Moxibustion at ST36 activates peritoneal macrophages in CTX-induced immunosuppression in mouse model via IFN-γ

Background:To explored whether moxa cone moxibustion can reduce peritoneal inflammation by increasing the content of peritoneal macrophages and B cells via interferon-gamma.Methods:The mice were randomly divided into three groups with six mice in each group:the control group,model group,and moxibustion group,and the model was established in mice using cyclophosphamide.In the moxibustion group,the mice received moxa cone moxibustion at Zusanli(ST36)for 7 days.Analysis of Peritoneal cell were detected by flow cytometry and immunofluorescence,the protein expression level in the peritoneal fluid were measured with mouse cytokine antibody arrays and verified by enzyme linked immuno sorbent assay test,and RNA-Sequencing was used for peritoneal cell RNA analysis.Results:Our results showed that moxa cone moxibustion could reduce the loss of large peritoneal macrophages and B1 cells(P<0.05).With the cytokine array analysis and enzyme linked immuno sorbent assay test of peritoneal fluid,we found that IFN‐γwas up-regulated in moxibustion group(P<0.05).There were 169 genes were down-regulated in the model group and up-regulated in the moxibustion group while 19 genes that were up-regulated in the model group and down-regulated in the moxibustion group via RNA-sequencing.Kyoto Encyclopedia of Genes and Genomes pathway analysis of 188 intersect differentially expressed genes were found that the top 3 pathways with the highest enrichment of up-regulated genes included Hematopoietic cell lineage,Inflammatory bowel disease and Malaria.The differentially expressed genes visualization protein-protein interaction network shows the top 10 genes including Ifng,Grb2,CCR7,CTLA4,CXCR5,Foxp3,kit,PRF1,CD5 and klrg1.Conclusion:These findings showed that moxa cone moxibustion can alleviate chemotherapy-induced diarrhea by reducing the loss of large peritoneal macrophages and B1 cells in the peritoneal cavity,possibly through up-regulating inflammatory bowel disease signaling pathway via interferon-gamma to regulate the survival and function of large peritoneal macrophages and B1 cells.

Oleanolic acid inhibits colon cancer cell stemness and reverses chemoresistance by suppressing JAK2/STAT3 signaling pathway

Background:Oleanolic acid(OA),a pentacyclic triterpenoid exhibiting specific anti-cancer properties and highly effective antioxidant activity,was isolated from traditional Chinese medicinal herbs.Conversely,the OA that impacts colon cancer(CC)cells and its underlying mechanisms remain poorly understood.Methods:The cytotoxic effect of OA alone or OA-5-Fluorouracil(5-FU)combination on normal and CC cells was analyzed by methyl thiazolyl diphenyl-tetrazolium bromide(MTT).Then,the impact of OA on CC cell lines(LoVo and HT-29)proliferation and stemness were measured using colon formation and tumorsphere formation assays.Octamer-binding transcription factor 4(Oct4),Prominin-1(CD133),Nanog,and transcription factor SOX-2(SOX2)are cell stemness-related indicators whose expression was assessed usingfluorescence qPCR assay,Western blotting,and immunohistochemistry.The effect of OA on the proliferative potency of CC cells was evaluated using an in vivo model.Results:The stem-like characteristics and clone production of colon cancer cells were markedly reduced by OA alone or in combination with OA-5-FU.Moreover,OA increases the susceptibility of CC cells to 5-FU by blocking the cell stemness-related markers(CD133,Nanog,SOX2,and Oct4)expression levels both in vitro and in vivo,as well as by inactivating the activator of transcription 3(STAT3 signaling)and Janus kinase 2/signal transducer(JAK2).Conclusion:Thesefindings imply that oleanolic acid,both in vitro and in vivo,suppresses the JAK2/STAT3 pathway,which in turn reverses chemoresistance and decreases colon cancer cell stemness.Therefore,by reducing the recommended amount of 5-FU,this strategy may improve chemotherapeutic effectiveness and minimize undesired side effects.

