Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

In the era of evidence-based medicine, it is necessary to explore the unique advantages of traditional Chinese medicine (TCM) based on standardized technical methods and operating procedures in order to achieve the modernization and internationalization of TCM and benefit all humanity. The proposal of a three-pronged evidence system combining TCM theory, human experience and experimental evidence marks an important progress in the thinking method of the TCM evaluation system. The multi-evidence body integrated through appropriate methods provides a strong support for the clinical guideline recommendations and evidence-based health decision-making in TCM. Based on the current methodological progress of international evidence synthesis and grading, this paper proposes a novel approach for integrating multi-evidence in TCM: the MERGE framework. The aim is to establish a solid foundation for the development of this methodology and provide guidance for the advancement of evidence-based medicine framework in TCM.

The development of clinical practice guidelines involves a series of evidence-based decision-making processes, of which the formation of recommendations is particularly challenging. It demands decision-makers to have a thorough and precise understanding of the evidence, weigh the potential benefits and risks of interventions, and make valuable judgments and clinical choices. Compared to traditional approaches of presenting evidence information, the use of visualization tools can facilitate the communication and analysis of evidence, simplify information interpretation, and improve the efficiency of decision-making. Based on previousstudies, this paper proposes a visualization tool, vitruvian plot, for summarizing evidence and provides illustrative examples to demonstrate its usage and effects, with the aim of offering valuable guidance for researchers.

Objective: To investigate the expression and molecular mechanism of dickkopf 1 ( DKK1 ) in tongue squamous cell carcinoma (TSCC) by bioinformatics method and molecular biology experiments． Methods: The patients information wasdownload from TCGA-TSCC database，the differentially expressed genes between the cancer and normal tissues were screened by NetworkAnalysed site，the key genes and clinical prognosis were identified through Kaplan-Meier analysis and Lasson regression，the functions and pathways of differentially expressed genes were gained by GO and KEGG database，the expression of DKK1 mRNA and protein in TSCC as well as its relationship with clinicopathological features were analyzed by UALCAN database and immunohistochemistry．Western blot assay was conducted to detect the protein expression of DKK1 in TSCC cells，and siRNA was used to konck down the expression of DKK1 protein in Cal27 cells. Results : The three key genes DKK1，CYP19A1 and IRX4， which were highly expressed in tongue squamous cell carcinoma and the survival rate of TSCC patients with high expression group was poor，were screened through NetworkAnalysed ，Kaplan-Meier analysis and Lasson regression method．UALCAN database showed that the mRNA level of DKK1 in TSCC tissues was higher than that in normal tissues，and its high expression was significantly correlated with clinical stage，histological grade and lymph node metastasis of TSCC patients．The immunohistochemistry assay suggested that the positive rate of DKK1 protein in clinical stage Ⅲ + Ⅳ TSCC tissues was significantly higher than that in stage Ⅰ + Ⅱ TSCC tissues．In addition， the expression level of DKK1 protein in TSCC tissues was significantly higher than that in adjacent tissues．Western blot assay also showed that the protein expression of DKK1 in TSCC cell Cal27 was much higher than normal oral epithelial cell HOEC．When knock down the protein expression of DKK1 in Cal27，the expression of β-catenin、p- p65 和 p65 werealso reduced． Conclusion DKK1 is highly expressed in tongue squamous cell carcinoma tissues and cells and plays an important role．It may be a new target for early diagnosis and drug treatment of TSCC.

