Global trends in publications regarding macrophages-related diabetic foot ulcers in the last two decades

BACKGROUND Diabetic foot ulcers(DFUs)are one of the most severe and popular complications of diabetes.The persistent non-healing of DFUs is the leading cause of amputation,which causes significant mental and financial stress to patients and their families.Macrophages are critical cells in wound healing and perform essential roles in all phases of wound healing.However,no studies have been carried out to systematically illustrate this area from a scientometric point of view.Although there have been some bibliometric studies on diabetes,reports focusing on the investigation of macrophages in DFUs are lacking.AIM To perform a bibliometric analysis to systematically assess the current state of research on macrophage-related DFUs.METHODS The publications of macrophage-related DFUs from January 1,2004,to December 31,2023,were retrieved from the Web of Science Core Collection on January 9,2024.Four different analytical tools:VOSviewer(v1.6.19),CiteSpace(v6.2.R4),HistCite(v12.03.07),and Excel 2021 were used for the scientometric research.RESULTS A total of 330 articles on macrophage-related DFUs were retrieved.The most published countries,institutions,journals,and authors in this field were China,Shanghai Jiao Tong University of China,Wound Repair and Regeneration,and Aristidis Veves.Through the analysis of keyword co-occurrence networks,historical direct citation networks,thematic maps,and trend topics maps,we synthesized the prevailing research hotspots and emerging trends in this field.CONCLUSION Our bibliometric analysis provides a comprehensive overview of macrophage-related DFUs research and insights into promising upcoming research.

Self-assembly of differentiated dental pulp stem cells facilitates spheroid human dental organoid formation and prevascularization

BACKGROUND The self-assembly of solid organs from stem cells has the potential to greatly expand the applicability of regenerative medicine.Stem cells can self-organise into microsized organ units,partially modelling tissue function and regeneration.Dental pulp organoids have been used to recapitulate the processes of tooth development and related diseases.However,the lack of vasculature limits the utility of dental pulp organoids.AIM To improve survival and aid in recovery after stem cell transplantation,we demonstrated the three-dimensional(3D)self-assembly of adult stem cell-human dental pulp stem cells(hDPSCs)and endothelial cells(ECs)into a novel type of spheroid-shaped dental pulp organoid in vitro under hypoxia and conditioned medium(CM).METHODS During culture,primary hDPSCs were induced to differentiate into ECs by exposing them to a hypoxic environment and CM.The hypoxic pretreated hDPSCs were then mixed with ECs at specific ratios and conditioned in a 3D environment to produce prevascularized dental pulp organoids.The biological characteristics of the organoids were analysed,and the regulatory pathways associated with angiogenesis were studied.RESULTS The combination of these two agents resulted in prevascularized human dental pulp organoids(Vorganoids)that more closely resembled dental pulp tissue in terms of morphology and function.Single-cell RNA sequencing of dental pulp tissue and RNA sequencing of Vorganoids were integrated to analyse key regulatory pathways associated with angiogenesis.The biomarkers forkhead box protein O1 and fibroblast growth factor 2 were identified to be involved in the regulation of Vorganoids.CONCLUSION In this innovative study,we effectively established an in vitro model of Vorganoids and used it to elucidate new mechanisms of angiogenesis during regeneration,facilitating the development of clinical treatment strategies.

Crosslink among cyclin-dependent kinase 9,ATP binding cassette transporter G2 and Beclin 1 in colorectal cancer

Colorectal cancer(CRC)ranks third in the number of cancers mainly because of the inability to diagnose it at an early stage.The pathogenesis of CRC is complicated,which is the result of the complex interaction of multiple genetic and environmental factors.Currently,one of the main treatments for CRC is chemotherapy.But the primary cause of CRC treatment failure is drug resistance.The expression of cyclin-dependent kinase 9(CDK9)was correlated with elevated autophagy levels in colon cancer,and high expression of CDK9 indicates a poor prognosis in CRC.The incidence of autophagy and the expressions of Beclin 1 and ATP binding cassette transporter G2 are different in left and right colon cancer,and autophagy may be involved in the occurrence of chemotherapy resistance.In this article,the roles of CDK9,ATP binding cassette transporter G2 and Beclin 1 in CRC were elucidated,emphasizing the linkages among them and providing potential therapeutic targets of CRC.