The relationship between the distribution of HBcAg in liver cells and the pathological manifestations of the liver in 429 HBeAg-positive chronic HBV-infected individuals

Background:The natural history of chronic HBV infection is typically characterized by four stages:the immune tolerance period,the immune clearance period,the immune control period,and the immune escape period.These stages are associated with the distribution of HBcAg in liver cells;however,this relationship remains a topic of broad debate within the field of liver disease.To objectively and quantitatively measure the intracellular distribution of HBcAg,this paper aims to design a method referred to as the“layered evaluation method”and to examine its validation.Methods:The distribution of HBcAg in liver cells is assessed using Image Pro Plus image processing software,along with calculations of cytoplasmic and nuclear positive staining rates.Results:The findings indicate that the highest proportion of patients exhibited a positive cytoplasmic expression rate ranging from 0-2.5%.More than 40% of the total sample was categorized within the 0-2.5% positive nuclear expression range.The HBcAg cytoplasmic positive staining rates were classified into five levels:a cytoplasmic HBcAg positive staining rate of less than 0.05% is designated as level 0,indicating negative expression;a staining rate between 0.05% and 5% is classified as level 1;a rate from 5% to less than 10% is classified as level 2;a rate from 10% to less than 20% is classified as level 3;and a nuclear positivity rate exceeding 20% is classified as level 4.Conclusion:The inflammatory activity grade in these patients was positively correlated with the cytoplasmic distribution of HBcAg.Furthermore,the nuclear distribution rate of HBcAg was significantly higher in the G3 group compared to the other groups.

Progress in building clinically relevant patient-derived tumor xenograft models for cancer research

Patient-derived tumor xenograft(PDX)models,a method involving the surgical extraction of tumor tissues from cancer patients and subsequent transplantation into immunodeficient mice,have emerged as a pivotal approach in translational research,particularly in advancing precision medicine.As the first stage of PDX development,the patient-derived orthotopic xenograft(PDOX)models implant tumor tissue in mice in the corresponding anatomical locations of the patient.The PDOX models have several advantages,including high fidelity to the original tumor,heightened drug sensitivity,and an elevated rate of successful transplantation.However,the PDOX models present significant challenges,requiring advanced surgical techniques and resourceintensive imaging technologies,which limit its application.And then,the humanized mouse models,as well as the zebrafish models,were developed.Humanized mouse models contain a human immune environment resembling the tumor and immune system interplay.The humanized mouse models are a hot topic in PDX model research.Regarding zebrafish patient-derived tumor xenografts(zPDX)and patient-derived organoids(PDO)as promising models for studying cancer and drug discovery,zPDX models are used to transplant tumors into zebrafish as novel personalized medical animal models with the advantage of reducing patient waiting time.PDO models provide a cost-effective approach for drug testing that replicates the in vivo environment and preserves important tumor-related information for patients.The present review highlights the functional characteristics of each new phase of PDX and provides insights into the challenges and prospective developments in this rapidly evolving field.

Ultrasound-guided carotid angioplasty and stenting in a patient with iodinated contrast allergy:A case report

BACKGROUND Ischemic stroke is an entity with high incidence,morbidity,and mortality rates.Carotid artery stenosis is an important and independent risk factor for ischemic stroke.The three current approaches for treating carotid artery stenosis are drug treatment,carotid endarterectomy(CEA),carotid angioplasty and stenting(CAS).The approach is chosen based on the degree of stenosis.CEA or CAS could have been chosen for the current patient,who had severe carotid stenosis and an iodinated contrast allergy.After thoroughly communicating with the patient,the patient chose CAS for treatment.Therefore,we performed ultrasound-guided CAS to avoid the use of iodinated contrast.CASE SUMMARY The main symptoms of the patient were numbness and weakness of the left limb.Computed tomography angiography of the head and neck at another hospital indicated multiple sites of stenosis in the arteries of the head and neck.The patient requested CAS for treatment but was allergic to iodinated contrast media.Thus,routine digital subtraction angiography(DSA)with iodinated contrast could not be used for the procedure.The diagnosis of this patient was as follows:(1)Right parietal lobe cerebral infarction;(2)multiple sites of stenosis in the arteries of the head and neck(severe stenosis of the right internal carotid artery,severe stenosis of the right subclavian artery);(3)right subclavian steal syndrome;and(4)hypertension(stage 3,high risk).The interventions included routine treatment for cerebral infarction,oral administration of clopidogrel(75 mg qd)and aspirin(100 mg qd),ultrasound-guided CAS,and postoperative follow-up.Postoperative color Doppler ultrasound and cerebrovascular magnetic resonance angiography of the carotid artery showed good vascular recovery,and the postoperative follow-up indicated a good prognosis.CONCLUSION This case study suggests that ultrasound-guided endovascular treatment is a potential option for patients with contraindications to the iodinated contrast agents used in DSA-guided surgery,although excellent surgical operating skills are needed.

