The gut microbiota regulates intestinal nutrient absorption, participates in modulating host glucolipid metabolism, and contributes to ameliorating glucolipid metabolism disorder. Dysbiosis of the gut microbiota can compromise the integrity of the intestinal mucosal barrier, induce inflammatory responses, and exacerbate insulin resistance and abnormal lipid metabolism in the host. Dangua Humai Oral Liquid, a hospital-developed formulation for regulating glucolipid metabolism, has been granted a national invention patent and demonstrates significant clinical efficacy. This study aimed to investigate the effects of Dangua Humai Oral Liquid on gut microbiota and the intestinal mucosal barrier in a mouse model with glucolipid metabolism disorder. A glucolipid metabolism disorder model was established by feeding mice a high-glucose and high-fat diet. The mice were divided into a normal group, a model group, and a treatment group, with eight mice in each group. The treatment group received a daily gavage of Dangua Humai Oral Liquid(20 g·kg~(-1)), while the normal group and model group were given an equivalent volume of sterile water. After 15 weeks of intervention, glucolipid metabolism, intestinal mucosal barrier function, and inflammatory responses were evaluated. Metagenomics and untargeted metabolomics were employed to analyze changes in gut microbiota and associated metabolic pathways. Significant differences were observed between the indicators of the normal group and the model group. Compared with the model group, the treatment group exhibited marked improvements in glucolipid metabolism disorder, alleviated pathological damage in the liver and small intestine tissue, elevated expression of recombinant claudin 1(CLDN1), occluding(OCLN), and zonula occludens 1(ZO-1) in the small intestine tissue, and reduced serum levels of inflammatory factors lipopolysaccharides(LPS), lipopolysaccharide-binding protein(LBP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). At the phylum level, the relative abundance of Bacteroidota decreased, while that of Firmicutes increased. Lipid-related metabolic pathways were significantly altered. In conclusion, based on the successful establishment of the mouse model of glucolipid metabolism disorder, this study confirmed that Dangua Humai Oral Liquid effectively modulates gut microbiota and mucosal barrier function, reduces serum inflammatory factor levels, and regulates lipid-related metabolic pathways, thereby ameliorating glucolipid metabolism disorder.
Animals ; Gastrointestinal Microbiome/drug effects* ; Mice ; Intestinal Mucosa/microbiology* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL ; Humans ; Glycolipids/metabolism* ; Lipid Metabolism/drug effects* ; Administration, Oral ; Disease Models, Animal

Objective:To explore any effect of on the limb and cardiopulmonary functioning of stroke survivors of combining new Bobath technique with cardiopulmonary rehabilitation.Methods:A total of 160 stroke survivors with limb disorders were randomly divided into an observation group and a control group, each of 80. Both groups were given routine rehabilitation and the new version of Bobath training, but the observation group was additionally provided with 12 weeks of cardiopulmonary rehabilitation. Before and after the treatment the limb functioning of both groups was evaluated along with their ability in the activities of daily living and the recovery of damaged nerve function, using the simplified Fugl-Meyer (FMA) motor function scoring, the modified Barthel index (MBI) and the Chinese stroke scale (CSS). Peak oxygen uptake (VO 2peak), peak metabolic equivalent (METpeak), peak heart rate (HRpeak) and anaerobic thresholds (ATs) were documented. Results:After the treatment the average FMA, MBI and CSS scores and cardiopulmonary indexes had improved significantly in both groups. All were then significantly better in the observation group than in the control group.Conclusions:Combining the new Bobath technique with cardiopulmonary rehabilitation can significantly improve the limb and cardiopulmonary functioning of stroke survivors, as well as their skill in the activities of daily living and the recovery of the damaged nerve functionality. This combination is therefore worthy of clinical promotion and application.

