Effect of Bismuth Subgallate/Borneol Combined with Autologous Platelet-Rich Gel in the Treatment of Patients with Diabetic Foot Ulcers

Objective: To explore the effect of Bismuth Subgallate/Borneol (SuileTM BSB) healing dressing combined with autologous platelet-rich gel (APG) in the treatment of diabetic foot ulcer (DFU). Methods: A total of 120 patients with DFU hospitalized in the Changsha Central Hospital from August 2020 to September 2021 were selected and randomly divided into an experimental group (BSB + APG, n = 60) and a control group (BSB, n = 60) according to random number table method. The total therapeutic effect, healing time, hospital stay, level indexes of various inflammatory factors before and after treatment and ulcer area were observed in the two groups. Results: The total effect of the control group was worse than that of the experimental group, and the data between the two groups were significant (P 0.05);after treatment, the levels of inflammatory factors including WBC, CRP, IL-6 and TNF-α in the control group were higher than those in the experimental group, and there was significant difference between the two groups (P 0.05);after 14 days of treatment, the ulcer area in the control group was larger than that in the experimental group, and the data between the two groups were significant (P Conclusion: BSB combined with APG can achieve better therapeutic effect, reduce the inflammatory reaction of patients, and promote wound healing in the treatment of patients with diabetic foot ulcer.

Comparison of efficacy of conbercept,aflibercept,and ranibizumab ophthalmic injection in the treatment of macular edema caused by retinal vein occlusion:a Meta-analysis

AIM:To evaluate and compare the anatomical and functional outcomes and negative effects of the three anti-vascular endothelial growth factor(VEGF)drugs in the treatment of macular edema(ME)due to retinal vein occlusion(RVO)based on the evidence pooled from current clinical trials and observational studies.METHODS:A systematic literature search was conducted on nine online databases from inception until April 30,2022.The main endpoints were best corrected visual acuity(BCVA),central macular thickness(CMT),and adverse events(AEs).Cumulative Meta-analysis was conducted to synthesize the outcomes of the drugs.The retrieved data were analyzed using Stata software(version 12.0).RESULTS:A total of 20 studies comprising 1674 eyes met the inclusion criteria to the Meta-analysis.It was observed that conbercept and aflibercept had better visual acuity effects compared with ranibizumab at 1mo[weight mean difference(WMD)=-0.03,P=0.001;WMD=-0.05,P=0.019],but the effects were not different from that of ranibizumab at 6mo.Moreover,there was not statistically significant dif ference in the propor tion of patients gaining≥15 letters at 12-24mo between aflibercept and ranibizumab[odds ratio(OR)=1.16,P=0.427].Conbercept had higher mean CMT change effects at 1mo(WMD=-14.43,P=0.014)and 6mo(WMD=-35.63,P≤0.001)compared with ranibizumab.Meanwhile,the mean CMT change effects at 1mo(WMD=-10.14,P=0.170),6mo(WMD=-26.98,P=0.140)and 12-24mo(WMD=-12.34,P=0.071)were comparable among the groups.Similarly,AEs were not significantly different among the treatments(OR=0.75,P=0.305;OR=1.04,P=0.89).The stability of effect size of mean BCVA and CMT improved with the increase in sample size.Aflibercept and conbercept required fewer injections compared with ranibizumab.CONCLUSION:This is the first study to evaluate the efficacy and AEs of intravitreal administration of conbercept,ranibizumab,and aflibercept in the treatment of RVOME.Intravitreal aflibercept or conbercept results in better mean change in vision and CMT reduction compared with ranibizumab.Conbercept can be considered to be a promising and innovative drug with good anti-VEGF effects.