Aryl hydrocarbon receptor nuclear translocator 2 as a prognostic biomarker and immunotherapeutic indicator for clear cell renal cell carcinoma

Background:In many cancer types,aryl hydrocarbon receptor nuclear translocator 2(ARNT2)has been found to be associated with tumor cell proliferation and prognosis.However,the role of ARNT2 in clear cell renal cell carcinoma(ccRCC)has not been completely elucidated.In this study,the potential role of ARNT2 in ccRCC development was characterized.Methods:A pan-cancer dataset(TCGA-TARGET-GTEx)was accessed from UCSC Xena Data Browser.ARNT2 expression in normal and tumor samples was compared.Univariate Cox regression was performed to evaluate the prognostic value of ARNT2.Single sample gene set enrichment analysis(ssGSEA)was used to estimate the enrichment of functional pathways and gene signatures.CIBERSORT and ESTIMATE methods evaluated the immune infiltration.The ARNT2 expression was determined in ccRCC tissue and cell lines using RT-qPCR and Western blot.Results:ARNT2 expression was significantly dysregulated in 23 out of 30 cancer types.Pan-cancer data revealed a strong correlation between ARNT2 expression and immune modulators,immune cell infiltration,and genomic alternations.In ccRCC patients,the low-ARNT2 expression group had higher immune infiltration,CD8 T cells,and programmed cell death ligand 1 expression,as well as higher enrichment score of immunotherapeutic predictors than those in the high-ARNT2 expression group.Low-ARNT2 expression group was more responsive to immunotherapy.Moreover,low ARNT2 expression was observed in ccRCC tissue and cell lines.Conclusions:Dysregulated ARNT2 expression is involved in cancer development and the modulation of the immune microenvironment.ARNT2 can be potentially used as a prognostic indicator and an immunotherapeutic indicator for ccRCC.

Therapeutic effect of autologous concentrated growth factor on lower-extremity chronic refractory wounds:A case report

BACKGROUND Management of chronic refractory wounds is one of the toughest clinical challenges for surgeons.Because of poor blood supply,less tissue coverage,and easy exposure,the lower leg is a common site for chronic refractory wounds.The current therapeutic regimens often lead to prolonged hospital stay and higher healthcare costs.Concentrated growth factor(CGF)is a novel blood extract that contains various growth factors,platelets,and fibrins to promote wound healing process.However,there has been little research reported on the treatment of lower extremity wounds with CGF.CASE SUMMARY A 37-year-old man,without any past medical history,presented an ulcerated chronic wound on his right lower leg.The skin defect exhibited clear boundaries,with a size of 2.0 cm×3.5 cm.The depth of wound was up to the layer of deep fascia.Staphylococcus aureus was detected by bacterial culture.The final diagnosis was right lower extremity ulcers with infection.Cefathiamidine,silver sulfadiazine,and mupirocin cream were applied to control the infection.CGF gel was prepared from the patient’s blood sample,and was used to cover the wound after thorough debridement.The skin wound was successfully healed after three times of CGF treatment.CONCLUSION CGF displays an excellent wound healing promoting effect in patients with lowerextremity chronic refractory wounds.

Bergapten attenuates D-galactose-induced immunosenescence in BALB/c mice

OBJECTIVE Bergapten(BG),is a furanocoumarin derived from herbal and citrus extracts can act as antioxidant and selective anticancer agents.The current study aimed to investigate whether bergapten would attenuate immunosenescence and to exploreits immunomodulatory effects on immune responses in D-galactose-induced aging BALB/c mice.METHODS Firstly,mice were given D-galactose(180 mg·kg^(-1)) subcutaneous injections for 30 d.To evaluate the establishment of the agingrelated effect in mice,serum samples of BALB/c mice were collected from tail vein.Aging BALB/c mice were freely divided into three groups:negative control group received 1% Tween 80 solution only,named D-gal group.Positive groups were received BG administration at the dose of 20 and 100 mg·kg^(-1),named D-gal+BG(20) group and D-gal+BG(100) group,respectively.Effects of bergapten on T lympho.cyte proliferation and flow cytometry were assessed by using the splenic cell suspension.Enzyme linked immunospot kits were used to quantitatively determine interferon-γ(IFN-γ) and interleukin-4(IL-4)levels of the isolated serum.Immunophenotype was determined by using mixture of antibodies includ.ing anti-CD3,anti-CD4,and anti-CD8.RESULTS Bergapten(20 mg·kg^(-1)) therapy can modulate immu.nity against viral epidemics and attenuate aging-induced immune deficiency(P<0.01),which was correlat.ed with the decline in the activation of the Th and Tc responses in D-galactose induced aging BALB/c mice.According to the in vivo results,bergapten exposure up-regulated the secretion of IFN-γ and IL-4 in T-helper 1(Th1) and T helper 2(Th2) cells(P<0.05,P<0.01).Additionally,BG(20 mg·kg^(-1)) restored antigen-specific CD4+ and CD8+ T cells in aging models(P<0.05,P<0.01),which may help to curing chronic infections.CONCLUSION The beneficial effect of bergapten in D-galactose induced aging BALB/c mice may be due to the Th and Tc responses activation.