Objective:To systematically compare the prognosis in non-compressible torso hemorrhage（NCTH）treated by resuscitative endovascular balloon occlusion of the aorta（REBOA）and resuscitation thoracotomy（RT）.Methods:Data were searched form MEDLINE, EMBASE, PubMed, WanFang, CNKI and VIP databases to collect studies on the prognosis of patients with NCTH undergone REBOA and RT from inception to December 2020. Two reviewers independently screened studies according to the inclusion and exclusion criteria, extracted data and evaluated the quality of the included studies. The Meta-analysis was performed using Revman 5.3. The patients were divided into REBOA group and RT group according to the different surgical treatment methods on admission, and the prognosis of each group was evaluated. The difference of mortality rate, reoperation rate of laparotomy after operation, reoperation rate of embolization after operation and mortality rate in different operating room area were compared between the two groups. Publication bias was assessed using the Egger test.Results:A total of 2 prospective studies and 4 retrospective studies involving 2, 588 subjects were included. There were 1, 591 patients in REBOA group and 997 patients in RT group. Significant differences were observed in the mortality rate（ I2=68%, OR=0.33, 95% CI 0.26-0.42, P<0.01）, reoperation rate of laparotomy after operation（ I2=76%, OR=1.41, 95% CI 1.11-1.77, P<0.01）and reoperation rate of embolization after operation（ I2=84%, OR=0.76, 95% CI 0.59-0.99, P<0.05）between REBOA group and RT group. Subgroup analysis showed that the mortality rate in the ICU were not statistically different between the two groups（ I2=83%, OR=0.69, 95% CI 0.45-1.05, P>0.05）, but the mortality rate in the emergency room was lower in REBOA group than that in RT group（ I2=94%, OR=0.52, 95% CI 0.38-0.70, P<0.01）. Egger test showed that publication bias had little effect on the results. Conclusions:For patients with NCTH, REBOA can reduce the mortality rate and reoperation rate of embolization after operation, but increase the reoperation rate of laparotomy after operation when compared with RT. In addition, the emergency room may be a more suitable operationg room area for REBOA.

Objective The expression of TNF-α was detected in sera of rabbits treated by ulinastatin with acute lung injury in duced by underwater explosion.Methods Rabbits were randomly divided into two groups such as the injured group and ulinastatin therapy group.Established underwater explosion device was used to cause acute lung injury in rabbits.TNF-α in sera of the rabbits were measured by ELISA at 4,12 and 24 hours after the explosion.The SPSS17.0 software was used to analyze the data and P＜0.05 was considered to be significant.Results There was no significant difference between the concentrations of TNF-α in the sera of rabbits in the injure group (538.20±201.43 ng/L) and that of in the ulinastatin group (386.90± 109.22 ng/L,t=2.088,P=0.051) at 4 hours after burst.However,there was evidently decreased in the level of TNF-α in the ulinastatin group (400.60 ± 78.98 ng/L) compared with the injury group (573.80 ± 178.24 ng/L,t =2.809,P =0.012) at 12 hours after burst.Moreover and TNF-α in the ulinastatin group (356.10 ± 130.99 ng/L) was also decreased compared to the injure group (552.30± 169.64 ng/L,t=2.895,P=0.010) at 24 hours after burst.Conclusion The TNF-α expression in sera of the rabbits in ulinastatin group were dramatically decreased than thai of in injury group at 12 hours after burst,which may be benefit to rabbits with acute lung injury induced by underwater explosion.

The copy numbers of exogenous gene in transgenic animals is always regarded as an important information of transgenic animals.Thus,simple and sensitive methods are required for the detection of the copy numbers of exogenous gene.Three kinds of transgenic Shanbei white cashmere goats,containing Tβ4-GFP,FGF5s-GFP and VEGF164-GFP,has been obtained by using PiggyBac(PB) transposon system.Fluorescence quantitative PCR was carried out to detect the copy numbers of copGFP.Using Gluc as reference gene,the double standard curves of exogenous gene and reference gene were mapped and the genomic DNA of transgenic goats were analysized by real-time fluorescence quantitative PCR.Moreover,the copGFP/Gluc ratio in the samples was calculated as the copy numbers of copGFP.In addition,Tβ4-GFP transgenic cashmere goats were selected to detect the integration sites by using the genomic walking kit.The results showed that the standard curve equation of copGFP was y=-3.230 6x+39.216 (R2 =0.998 8) and the standard curve equation of Gluc was y=-3.564 8x+38.440 (R2 =0.996 0).The copy numbers of exogenous gene in the transgenic cashmere goats were obtained and the numbers of integration sites in the selected Tβ4-GFP transgenic goats were consistent with the copy numbers of copGFP.As a conclusion,the high throughput,fast and sensitive real-time fluorescence quantitative PCR is an efficient and convenient method for the copy number of exogenous gene in transgenic cashmere goats.