Global trend and future landscape of intestinal microcirculation research from 2000 to 2021:A scientometric study

BACKGROUND The intestinal microcirculation functions in food absorption and metabolic substance exchanges.Accumulating evidence indicates that intestinal microcirculatory dysfunction is a significant source of multiple gastrointestinal diseases.To date,there has not been a scientometric analysis of intestinal microcirculatory research.AIM To investigate the current status,development trends,and frontiers of intestinal microcirculatory research based on bibliometric analysis.METHODS VOSviewer and CiteSpace 6.1.R2 were used to identify the overall characteristics and knowledge map of intestinal microcirculatory research based on the core literature published from 2000 to 2021 in the Web of Science database.The characteristics of each article,country of origin,institution,journal,cocitations,and other information were analyzed and visualized.RESULTS There were 1364 publications enrolled in the bibliometric analysis,exhibiting an upward trend from 2000 to 2021 with increased participation worldwide.The United States and Dalhousie University took the lead among countries and institutions,respectively.Shock was the most prolific journal,and Nature Reviews Microbiology Clinical had the most citations.The topical hotspots and frontiers in intestinal microcirculatory research were centered on the pathological processes of functional impairment of intestinal microvessels,diverse intestinal illnesses,and clinical treatment.CONCLUSION Our study highlights insights into trends of the published research on the intestinal microcirculation and offers serviceable guidance to researchers by summarizing the prolific areas in intestinal disease research to date.

Exogenous bone morphogenetic protein-7 reduces hepatic fibrosis inSchistosoma japonicum-infected micevia transforming growth factor-β/Smad signaling

AIM: To investigate the antifibrotic effects of bone morphogenetic protein-7 (BMP-7) on Schistosoma japonicum (S. japonicum )-induced hepatic fibrosis in BALB/C mice. METHODS: Sixty BALB/C mice were randomly divided into three groups, including a control group (group A, n = 20), model group (group B, n = 20) and BMP-7 treated group (group C, n = 20). The mice in group B and group C were abdominally infected with S. japonicum cercariae to induce a schistosomal hepatic fibrosis model. The mice in group C were administered human recombinant BMP-7. Liver samples were extracted from mice sacrificed at 9 and 15 wk after modeling. Hepatic histopathological changes were assessed using Masson's staining. Transforming growth factor-beta 1 (TGF-β1), alpha-smooth muscle actin (α-SMA), phosphorylated Smad2/3 (pSmad2/3) and Smad7 protein levels and localization were measured by Western blotting and immunohistochemistry, respectively, and their mRNA expressions were detected by reverse transcriptionpolymerase chain reaction (RT-PCR). RESULTS: The schistosomal hepatic fibrosis mouse model was successfully established, as the livers of mice in group B and group C showed varying degrees of typical schistosomal hepatopathologic changes such as egg granuloma and collagen deposition. The degree of collagen deposition in group C was higher than that in group A (week 9: 22.95±6.66vs 2.02±0.76; week 15: 12.84±4.36 vs 1.74±0.80; P<0.05), but significantly lower than that in group B (week 9: 22.95±6.66 vs 34.43±6.96; week 15: 12.84±4.36 vs 18.90±5.07;P<0.05) at both time points. According to immunohistochemistry data, the expressions of α-SMA, TGF-β1 and pSmad2/3 protein in group C were higher than those in group A (α-SMA: week 9: 21.24±5.73 vs 0.33±0.20; week 15: 12.42±4.88 vs 0.34±0.27; TGF-β1: week 9: 37.00±13.74 vs 3.73±2.14; week 15: 16.71±9.80 vs 3.08±2.35; pSmad2/3: week 9: 12.92±4.81 vs 0.83±0.48; week 15: 7.87±4.09 vs 0.90±0.45; P<0.05), but significantly lower than those in group B (α-SMA: week 9: 21.24±5.73 vs 34.39±5.74; week 15: 12.42±4.88 vs 25.90±7.01; TGF-β1: week 9: 37.00±13.74 vs 55.66±14.88; week 15: 16.71±9.80 vs 37.10±12.51; pSmad2/3: week 9: 12.92±4.81 vs 19.41±6.87; week 15: 7.87±4.09vs 13.00±4.98;P<0.05) at both time points; the expression of Smad7 protein in group B was higher than that in group A and group C at week 9 (8.46±3.95 vs 1.00±0.40 and 8.46±3.95 vs 0.77±0.42; P<0.05), while there were no differences in Smad7 expression between the three groups at week 15 (1.09±0.38 vs 0.97±0.42 vs 0.89±0.39; P>0.05). Although minor discrepancies were observed, the results of RT-PCR and Western blotting were mainly consistentwith the immunohistochemical results. CONCLUSION: Exogenous BMP-7 significantly decreased the degree of hepatic fibrosis in both the acute and chronic stages of hepato-schistosomiasis, and the regulatory mechanism may involve the TGF-β/Smad signaling pathway.

