandibular first molar with single and combined crowns after separation prosthodontic therapy].

PURPOSE: To evaluate the influence of two kinds of fixed prosthesis on the stress of the mandibular first molar with separation prosthodontic therapy. METHODS: A 3-D finite element model of the mandibular first molar was established with single and combined crowns and their supporting tissues by means of cone-beam CT (CBCT) scanning technology and software Mimics, Geomagic, UG of image processing program. Under dispersed vertical load and dispersed oblique load, the stresses of dental tissues and periodontium were obtained and analysed. RESULTS: When dispersed vertical load was applied, the dental and periodontal stress distribution of two models were similar to the normal. The dental stress value and maximum tensile stress of the periodontal membrane increased and changed greatly in the single crown. When dispersed oblique load was applied, the model of combined crown was similar to the normal. The stress concentrated area expanded in the distal root of the single crown model and the buccal bottom half of the periodontium. The dental stress value and maximum tensile stress of the periodontal membrane increased and changed greatly in the single crown. CONCLUSIONS: The combined crown is a better choice for restoration of mandibular first molar after separation prosthodontic therapy.

Relationship between alcohol drinking and alcohol-related health problems.

OBJECTIVE: To study the relationship between drinking environment, attitudes and situation and alcohol-related health problems. METHODS: A sample of 2327 respondents was randomly collected from Wuhan, Hubei Province in China by a face-to-face interview. The structural equation modeling analysis was performed for the data collected. RESULTS: Both parents' drinking behaviors and respondents' drinking situation strongly impacted the alcohol-related problems and diseases. Friends' or peers' drinking behaviors influenced the respondents' drinking attitudes and behaviors. Males experienced more alcohol-related problems and diseases than females. CONCLUSIONS: Comparatively, parents' drinking behaviors exert the most significant influence on drinkers. Therefore, it is beneficial to restrict parents' drinking behaviors for the offsprings and the whole society, and an intensive professional education in early motherhood is also necessary for Chinese women.