Acute myeloid leukemia (AML),the most common disease in acute leukemia,is a highly heterogeneous invasive hematological disease.The t(8;21)(q22;q22) translocation is the most common chromosomal translocation in AML,generating AML1-ETO fusion gene and encoding AML1-ETO fusion protein.This article summarizes the two-hit hypothesis in AML occurrence,the pathogenesis of t(8;21)AML,all features involved in t(8;21)AML,and the function of the components in AML1-ETO fusion protein,providing important basic information for the treatment and prognosis of t(8;21)AML.Meanwhile,this article also summarizes the progress of next generation sequencing technique in leukemia,providing a new technique for the accurate therapy of (8;21)AML.

Objective To better understand the clinical characteristics of Familial Idiopathic Basal Ganglia Calcifi?cation (FIBGC), including at the perspective of hereditary pattern, clinical test results, onset age, clinical heterogeneity and the volume of basal ganglia calcification (VBGC). Method 8 Eight FIBGC families were collected and draw family pedigrees were draw. Analysis of was conducted on the patient's clinical test results, head CT and MRI changes, onset ag?es, relationship of clinical manifestations with VBGC. Results No significant difference was found in serum calcium, alu?minum, arsenic, cobalt, magnesium, phosphorus, iron, parathyroid hormone and calcitonin concentration between the fam?ily members of patients and healthy controls (P>0.05). Family members from 8 FIBGC families including the two with consanguineous marriage manifested autosomal dominant heredity. The severity of , symptomatic s was correlated with VBGCpatients showed the same clinical manifestations in the dyskinesia family. The psychiatric symptoms was not asso? ciated with VBGC whereas patients with dyskinesia had a large VBGC. There was a significant difference in onset age be?tween patients with psychiatric symptoms and those with dyskinesia. P.atients with dyskinesia suffer larger VBGC, and is characterized by Patients with dyskinesia had relatively later onset age (43.95 ± 2.47 y) whereas those with. psychiatric symptoms hadsymptomatic patients with early onset age (31.32±10.16y). The comparison of the onset age (43.954±2.473 vs. 31.319±10.156 y, t=4.438, P=0.001) and VBGC (1.748±0.622 vs. 0.392±0.276 cm3, t=2.518, P=0.028) with symptom?atic patients between dyskinesia and psychogenic families was significant. Conclusions Eight FIBGC families manifested autosomal dominant heredity. Patients with dyskinesia suffer have a larger VBGC and are associated with a, and is char?acterized by relatively later onset age. In contrast, patients with psychiatric symptomspsychogeny is not related withhave a the small VBGC and showedand their age of onset is young. earlier onset age.

Objective To investigate activated nano carbon in prophylactic central lymph node dissection of T1 papillary thyroid non-microcarcinoma.Methods Patients with T1 papillary thyroid non-microcarcinoma in Thyroid Surgery Department of Sun Yat-sen Memorial Hospital of Sun Yat-sen University undergoing surgery from Jan.2012 to Jun.2013 were divided into 2 groups:odd numbers were the experimental group,and even numbers were the control group.Activated nano carbon was injected in the affected side of the thyroid in the experimental group.The lymph node metastasis,parathyroid function,and the rate of recurrent laryngeal nerve (RLN) injury were compared between the 2 groups.Results The total number of resected lymph nodes in the experimental group and the control group were 327 and 238 respectively.The positive lymph nodes in the experimental group and the control group were 120 (36.7％)and 56 (23.5 ％)respectively.The difference had statistical significance (P =0.000 85).The number of patients with lymphatic metastasis in the experimental group and the control group was 42 (56％) and 30 (40％) respectively.The difference had statistical significance (P =0.049 9).The average number of positive lymph node for patients in the experimental group and the control group was (2.86 ± 0.13) and(1.87 ± 0.09) respectively.The difference had statistical significance(P =0.009).The rate of transient hypoparathyroidism in the experimental group and the control group was 34.7％ and 60％ respectively.The difference had statistical significance (P =0.002).The incidence of hoarseness caused by RLN injury was 2.7％ and 4％ respectively in the experimental group and the control group.The difference had no statistical significance(P =1.000).Conclusions Activated nano carbon plays an important role in prophylactic central lymph node dissection of T1 papillary thyroid non-microcarcinoma phase.It not only contributes to lymph node dissection,but also protects parathyroid.However,it can't reduce the incidence of RLN injury.