Effect of ephrin-B2 on the expressions of angiopoietin-1 and-2 after focal cerebral ischemia/reperfusion

Ephrin-B2 has been shown to participate in angiogenesis, but the underlying mechanisms involved remain unclear. In this study, a rat model of local cerebral ischemia was prepared by focal middle cerebral artery occlusion, followed by 24-hour reperfusion. Then, ephrin-B2 protein was administered intracerebroventricularly for 3 consecutive days via a micro-osmotic pump. Western blot assay and quantitative real-time reverse transcription PCR demonstrated the expression levels of angiopoietin-1 （Ang-1） mRNA and protein in the penumbra cortex of the ephrin-B2 treated group were decreased at day 4 after reperfusion, and increased at day 28, while the expression levels of angiopoietin-2 （Ang-2） were highly up-regulated at all time points tested. Double immunofluorescent staining indicated that Ang-1 and Ang-2 were both expressed in vascular endothelial cells positive for CD31. These findings indicate that ephrin-B2 influences the expressions of Ang-1 and Ang-2 during angiogenesis following transient focal cerebral ischemia.

Osteopontin expression is associated with hepatopathologic changes in Schistosoma japonicum infected mice

AIM:To investigate osteopontin expression and its association with hepatopathologic changes in BALB/C mice infected with Schistosoma japonicum.METHODS:The schistosomal hepatopathologic mouse model was established by abdominal infection with schistosomal cercaria.Liver samples were obtained from mice sacrif iced at 6,8,10,14,and 18 wk after in-fection.Liver histopathological changes were observed with hematoxylin-eosin and Masson trichrome staining.The expression of osteopontin was determined with im-munohistochemistry,reverse transcription-polymerase chain reaction,and Western blotting.The expressionof α-smooth muscle actin(α-SMA)and transforming growth factor-β1(TGF-β1)were determined by im-munohistochemistry.Correlations of osteopontin ex-pression with other variables(α-SMA,TGF-β1,hepato-pathologic features including granuloma formation and degree of liver f ibrosis)were analyzed.RESULTS:Typical schistosomal hepatopathologic changes were induced in the animals.Dynamic changes in the expression of osteopontin were observed at week 6.The expression increased,peaked at week 10(P<0.01),and then gradually decreased.Positive correla-tions between osteopontin expression and α-SMA(r=0.720,P<0.01),TGF-β1(r=0.905,P <0.01),granu-loma formation(r=0.875,P<0.01),and degree of liver f ibrosis(r=0.858,P<0.01)were also observed.CONCLUSION:Osteopontin may play an important role in schistosomal hepatopathology and may promote granuloma formation and liver fi brosis through an un-explored mechanism.

Gut-lung crosstalk in pulmonary involvement with inflammatory bowel diseases

Pulmonary abnormalities,dysfunction or hyper-reactivity occurs in association with inflammatory bowel disease(IBD) more frequently than previously recognized.Emerging evidence suggests that subtle inflammation exists in the airways among IBD patients even in the absence of any bronchopulmonary symptoms,and with normal pulmonary functions. The pulmonary impairment is more pronounced in IBD patients with active disease than in those in remission. A growing number of case reports show that the IBD patients develop rapidly progressive respiratory symptoms after colectomy,with failure to isolate bacterial pathogens on repeated sputum culture,and often request oral corticosteroid therapy. All the above evidence indicates that the inflammatory changes in both the intestine and lung during IBD. Clinical or subclinical pulmonary inflammation accompanies the main inflammation of the bowel.Although there are clinical and epidemiological reports of chronic inflammation of the pulmonary and intestinal mucosa in IBD,the detailed mechanisms of pulmonaryintestinal crosstalk remain unknown. The lung has no anatomical connection with the main inflammatory site of the bowel. Why does the inflammatory process shift from the gastrointestinal tract to the airways? The clinical and subclinical pulmonary abnormalities,dysfunction,or hyper-reactivity among IBD patients need further evaluation. Here,we give an overview of the concordance between chronic inflammatory reactions in the airways and the gastrointestinal tract. A better understanding of the possible mechanism of the crosstalk among the distant organs will be beneficial in identifying therapeutic strategies for mucosal inflammatory diseases such as IBD and allergy.