An enriched environment reduces hippocampal inflammatory response and improves cognitive function in a mouse model of stroke

An enriched environment is used as a behavio ral intervention therapy that applies sensory,motor,and social stimulation,and has been used in basic and clinical research of va rious neurological diseases.In this study,we established mouse models of photothrombotic stroke and,24 hours later,raised them in a standard,enriched,or isolated environment for 4 weeks.Compared with the mice raised in a standard environment,the cognitive function of mice raised in an enriched environment was better and the pathological damage in the hippocampal CA1 region was remarkably alleviated.Furthermore,protein expression levels of tumor necrosis factor receptor-associated factor 6,nuclear factorκB p65,interleukin-6,and tumor necrosis factorα,and the mRNA expression level of tumor necrosis factor receptor-associated factor 6 were greatly lower,while the expression level of miR-146a-5p was higher.Compared with the mice raised in a standard environment,changes in these indices in mice raised in an isolated environment were opposite to mice raised in an enriched environment.These findings suggest that different living environments affect the hippocampal inflammatory response and cognitive function in a mouse model of stro ke.An enriched environment can improve cognitive function following stroke through up-regulation of miR-146a-5p expression and a reduction in the inflammatory response.

Goodpasture syndrome and hemorrhage after renal biopsy: A case report

BACKGROUND Goodpasture syndrome(GS) is a rare disease, the morbidity of which is estimated to be 0.5-0.8 per million per year. Hemorrhage is the most serious complication in renal biopsy. Despite the fact that both GS and hemorrhage after renal biopsy are rare, it has not been reported that they are likely to occur in the same patient.CASE SUMMARY A 30-year-old man with diffuse pulmonary hemorrhage and rapid progressive renal function caused by anti-glomerular basement membrane disease presented atypical symptoms without hemoptysis, accompanied by life-threatening hypoxemia. Plasmapheresis was performed, and glucocorticoids and cyclophosphamide were administered. The patient started to show signs of improvement. Percutaneous renal biopsy is an appropriate diagnostic measure that is commonly safe, but this patient experienced hemorrhage after operation,thus necessitating embolization of the renal artery to stop the bleeding. The patient’s condition was improved, and the serum anti-glomerular basement membrane antibody level was 106 AU/m L(normal range: < 24 AU/m L) and slowly decreased. His discharge medications were oral daily prednisone(30 mg)and continued maintenance hemodialysis.CONCLUSION GS is a rare organ-specific autoimmune disease that is invariably ubiquitous in the lung and kidney areas. Renal biopsy is the appropriate procedure for the treatment of GS disease, although it is an invasive measure.

Systemic lupus erythematosus and antineutrophil cytoplasmic antibody-associated vasculitis overlap syndrome in a 77-year-old man: A case report

BACKGROUND Systemic lupus erythematosus(SLE)and antineutrophil cytoplasmic antibodyassociated vasculitis(AAV)are classically thought to cause renal impairment and small vessel vasculitis with different pathophysiologies.Their overlap constitutes a rare rheumatologic disease.To date,only dozens of such cases with biopsyproven glomerulonephritis have been reported worldwide typically in women of childbearing age.Here,we present a unique clinical case due to its rarity and individualized treatment of a Chinese man in his eighth decade of life.CASE SUMMARY A 77-year-old man was admitted to several hospitals for shortness of breath and received nonspecific treatments over the past 3 years.As his symptoms were not completely relieved,he visited our hospital for further treatment.Laboratory examinations revealed kidney dysfunction,severe anaemia,hypocomplementemia,glomerular proteinuria,and microscopic haematuria.Antinuclear antibodies,as well as anti-dsDNA antibodies,were positive.Computed tomography of the chest showed right pleural effusion.Renal biopsy was performed,and histology suggested crescentic glomerulonephritis,pauci-immune type.After treatment with plasmapheresis,glucocorticoid,and cyclophosphamide,the disease was in remission,and the patient remained in a stable condition for over 3 years post-hospital discharge.CONCLUSION Due to its complexity and rarity,SLE and AAV overlap syndrome is easily misdiagnosed.An accurate diagnosis and treatment at the earliest stage may significantly improve the condition and reduce irreversible organ injury.