Hepatotoxicity is a common side effect for patients treated with gefitinib, but the related pathogenesis is unclear and lacks effective predictor and management strategies. A multi-omics approach integrating pharmacometabolomics, pharmacokinetics and pharmacogenomics was employed in non-small cell lung cancer patients to identify the effective predictor for gefitinib-induced hepatotoxicity and explore optional therapy substitution. Here, we found that patients with rs4946935 AA, located in Forkhead Box O3 (FOXO3) which is a well-known autophagic regulator, had a higher risk of hepatotoxicity than those with the GA or GG variant (OR = 18.020, 95%CI = 2.473 to 459.1784, P = 0.018) in a gefitinib-concentration dependent pattern. Furthermore, functional experiments identified that rs4946935_A impaired the expression of FOXO3 by inhibiting the promotor activity, increasing the threshold of autophagy initiation and inhibiting the autophagic activity which contributed to gefitinib-induced liver injury. In contrast, erlotinib-induced liver injury was independent on the variant and expression levels of FOXO3. This study reveals that FOXO3 mutation, leading to autophagic imbalance, plays important role in gefitinib-induced hepatotoxicity, especially for patients with high concentration of gefitinib. In conclusion, FOXO3 mutation is an effective predictor and erlotinib might be an appropriately and well-tolerated treatment option for patients carrying rs4946935 AA.

Objective To explore the effect of repeated transcranial magnetic stimulation ( rTMS) com-bined with rehabilitation training on the motor and non-motor symptoms of Parkinson's disease. Methods A total of 150 persons with Parkinson's disease were randomly divided into an rTMS group, a rehabilitation training group and an observation group, each of 50. The rTMS group received only repeated magnetic stimulation. The rehabilita-tion training group received only standard rehabilitation training. The observation group was given both for 4 weeks. The overall efficacy of each treatment was evaluated using the unified Parkinson's disease rating scale ( UPDRS) , while the motor symptoms were assessed using the 10 m back-and-forth run test, a simple test for evaluating hand function ( STEF) and Berg's balance scale. Non-motor symptoms were evaluated using a questionnaire ( NMSQ) , the mini-mental state examination ( MMSE) , the Hamilton depression scale ( HAMD) , the Hamilton anxiety scale ( HAMA) and the Parkinson's disease sleep scale ( PDSS) . Moreover, a comprehensive quality of life assessment questionnaire ( SF-36) was used to evaluate the life quality of patients before and after the treatment. Results Compared with before the treatment, the average UPDRS scores of all three groups were lower after the treatment. Moreover, the average UPDRS score of the observation group was significantly lower than those of the other two groups. Significant improvement was observed in the mean 10 m run time and in the average STEF and Berg scores of the rehabilitation training and observation groups, but not in the rTMS group's averages. After the treatment, the mean NMSQ, MMSE, HAMD, HAMA and PDSS results of the rTMS and observation groups were significantly bet-ter than those before treatment, with the observation group's averages significantly better than those of the rehabili-tation training group. The average PDSS and SF-36 scores of the observation group were also significantly better than those of the other groups. Conclusion rTMS combined with rehabilitation training can significantly improve the motor and non-motor symptoms of Parkinson's disease patients, and its efficacy is superior to that of rTMS or reha-bilitation training alone.

Objective To observe the effect of injecting botulinum toxin type A on muscle tension,disability level and ability in the activities of daily living in patients with post-stroke dystonia.Methods Thirty-two patients with post-stroke dystonia were divided into an observation group (n =16) and a control group (n =15).The patients in the observation group were injected with 200-600 U of botulinum toxin type A in the relevant muscles,while the patients in the control group were given 12 mg diphenhydrazole hydrochloride tablets orally.Before and 2,6 and 12 weeks after the treatment,spasticity,disability and daily living ability were evaluated in both groups using the modified Ashworth scale (MAS),a disability assessment scale (DAS) and the modified Barthel index (MBI).Results After the treatment,the average MAS,DAS and MBI scores of both groups were significantly better than before the treatment.And the average MAS,DAS and MBI scores of the observation group were significantly better than those of the control group.Conclusion Botulinum toxin A injection can significantly improve dystonia and relieve disability among stroke survivors.

OBJECTIVETo summarize the clinical characteristics of peripheral blood, immune phenotypes, fusion genes and cytogenetics of patients with t(8;21) acute myeloid leukemia(AML) through the retrospective analysis of 586 patients with t(8;21) AML from 15 blood disease research centers in Northern area of China.

METHODSThe factors affecting prognosis of patients with t(8;21) AML were investigated by using univariate and multivariate COX regression.