Pembrolizumab-Induced Steven-Johnson Syndrome in an NSCLC Patient: A Case Report

Background: Immune checkpoints inhibitors (ICIs) are widely used in various therapy of tumors. With the increasing usage of them, immune-related adverse events (irAEs) have been known and become common events, especially in the dermatologic system. However, the rare and severe immune-related cutaneous adverse events (irCAEs) still lack enough knowledge. Case presentation: We described a rare case of Steven-Johnson syndrome (SJS) induced by pembrolizumab in an advanced squamous non-small cell lung cancer (NSCLC) patient. SJS is a rare irCAE that could happen at any time after immunotherapy while this case happened from the 3rd day. The patient had influence-like symptoms and several mucous lesions including oral, eye, and skin. With a gradually severer condition, a stoss therapy of intravenous immunoglobulin (IVIG) had a mild effect. It was a long process and failed to respond to usual dermatologic treatment. Conclusion: We share this case in order to enhance clinicians’ ability to early recognition and diagnosis in severe irCAEs. Early recognition and appropriate management are important to evade the termination of immunotherapy. Such severe irCAE should be paid more attention to in clinical medicine when using ICIs.

The effect and mechanism of Tip60 regulating DNA on embryo development

Objective: To study the effect and mechanism of Tip60 regulating DNA on mouse embryo development, and to provide theoretical basis for the study of embryo development. Methods: mice embryos were randomly divided into two groups: control group and experimental group. The embryos of experimental group were given Tip60 inhibitor, the mice of control group were given the same dose of normal saline. The level of Tip60 in the two groups of mice embryos, the effect of Tip60 on p53-p21 pathway, the expression of DNA repair factor 53BP1 protein, the content of active oxygen, the effect of autophagy and apoptosis, and the development of embryos were analyzed. Results: the level of Tip60 in the experimental group was significantly lower than that in the control group;the p53-p21 pathway in the experimental group was activated, the DNA damage of the experimental group was greater, the expression of DNA repair factor was lower, the content of ROS in the experimental group was significantly higher than that in the control group;the autophagy and apoptosis of the experimental group were enhanced;the capsule of the control group was enhanced. The embryogenesis rate of the experimental group was (65.13 ± 4.85)%, and that of the experimental group was (29.36 ± 1.75)%, which was significantly lower than that of the control group. Conclusion: Tip60 can regulate DNA damage and repair by mediating p53-p21 pathway in early mouse embryo development. Inhibition of Tip60 can increase the active oxygen, induce autophagy and over expression of apoptosis in mouse embryo cells, and inhibit the development of embryo to a certain extent. It has important guiding significance to measure the level of Tip60 during embryo culture.

Clear Cell Myo-Melanomas of Ligamentum Teres Hepatis: A Case Report and Literature Review

Introduction: Clear Cell Myomelanocytic Tumor (CCMMT) of ligamentum teres hepatis is a pathological classification of Perivascular Epithelioid Cell tumor (PEComa), which is rare clinically and easy to misdiagnose. Objective: To report a case of a rare type of PEComa located in the ligamentum teres hepatis. Case Report: A 22-year-old Asian female was diagnosed with abdominal mass during physical examination in September 2018, and was admitted to the general surgery department of our hospital that month. She was diagnosed with abdominal mass, the nature of which remains to be determined is: teratoma, pheochromocytoma or ganglioma. At the time of admission, the patient had no symptoms or signs, and no other medical history. The patient was diagnosed with an abdominal mass by abdominal plain scan and enhanced CT, whose nature was to be determined: pheochromocytoma, paragangliomas or other mesenchymal tumors, or giant lymph node hyperplasia. The patient underwent abdominal mass resection and appendectomy without incident, without any complications at discharge, and there was no significant difference in follow-up. Conclusions: The clinical data, imaging features and pathological features of one patient diagnosed with CCMMT in our hospital were retrospectively analyzed, and the literature was reviewed in combination with the research progress of CCMMT, in order to improve the understanding and diagnostic accuracy of this disease.