Ameliorative effect of berberine on high-fat diet/streptozotocin-induced early diabetic nephropathy in rats

OBJECTIVE To investigate possible protective effect of berberine,an isoquinoline alkaloid,is the major active constituent of Rhizoma coptidis and Cortex phellodendri,on high-fat diet/streptozotocin-induced early diabetic nephropathy in rats and various mechanisms underlie this effect.METHODS The diabetic rat model was generated by a single intraperitoneal injection of streptozotocin(STZ,50 mg·kg-1).Diabetic rats were randomlyassigned into the following five groups:control,DN,losartan(30 mg·kg-1·d-1),berberine(100,200 mg·kg-1·d-1).Berberine and losartan were given intragastricly for nine weeks.At the end of the experiment,urine of each group was collected in a 24 h period.Rats were weighed and then sacrificed.Plasma and kidneys were collected.The levels of blood glucose,creatinine(Cr),triglycerides(TG),total cholesterol(TCH)and malondialdehyde(MDA)in serum were determined using commercial kits according to the manufacturer′s instructions.Transforming growth factor(TGF)-β1and intracellular adhesion molecule-1(IAM-1)mR NA levels were evaluated by RT-PCR.The renal histopathology was observed by light microscopy.Further biochemical analysis of IKKβ1 and p65(nucleus/cytoplasm)was provided using Western blotting techniques.RESULTS Our study has demonstrated that berberine has various pharmacological activities.The DN rats had significantly higher kidney/body weight ratio(17.4±1.4)mg·g-1,and berberine treatment could reduce this ratio change 13.6±0.6 and(11.6±0.8)mg·g-1,respectively;glucose control still remains the only disease-modifying therapy for diabetic complications,FBG was also recorded in the experiment.The findings reveal that the DN group showed a significantly higher glucose level(28.67±2.78)mmol·L-1.Treatment with8 weeks of berberine improved these parameters except blood glucose〔(18.67±2.59)mmol·L-1and 16.45±1.80 vs(28.67±2.78)mmol·L-1:plasma levels of urea nitrogen(15.67±2.48)mmol·L-1and 14.45±2.40 vs(12.26±2.40)mmol·L-1〕;plasma levels of 24 h urine albuminuria〔30.48±1.56 and 25.72±2.24 vs(15.26±0.12)μg·d-1〕;based on these results,berberine supposed to improve renal functions in diabetic rats.Berberine also ameliorated the inflammatory changes of DN in diabetic animals;levels of TG,TCH and MDA in berberine-treatment rats were significantly lower compared with those in the DN group:TG〔2.78±0.24 and 2.45±0.36 vs(5.20±0.60)mmol·L-1〕;TCH〔4.26±0.46 and 3.74±0.68 vs(6.26±0.50)mmol·L-1〕;MDA〔4.94±1.19 and 4.28±0.64 vs(4.28±0.64)nu·mL-1〕.Chronic inflammation,as is observed in diabetes,is associated with increased production of TGF-β1and IAM-1.Compared with the renal tissues of DN group,TGF-β1and IAM-1 gene expressions in berberine treated groups were reduced at the dose levels(100 and 200 mg·kg-1).And TGF-β1and IAM-1levels in berberine treated groups were reduced in a dosedependent manner:Relative expression of TGF-β1mR NA level(3.56±0.28 and 3.12±0.14 vs 5.12±0.44);Relative expression of IAM-1 mR NA leve(l1.78±0.56 and 1.42±0.24vs 4.36±0.35).Research finds that the NF-κB signaling pathway is activated in the renal tissue of diabetic mice and berberine inhibits activation of the NF-κB pathway:staining score for IKKβ1(4.34±0.26 and 3.82±0.24 vs 6.23±0.76),staining score for p65(2.34±0.26 and 1.74±0.78 vs 6.23±0.24)in nucleus and staining score for p65(7.21±0.13 and8.15±0.45 vs 4.23±0.54)in cytoplasm.CONCLUSION In this field,berberine suppresses the increased expression of p65 in the nucleus and decreases it in cytoplasm,which leads to the inhibition of the NF-κB pathway.These changes will result in decreasing the transcription and translation of many inflammatory mediators,such as TGF-β1and IAM-1.Additionally,these changes decrease the number of inflammatory cells and mononuclear macrophage infiltration into glomeruli and renal interstitium.These results indicated that berberine can protect the kidney of STZ-diabetic rats by reducing the expression of TGF-β1and IAM-1 in the renal tubulointerstitium.And we propose that berberinemayfunction as an effective therapeutic agent for diabetic nephropathy and attenuate the progression of renal injury.