RESULTSThe immune type of t(8;21) AML patients was mainly with HLA-DR, CD117, CD34, MPO, CD38, CD13and CD33(>95%), part of them with CD19and CD56; the most common accompanied mutation of t(8;21) AML patients was C-KIT mutation (37.8%); in addition to t(8;21) ectopic, the most common chromosomal abnormality was sex chromosome deletions (38.9%). The univariate analysis revealed a significant survival superiority of OS and PFS in t(8;21) AML patients of WBC≤3.5×10/L without C-KIT mutation, the newly diagnosed ones achieved HSCT(P<0.05), only survival superiority on OS in t(8;21) AML patients with extramedullary infiltration and CD19 positive; the results of multivariate analysis showed a significant survival superiority on OS and PFS in t(8;21) AML patients with WBC≤3.5×10/L(P<0.05).

CONCLUSIONThe clinical features of t(8;21) AML patients in China are similar to those in other countries, WBC≤3.5×10/L is a good prognostic factor while the C-KIT mutation is a poor one in t(8;21) AML patients.

Formation of biofilm is a survival strategy for bacteria and fungi to adapt to their living environment, especially in the hostile environment. Under the protection of biofilm, microbial cells in biofilm become tolerant and resistant to antibiotics and the immune responses, which increases the difficulties for the clinical treatment of biofilm infections. Clinical and laboratory investigations demonstrated a perspicuous correlation between biofilm infection and medical foreign bodies or indwelling devices. Clinical observations and experimental studies indicated clearly that antibiotic treatment alone is in most cases insufficient to eradicate biofilm infections. Therefore, to effectively treat biofilm infections with currently available antibiotics and evaluate the outcomes become important and urgent for clinicians. The review summarizes the latest progress in treatment of clinical biofilm infections and scientific investigations, discusses the diagnosis and treatment of different biofilm infections and introduces the promising laboratory progress, which may contribute to prevention or cure of biofilm infections. We conclude that, an efficient treatment of biofilm infections needs a well-established multidisciplinary collaboration, which includes removal of the infected foreign bodies, selection of biofilm-active, sensitive and well-penetrating antibiotics, systemic or topical antibiotic administration in high dosage and combinations, and administration of anti-quorum sensing or biofilm dispersal agents.
Anti-Bacterial Agents ; therapeutic use ; Bacterial Infections ; drug therapy ; microbiology ; Biofilms ; Drug Resistance, Bacterial ; Humans

Bladder cancer remains a commonly diagnosed malignancy worldwide, bringing huge economic burden and high morbidity for patients. Assessment of prognostic significance of lymphovascular invasion (LVI) is a critical issue in the surgical management of bladder cancer after transurethral resection or radical cystectomy. A systematic search of PubMed, Embase and Cochrane Library was performed up to Oct 10, 2014 to identify eligible studies. Outcomes of interest were collected from studies comparing overall survival (OS), cancer specific survival (CSS) and recurrence free survival (RFS) in patients with the LVI. Results of studies were pooled, and combined hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) for survival were used as the effect size estimation. Funnel plots were done to show the publication bias, while the forest plots and subgroup analyses were used to limit the heterogeneity. A total of 20 studies (10 663 patients) met the eligibility criteria and were included for this meta-analysis. Our pooled results showed that there were significant differences in OS (pooled HR, 1.71; 95%CI, 1.52-1.92; P<0.00001), CSS (pooled HR, 2.25; 95% CI, 1.80-2.81; P<0.00001) and RFS (pooled HR, 1.91; 95% CI, 1.57-2.32; P<0.00001) between the patients with LVI and the patients without LVI. There were significant heterogeneities observed in the studies concerning the relationship between LVI and CSS, RFS. There was no clear evidence of publication bias. When tumor stage was beyond T3, LVI lost its predictive value for CSS and RFS. For the patients who had negative lymph nodes, LVI was still an adverse predictor. Our pooled results demonstrate that LVI indicates poor prognosis of patients with bladder cancer after surgical procedures, and it can be of particular importance in clinical practice. However, these results need to be further confirmed by more adequately designed prospective studies.
Carcinoma, Squamous Cell ; diagnosis ; mortality ; pathology ; surgery ; Cystectomy ; mortality ; Female ; Humans ; Lymph Nodes ; Lymphatic Metastasis ; Male ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Survival Analysis ; Urinary Bladder Neoplasms ; diagnosis ; mortality ; pathology ; surgery ; Urothelium ; pathology ; surgery

OBJECTIVETo study the effect of Dangua Recipe (DGR) on glycolipid metabolism, vascular cell adhesion molecule-1 (VCAM-1) and its mRNA expression level of transgenic Apo E(-/-) mouse with spontaneous atherosclerosis, thus revealing its partial mechanism for curing diabetes mellitus (DM) with angiopathy.