Histiocytic Necrotizing Lymphadenitis: A Clinical Study of 6 Children and Review

Objective: As a rare cause of fever and lymphadenopathy (especially in the neck) in children, the purpose of this study is to explore the clinical characteristics of histiocytic necrotizing lymphadenitis (HNL) in children and improve the diagnosis and treatment of this disease. Methods: We retrospectively collected the data of 6 pediatric patients with HNL diagnosed by lymph node biopsy from 2012 to 2021 in department of pediatric, the affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, including the clinical characteristics, laboratory examinations, imaging findings and histopathological examinations, treatment and follow-up of the patients and reviewed relevant literature. Results: All the patients were Han girls, with no kinship with each other, and four cases were from rural areas. The age of onset was from 7 to 14 years old, with durations ranged from 1 week to 3 months. All children had cervical lymphadenopathy with tenderness, five cases of fever, two cases of cough, one case of weight loss, four cases of leukopenia, one case of liver impairment, one case of combined bacterial infection of leukocytosis. All children underwent lymph node biopsy and were diagnosed with HNL, four children were treated with anti-infection before diagnosis, two children were treated with steroid therapy after diagnosis, and 1 case of weakened immune function was used immunoglobulin for modulating immunity. All children improved and discharged, and no recurrence was observed until October 2021. Conclusion: In our study, the children with swollen lymph nodes in the neck were accompanied by tenderness and fever as the main clinical manifestations, without specificity. Histopathology and immunohistochemical examination by removing the affected lymph nodes could confirm HNL. Most children had a good prognosis and long-term follow-up were required.

Factors associated with in-hospital mortality in sepsis patients admitted to the emergency department:A retrospective study

Objective Most patients with sepsis were diagnosed in the emergency department when admitted to the hospital. This study aimed to explore independent factors for hospital mortality in sepsis patients in the emergency department.Methods It was a retrospective study. All patients with sepsis admitted to the emergency department of Changsha Central Hospital between 1 July 2020 and 1 July 2021 were included. Variables that showed significant differences between the survivor group and the non-survivor group were caculated in multivariate logistic regression analysis. Independent factors associated with in-hospital mortality in sepsis were identified.Results A total of 194 patients were included in this study. In-hospital mortality was 17.01%(n=33). Two independent risk factors including albumin(ALB) and urea nitrogen were identified by multivariate logistic regression analysis. The optimal cut-off values of ALB and urea nitrogen were 26.5g/L and 8.03mmol/L. While combined ALB and urea nitrogen, the area under the ROC curve(AUC) was 0.790, which was superior to the SOFA, qSOFA, and APACHEⅡscores.Conclusions Independent factors including ALB and urea nitrogen for in-hospital mortality in sepsis in the emergency department were identified. It could help physicians identify those patients with a higher risk of a poor prognosis early and easily, so intervention and management could be performed quickly.

The relationship between uric acid and blood pressure in patients with diabetes:results from NHANES database

Objective This study aimed to explore the association between uric acid(UA)and blood pressure(BP)in patients with diabetes receiving anti-diabetic therapy.Methods A cross-sectional study with 2878 individuals from the National Health and Nutrition Examination Survey(NHANES)was performed.Multiple linear regression analysis was applied to explore the relationship between UA and BP in the antihypertensive and anti-diabetic group(n=1966)and the anti-diabetic group(n=912).Results Between the group with antihypertensive and anti-diabetic therapy and the group with anti-diabetic therapy alone,no significant association was found with systolic blood pressure(SBP).However,the significantly negative association was present in diastolic blood pressure(DBP),and the size of the effect was(β,-0.35(95%CI:-0.68~-0.02))and(β,-0.60(95%CI:-1.13~-0.08)),respectively.The trend test was not significant between UA and SBP in two groups,but the trend test was significant between UA and DBP in the antihypertensive and anti-diabetic group(P=0.005).Conclusion In our study,we found that the association between UA and DBP in patients with diabetes receiving anti-diabetic therapy was negative.