Cerebral venous sinus thrombosis in pregnancy: A case report

BACKGROUND Cerebral venous thrombosis(CVT)is a rare but life-threatening disease in pregnant women.Anticoagulation is the first-line therapy for CVT management.However,some patients have poor outcomes despite anticoagulation.Currently,the endovascular treatment of CVT in pregnant women remains controversial.We report a rare case of CVT in a pregnant woman who was successfully treated with two stent retriever devices.CASE SUMMARY The patient was a 29-year-old pregnant woman.She was first diagnosed with hyperemesis gravidarum due to severe nausea and vomiting for one week.As the disease progressed,she developed acute left hemiplegia.Imaging confirmed the diagnosis of superior sagittal sinus,right transverse sinus and sinus sigmoideus thrombosis.As anticoagulant therapy was ineffective,she underwent thrombectomy.After the mechanical thrombectomy,her headache diminished.Three weeks later,the patient was completely independent.At a 3-mo follow-up,no relapse of symptoms was observed.CONCLUSION Mechanical thrombectomy may be an effective alternative therapy for CVT in pregnant women if anticoagulation therapy fails.

PPARβ expression in rectus abdominis and abdominal subcutaneous fat of patients with gestational diabetes mellitus and its relationship with glucolipid metabolism

Objective:To study the relationship between peroxisome proliferator-activated receptorβ(PPARβ) expression in rectus abdominis as well as abdominal subcutaneous fat of patients with gestational diabetes mellitus (GDM) and glucolipid metabolism.Methods:The pregnant women who received routine antenatal care and planned to receive selective caesarean section in Obstetrics Department of our hospital between May 2012 and March 2016 were retrospectively analyzed, and 74 healthy pregnant women and 58 pregnant women with GDM were screened and included in the control group and gestational diabetes mellitus group (GDM group) respectively. Rectus abdominis and abdominal subcutaneous fat were collected during Cesarean section to determine the expression of PPARβ was measured;peripheral blood was collected at middle-late pregnancy to determine the content of blood glucose metabolism and lipid metabolism indexes as well as adipocytokines.Results:PARβ mRNA expression and protein expression in rectus abdominis and abdominal subcutaneous fat of GDM group were significantly lower than those of control group (P<0.05);homeostasis model assessment insulin secretion index (HOMA-β), homeostasis model assessment insulin resistance (HOMA-IR) and OGTT glucose curve (AUCG) levels as well as serum low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), cholesterol (TC), Leptin, Resistin and Chemerin content of GDM group were significantly higher than those of control group (P<0.05) while early insulin secretion index (ΔI30/ΔG30) and insulin sensitive index composite (ISIcomp) levels as well as serum high-density lipoprotein cholesterol (HDL-C), Omentin-1 and Omentin-1 and adiponectin (ADPN) content were significantly lower than those of control group (P<0.05);PARβ mRNA expression and protein expression were negatively correlated with HOMA-β, HOMA IR, area under the AUCG, LDL-C, TG, TC, Leptin, Resistin and Chemerin, and positively correlated withΔI30/ΔG30, ISIcomp, HDL-C, and ADPN.Conclusions:PPARβ expression significantly decreases in rectus abdominis and abdominal subcutaneous fat of pregnant womepn with GDM and it is closely related to the abnormal glucolipid metabolism in pregnant women with GDM.

Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits in a young woman: A case report

BACKGROUND Proliferative glomerulonephritis with monoclonal immunoglobulin G(IgG)deposits(PGNMID)is a newly recognized rare disease.The renal pathology is characterized by prominent manifestations of membranous hyperplasia,which are easy to misdiagnose.The clinical symptoms are severe.Massive proteinuria and hypoproteinemia are conspicuous,and most patients are accompanied by renal insufficiency and microscopic hematuria.CASE SUMMARY A 27-year-old woman was admitted to a hospital for macroscopic hematuria and proteinuria 4 years prior,and renal biopsy in the hospital suggested moderate-tosevere mesangial proliferating glomerulonephritis(MsPGN).She had taken a glucocorticoid,cyclophosphamide,mycophenolate mofetil,and other treatments and achieved brief partial remission.Recently,the patient visited our hospital due to massive proteinuria.Repeated renal biopsy and re-evaluation of the first biopsy obtained 4 years previously revealed monoclonal immunoglobulin deposition in the glomeruli.A bone marrow examination was performed to exclude hematologic malignancy,and a diagnosis of PGNMID was established.The patient showed remission after four cycles of a bortezomib+cyclophosphamide+dexamethasone scheme.CONCLUSION PGNMID is usually misdiagnosed as MsPGN or membranoproliferative glomerulonephritis.Although it often occurs in middle-aged and elderly individuals,it cannot be readily excluded in young people,even when serum immunofixation electrophoresis is negative.IgG subtype and light chain staining are necessary when this disease is highly suspected.An accurate diagnosis at the earliest stage may avoid the overuse of glucocorticoids and immunosuppressants.