METHODSDiabetic model was prepared by peritoneally injecting streptozotocin (STZ) to Apo E(-/-) mouse. Totally 32 modeled mice were stratified by body weight, and then divided into 4 groups referring to blood glucose levels from low to high by random digit table, i.e., the model group (MOD, fed with sterile water, at the daily dose of 15 mL/kg), the DGR group (fed with DGR at the daily dose of 15 mL/kg), the combination group (COM, fed with DGR at the daily dose of 15 mL/kg and pioglitazone at the daily dose of 4.3 mg/kg), and the pioglitazone group (PIO, at the daily dose of 4.3 mg/kg), 8 in each group. Another 8 normal glucose C57 mouse of the same age and strain were recruited as the control group. All interventions lasted for 12 weeks by gastrogavage. The fasting blood glucose (FBG), body weight, food intake, water intake, skin temperature, the length of tail, and the degree of fatty liver were monitored. The hemoglobin A1c (HbA1c), total cholesterol (TC), and LDL-C were determined. Endothelin-1 (ET-1) was determined by radioimmunoassay. Nitrogen monoxidum (NO) was determined by nitrate reductase. The kidney tissue VCAM-1 level was analyzed with ELISA. The expression of VCAM-1 mRNA in the kidney tissue was detected with real time quantitative PCR.

RESULTSCompared with the control group, the body weight and food intake decreased, water intake increased in all the other model groups (P < 0.05). Besides, the curve of blood glucose was higher in all the other model groups than in the control group (P < 0.01). Compared with the model group, the body weight increased; levels of HbAlc, TC, LDL-C, ET-1, and VCAM-1 were significantly lower; and skin temperature was higher in the DGR group (P < 0.05, P < 0.01). Compared with the PIO group, body weight, the increment of body weight, FBG, TC, and LDL-C were lower (P < 0.05, P < 0.01); food intake and water intake increased more and the tail length was longer in the DRG group (P < 0.01). There was no statistical difference in the level of NO among groups. The degree of fatty liver in the model group was significantly severer than that in the control group (P < 0.05). It was obviously alleviated in the DGR group (P < 0.05) when compared with the model group and the PIO group (P < 0.05, P < 0.01). But it was severer in the PIO group than in the model group (P < 0.01). The degree of fatty liver in the combination group ranged between that of the DGR group and the PIO group (P < 0.05). The level of VCAM-1 mRNA expression was significantly lower in the DGR group than in the model group, the PIO group, and the combination group (P < 0.05).

CONCLUSIONSDGR had effect in lowering blood glucose and blood lipids, and fighting against fatty liver of transgenic Apo E(-/-) mouse with spontaneous atherosclerosis. DGR played an effective role in preventing and treating DM with angiopathy by comprehensively regulating glycolipid metabolism and promoting the vascular function.

Animals ; Apolipoproteins E ; genetics ; Blood Glucose ; metabolism ; Diabetes Mellitus, Experimental ; blood ; drug therapy ; Diabetic Angiopathies ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Lipids ; blood ; Male ; Mice ; Mice, Knockout ; RNA, Messenger ; genetics ; Random Allocation ; Thiazolidinediones ; pharmacology ; Vascular Cell Adhesion Molecule-1 ; genetics ; metabolism

Objective To explore the treatment methods and surgical techniques of the third ventricle tumor combined with hydrocephalus under neuroendoscope. Methods The clinical data and imaging findings of 4 patients with third ventricle tumor combined with hydrocephalus, treated with surgery under neuroendoscopy, were retrospectively analyzed; and related literatures were reviewed to conclude the surgical experiences and skills. Results Three of the 4 patients were performed surgery only by neuroendoscopy, and 1 by neuroendoscopic auxiliary microscope for the tumor complete resection. The clinical symptoms improved obviously after the surgery, and no significant complications and no dead case were noted.We followed up the 4 patients for 3-18 months; MRI showed that the tumor did not relapse and the hydrocephalus got improvement. Conclusion Endoscopic navigation can help to directly reach the locations of third ventricle tumor and decrease the unnecessary damage, which enjoys its advantages in tumor resection,relieving obstructive hydrocephalus and rebuilding the cerebrospinal fluid circulation, indicating that surgery under neuroendoscope is a safe, effective and minimally invasive method.