3-Methyladenine potentiates paclitaxel-induced apoptosis and phosphorylation of cyclin-dependent kinase 1 at thr161 in nasopharyngeal carcinoma cell

Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is typically accompanied by a poor prognosis.Exploring the synergistic potential of combining multiple chemotherapeutic agents may represent a promising avenue for optimizing treatment efficacy.Methods:This study investigated whether 3-Methyladenine(3-MA)could potentiated the effect of PTX and its potential molecular mechanism.Samples were divided into the following categories:Negative control(NC)with the solvent dimethyl sulfoxide(DMSO,0.5%v/v),PTX(400 nM),3-MA(4 mM),and PTX(400 nM)+3-MA(4 mM).The viability of NPC cells was assessed using both the cell counting kit-8(CCK-8)assay and the colony formation assay.Microscopic observation was performed to identify morphological cell changes.Flow cytometry was used to assess cell cycle status,mitochondrial membrane potential(MMP),and apoptotic cells.Western blotting was conducted to quantify the protein expression.Results:3-MA enhanced PTX-specific inhibition of NPC cell proliferation.PTX,either alone or in combination with 3-MA,caused cell cycle halt at the G2/M phase in the majority of NPC cells,and the combination treatment of PTX with 3-MA induced a higher rate of NPC cell death compared to PTX alone.Western blotting results revealed the combination of PTX with 3-MA heightened activation of cyclin-dependent kinase 1(CDK1),a key molecule in shifting cells from mitotic arrest to apoptosis,led to a reduction in Myeloid Cell Leukemia 1(MCL-1)expression and an increase in Poly(ADP-ribose)polymerase(PARP)cleavage.Conclusion:The concurrent administration of PTX with 3-MA effectively enhances PTX’s inhibitory impact on NPC and activates the apoptosis signal regulated by CDK1.

Red blood cell distribution width is associated with in-hospital mortality in sepsis with MRSA infection in MIMIC-Ⅳ

Background This study aimed to explore the associations of factors with in-hospital mortality in sepsis with MRSA infection based on the MIMIC-Ⅳdatabase.Methods All sepsis patients with MRSA infection were included.Multivariate regression analysis was applied to identify predictive factors.Models were applied to explore the relationship between the factors and in-hospital mortality after adjusting potential cofounders.Results A total of 157 patients were included including a survivor group(n=111)and a non-survivor group(n=46)were included.RDW was identified as an independent factor with in-hospital mortality.A smooth fitting curve for a positive linear relationship between RDW and in-hospital mortality was constructed.The area under the ROC curve(AUC)was 0.652 with a sensitivity of 0.565 and a specificity of 0.676.The optimal cut-off value of RDW was 16.55.Compared with SOFA and APACHEⅡscores,RDW had a better predictive performance.Conclusion RDW was associated with clinical outcomes in sepsis with MRSA infection.

Hematocrit is associated with in-hospital mortality in sepsis with streptococcus pneumoniae infection based on MIMIC-Ⅳ database

Background Streptococcus pneumoniae,as a respiratory tract common pathogen,can cause invasive disease and sepsis.This study aimed to investigate the association of factors with clinical outcomes in sepsis with streptococcus pneumoniae infection based on MIMIC-IV database.Methods The sepsis patients with streptococcus pneumoniae infection were included.Different variables between the survivor group and the non-survivor group were analyzed.Multivariable logistic regression was applied to identify the factors which were associated with clinical outcomes.Results A total of 80 sepsis patients with streptococcus pneumoniae infection were included.The in-hospital mortality was 23.75%(n=19).Significant differences were found in heart rate,white blood cell,RDW,MCV and hematocrit between the survivor group and the non-survivor group.The area under the ROC curve of hematocrit was 0.758 with a sensitivity of 73.7%and a specificity of 72.1%.The cut-off value of hematocrit was 30.8%.Conclusions Hematocrit level was identified to be negatively associated with in-hospital mortality in sepsis with streptococcus pneumoniae infection.