Study on the relationship between the expression of NFκB1 and LncRNA-PACER in peripheral blood mononuclear cells of patients with pulmonary tuberculosis

Objective: To investigate the expression relationship between nuclear transcription factor kappa B1 (NFκB1) and long non-coding RNA PACER (LncRNA-PACER) in peripheral blood mononuclear cells (PBMCs) of patients with pulmonary tuberculosis. Methods: From February 2018 to March 2019, 40 patients with pulmonary tuberculosis (tuberculosis group) and 40 healthy persons (control group) were collected, the levels of TNF-α, IL-6 and IL-8 in serum were detected by enzyme-linked immunosorbent assay (ELISA);the expressions of LncRNA-PACER and NFκB1 mRNAs in PBMCs were detected by real-time fluorescence quantitative PCR;Western blot was used to detect the expressions of NFκB1 and COX 2 in PBMCs;Pearson method was used to analyze the expressions of LncRNA-PACER and NFκB1 in PBMCs of patients with pulmonary tuberculosis, and the expressions of LncRNA-PACER and NFκB1 in PBMCs of patients with pulmonary tuberculosis were analyzed. Results: Compared with the control group, the expressions of TNF-α, IL-6 and IL-8 in the serum of patients with pulmonary tuberculosis was significantly increased (P<0.05), and the expressions of LncRNA-PACER, NFκB1 mRNAs, proteins and COX-2 protein in PBMCs were significantly increased (P<0.05). The expressions of LncRNA-PACER and NFκB1 proteins in PBMCs were related to the number of pulmonary lesions and pulmonary cavity (P<0.05), and there was a positive correlation between the expression of LncRNA-PACER and the expression of NFκB1 mRNA in PBMCs of patients with pulmonary tuberculosis (r = 0.873, P<0.05). Conclusions: The expressions of NFκB1 and LncRNA-PACER in PBMCs of patients with pulmonary tuberculosis are significantly increased, they are positively correlated and both of them are related to the occurrence and development of pulmonary tuberculosis.

To set up a logistic regression prediction model for hepatotoxicity of Chinese herbal medicines based on the efficacy of Chinese herbal medicines

In our previous research,a logistic regression prediction model for hepatotoxicity of Chinese herbal medicines based on the four properties,five flavors and channel tropism has been successfully established.However,could Chinese herbal medicines efficacy also be applied to predict the hepatotoxicity of Chinese herbal medicines?Therefore,a logistic regression prediction model for hepatotoxicity of Chinese herbal medicines based on Chinese herbal medicines efficacy has been tentatively set up to study the correlations of hepatotoxic and nonhepatotoxic Chinese herbal medicines with efficacy by using a chi-square test for two-way unordered categorical data.Logistic regression prediction model was established and the accuracy of the prediction by this model was evaluated.It has been found that the hepatotoxicity and nonhepatotoxicity of Chinese herbal medicines were weakly related to the efficacy,and the coefficient was 0.295.There were 20 variables from Chinese herbal medicines efficacy analyzed with unconditional logistic regression,and 6 variables,rectifying Qi and relieving pain,clearing heat and disinhibiting dampness,invigorating blood and stopping pain,invigorating blood and relieving swelling,killing worms and relieving fright were chosen to establish the logistic regression prediction model,with the optimal cutoff value being 0.250.Dissipating cold and relieving pain(DCRP),clearing heat and disinhibiting dampness,invigorating blood and relieving pain(IBRP),invigorating blood and relieving swelling,killing worms,and relieving fright were the variables to affect the hepatotoxicity and the established logistic regression prediction model had predictive power for hepatotoxicity of Chinese herbal medicines to a certain degree.

Astragalus Polysaccharide Enhances Voriconazole Metabolism under Inflammatory Conditions through the Gut Microbiota

Background and Aims:Voriconazole(VRC),a widely used antifungal drug,often causes hepatotoxicity,which presents a significant clinical challenge.Previous studies demonstrated that Astragalus polysaccharide(APS)can regulate VRC metabolism,thereby potentially mitigating its hepatotoxic effects.In this study,we aimed to explore the mechanism by which APS regulates VRC metabolism.Methods:First,we assessed the association of abnormal VRC metabolism with hepatotoxicity using the Roussel Uclaf Causality Assessment Method scale.Second,we conducted a series of basic experiments to verify the promotive effect of APS on VRC metabolism.Various in vitro and in vivo assays,including cytokine profiling,immunohistochemistry,quantitative polymerase chain reaction,metabolite analysis,and drug concentration measurements,were performed using a lipopolysaccharideinduced rat inflammation model.Finally,experiments such as intestinal biodiversity analysis,intestinal clearance assessments,and Bifidobacterium bifidum replenishment were performed to examine the ability of B.bifidum to regulate the expression of the VRC-metabolizing enzyme CYP2C19 through the gut–liver axis.Results:The results indicated that APS does not have a direct effect on hepatocytes.However,the assessment of gut microbiota function revealed that APS significantly increases the abundance of B.bifidum,which could lead to an anti-inflammatory response in the liver and indirectly enhance VRC metabolism.The dual-luciferase reporter gene assay revealed that APS can hinder the secretion of pro-inflammatory mediators and reduce the inhibitory effect on CYP2C19 transcription through the nuclear factor-B signaling pathway.Conclusions:The study offers valuable insights into the mechanism by which APS alleviates VRC-induced liver damage,highlighting its immunomodulatory influence on hepatic tissues and its indirect regulatory control of VRC-metabolizing enzymes within hepatocytes.

Dual stimulus responsive borosilicate glass(BSG)scaffolds promote diabetic alveolar bone defectsrepair by modulating macrophage phenotype

The regeneration of alveolar bone is still clinical challenge,particularly accompanied with diabetes,causing metabolic disorder with a protracted low-grade inflammatory phenotype.As a result,the anticipated loading of biomaterials is highly suspicious in spontaneous modulation of cells function,which is mostly disturbed by constant inflammation.In this study,we developed glucose and hydrogen peroxide dual-responsive borosilicate glass(BSG)scaffolds loaded with epigallocatechin gallate(EGCG)to synergistically modulate the abnormal inflammation of diabetic alveolar bone defects.It was found that the release of EGCG by BSG could directly regulate the shift of macrophages from M1 to the M2 phenotype by promoting autophagy and lessening the inhibition of autophagic flux.Moreover,EGCG can also indirectly regulate the polarization phenotype of macrophages by reducing the activation of NF-κb in stem cells and restoring its immunoregulatory capacity.Therefore,the addition of EGCG to BSG scaffold in diabetes allows for a more striking modulation of the macrophage phenotype in a timely manner.The altered macrophage phenotype reduces local inflammation and thus increases the ability to repair diabetic alveolar bone,showing promise for the treatment of alveolar defect in diabetic patients.

Spontaneous immunomodulation and regulation of angiogenesis and osteogenesis by Sr/Cu-borosilicate glass (BSG) bone cement to repair critical bone defects

Injectable bone biomaterials like bone cement should be designed and fabricated with certain biological criteria,which include:1)recruitment and polarization of the macrophages from M1(pro-inflammatory)to M2(anti-inflammatory)phenotype,2)enhance vascularization,and 3)activate osteogenic differentiation of bone marrow-derived stem cells to promote bone healing.So far,no injectable biomaterials could spontaneously regulate the entire bone healing process that involves inflammation,angiogenesis,and osteogenesis.Therefore,in this study,we designed bone cement comprised of strontium and copper-incorporated borosilicate glass(Sr/Cu-BSG)in the liquid phase of chitosan to modulate bone healing.In vitro studies showed that the controlled release of Sr and Cu ions up-regulated anti-inflammatory genes(IL-1Ra and TGF-β1)while down-regulating pro-inflammatory genes(IL-1βand IL-6)in macrophages at 3 days.Sr and Cu ions also increased the expressions of angiogenic genes(VEGF and bFGF)in HUVECs at 5 days and osteogenic genes(Runx-2,OCN,and OPN)in hBMSCs at 7,14,and 21 days.5Sr3Cu-BSG bone cement exhibited the best anti-inflammatory,angiogenic,and osteogenic properties among the bone cement groups with different Sr and Cu ratios.Short-term and long-term implantation of Sr/Cu-BSGs in femoral condylar bone defects of rats and rabbits confirmed the in vitro results,where the degradation rate of Sr/Cu-BSG matched the bone healing rate.Similar to in vitro,the 5Sr3Cu-BSG group also showed the highest bone formation in vivo.Excellent physical and chemical properties,along with its bone repairing ability,make the Sr/Cu-BSG bone cement a good candidate biomaterial for treating bone defects.