Graphene oxide/gallium nanoderivative as a multifunctional modulator of osteoblastogenesis and osteoclastogenesis for the synergistic therapy of implant-related bone infection

Currently,implant-associated bacterial infections account for most hospital-acquired infections in patients suffering from bone fractures or defects.Poor osseointegration and aggravated osteolysis remain great challenges for the success of implants in infectious scenarios.Consequently,developing an effective surface modification strategy for implants is urgently needed.Here,a novel nanoplatform(GO/Ga)consisting of graphene oxide(GO)and gallium nanoparticles(GaNPs)was reported,followed by investigations of its in vitro antibacterial activity and potential bacterium inactivation mechanisms,cytocompatibility and regulatory actions on osteoblastogenesis and osteoclastogenesis.In addition,the possible molecular mechanisms underlying the regulatory effects of GO/Ga nanocomposites on osteoblast differentiation and osteoclast formation were clarified.Moreover,an in vivo infectious microenvironment was established in a rat model of implant-related femoral osteomyelitis to determine the therapeutic efficacy and biosafety of GO/Ga nanocomposites.Our results indicate that GO/Ga nanocomposites with excellent antibacterial potency have evident osteogenic potential and inhibitory effects on osteoclast differentiation by modulating the BMP/Smad,MAPK and NF-κB signaling pathways.The in vivo experiments revealed that the administration of GO/Ga nanocomposites significantly inhibited bone infections,reduced osteolysis,promoted osseointegration located in implant-bone interfaces,and resulted in satisfactory biocompatibility.In summary,this synergistic therapeutic system could accelerate the bone healing process in implant-associated infections and can significantly guide the future surface modification of implants used in bacteria-infected environments.

Involvement of hydrogen sulfide in the progression of renal fibrosis

Objective:Renal fibrosis is the most common manifestation of chronic kidney disease(CKD).Noting that existing treatments of renal fibrosis only slow disease progression but do not cure it,there is an urgent need to identify novel therapies.Hydrogen sulfide(H2S)is a newly discovered endogenous small gas signaling molecule exerting a wide range of biologic actions in our body.This review illustrates recent experimental findings on the mechanisms underlying the therapeutic effects of H2S against renal fibrosis and highlights its potential in future clinical application.Data sources:Literature was collected from PubMed until February 2019,using the search terms including"Hydrogen sulfide,""Chronic kidney disease"MRenal interstitial fibrosis,"Kidney disease,""Inflammation factor,""Oxidative stress,""Epithelialto-mesenchymal transition,""H2S donor,""Hypertensive kidney dysfunction,""Myofibroblasts,""Vascular remodeling,""transforming growth factor(TGF)-beta/Smads signaling,"and"Sulfate potassium channels."Study selection:Literature was mainly derived from English articles or articles that could be obtained with English abstracts.Article type was not limited.References were also identified from the bibliographies of identified articles and the authors5 files.Results:The experimental data confirmed that H2S is widely involved in various renal pathologies by suppressing inflammation and oxidative stress,inhibiting the activation of fibrosis-related cells and their cytokine expression,ameliorating vascular remodeling and high blood pressure,stimulating tubular cell regeneration,as well as reducing apoptosis,autophagy,and hypertrophy.Therefore,H2S represents an alternative or additional therapeutic approach for renal fibrosis.Conclusions:We postulate that H2S may delay the occurrence and progress of renal fibrosis,thus protecting renal function.Further experiments are required to explore the precise role of H2S in renal fibrosis and its application in clinical treatment.

Renal Fibrosis and Mitochondrial Damage

The first observations of intracellular structures that probably represented mitochondria were published in the 1840s.The mitochondrion (plural mitochondria)is a double membrane-bound organism that consists of the outer mitochondrial membrane (OMM),intermembrane space, inner mitochondrial membrane,and matrix space,[1] which is prevalent in all mammalian eukaryotic cells other than mature ervthrocytes.

The substitution V379I in PA protein attenuates the pathogenicity of influenza A(H1N1)pdm09 viruses in mice

Dear Editor,Since August 2010,the world was in the post-pandemic period and the influenza A(H1N1)pdm09(pdmH1N1)virus co-circulated with H3N2 and B virus seasonally(WHO,2010).The continuous surveillance on the pdmH1N1 virus in the post-pandemic period was recommended by WHO.In order to detect unusual events that might indicate a shift in severity disease,or emergence of a new virus,we collected a total of 312 throat swabs of laboratory-confirmed pdmHlNl patients from Hunan and Jilin provinces in