A Prediction Model for Detecting Dysthyroid Optic Neuropathy Based on Clinical Factors and Imaging Markers of the Optic Nerve and Cerebrospinal Fluid in the Optic Nerve Sheath

Objective This study aimed to develop and test a model for predicting dysthyroid optic neuropathy(DON)based on clinical factors and imaging markers of the optic nerve and cerebrospinal fluid(CSF)in the optic nerve sheath.Methods This retrospective study included patients with thyroid-associated ophthalmopathy(TAO)without DON and patients with TAO accompanied by DON at our hospital.The imaging markers of the optic nerve and CSF in the optic nerve sheath were measured on the water-fat images of each patient and,together with clinical factors,were screened by Least absolute shrinkage and selection operator.Subsequently,we constructed a prediction model using multivariate logistic regression.The accuracy of the model was verified using receiver operating characteristic curve analysis.Results In total,80 orbits from 44 DON patients and 90 orbits from 45 TAO patients were included in our study.Two variables(optic nerve subarachnoid space and the volume of the CSF in the optic nerve sheath)were found to be independent predictive factors and were included in the prediction model.In the development cohort,the mean area under the curve(AUC)was 0.994,with a sensitivity of 0.944,specificity of 0.967,and accuracy of 0.901.Moreover,in the validation cohort,the AUC was 0.960,the sensitivity was 0.889,the specificity was 0.893,and the accuracy was 0.890.Conclusions A combined model was developed using imaging data of the optic nerve and CSF in the optic nerve sheath,serving as a noninvasive potential tool to predict DON.

Research Progress on the Association Between Gut Microbiota and Respiratory System Diseases

This paper aims to review the association between gut microbiota and respiratory system diseases, and explore their potential mechanisms and clinical significance. Gut microbiota, as an important microbial ecosystem in the human body, has profound effects on host health. Recent studies have shown that the imbalance of gut microbiota is closely related to the occurrence and development of respiratory system diseases, including asthma, chronic obstructive pulmonary disease (COPD), and pneumonia. We comprehensively analyzed the current research progress and found that gut microbiota may affect respiratory system diseases through various pathways, including immune regulation, inflammatory responses, and airway mucus secretion. Additionally, environmental factors, lifestyle, and dietary habits are also closely related to gut microbiota and respiratory system health. Understanding the relationship between gut microbiota and respiratory system diseases not only helps to reveal the mechanisms of disease occurrence but also provides a theoretical basis for the development of new treatment strategies. Future research should focus on exploring the types and functions of gut microbiota, conducting clinical trials based on this, investigating the effects of gut microbiota modulation on the treatment and prevention of respiratory system diseases, and providing new directions for personalized medicine.

Microglial depletion impairs glial scar formation and aggravates inflammation partly by inhibiting STAT3 phosphorylation in astrocytes after spinal cord injury

Astrocytes and microglia play an orchestrated role following spinal cord injury;however,the molecular mechanisms through which microglia regulate astrocytes after spinal cord injury are not yet fully understood.Herein,microglia were pharmacologically depleted and the effects on the astrocytic response were examined.We further explored the potential mechanisms involving the signal transducers and activators of transcription 3(STAT3)pathway.For in vivo experiments,we constructed a contusion spinal cord injury model in C57BL/6 mice.To deplete microglia,all mice were treated with colony-stimulating factor 1 receptor inhibitor PLX3397,starting 2 weeks prior to surgery until they were sacrificed.Cell proliferation was examined by 5-ethynyl-2-deoxyuridine(EdU)and three pivotal inflammatory cytokines were detected by a specific Bio-Plex Pro^(TM) Reagent Kit.Locomotor function,neuroinflammation,astrocyte activation and phosphorylated STAT3(pSTAT3,a maker of activation of STAT3 signaling)levels were determined.For in vitro experiments,a microglia and astrocyte coculture system was established,and the small molecule STA21,which blocks STAT3 activation,was applied to investigate whether STAT3 signaling is involved in mediating astrocyte proliferation induced by microglia.PLX3397 administration disrupted glial scar formation,increased inflammatory spillover,induced diffuse tissue damage and impaired functional recovery after spinal cord injury.Microglial depletion markedly reduced EdU+proliferating cells,especially proliferating astrocytes at 7 days after spinal cord injury.RNA sequencing analysis showed that the JAK/STAT3 pathway was downregulated in mice treated with PLX3397.Double immunofluorescence staining confirmed that PLX3397 significantly decreased STAT3 expression in astrocytes.Importantly,in vitro coculture of astrocytes and microglia showed that microglia-induced astrocyte proliferation was abolished by STA21 administration.These findings suggest that microglial depletion impaired astrocyte proliferation and astrocytic scar formation,and induced inflammatory diffusion partly by inhibiting STAT3 phosphorylation in astrocytes following spinal cord injury.

Curcumin Recovers Intracellular Lipid Droplet Formation Through Increasing Perilipin 5 Gene Expression in Activated Hepatic Stellate Cells In Vitro

The activation of hepatic stellate cells(HSCs)is a major event during hepatic fibrogenesis.Restoration of intracellular lipid droplet(LD)formation turns the activated HSC back to a quiescent state.Our previous studies have shown that curcumin suppresses HSC activation through increasing peroxisome proliferator-activated receptor,gamma(PPARγ)and 5′adenosine monophosphate-activated protein kinase(AMPK)activities.This study aims at evaluating the effect of curcumin on lipid accumulation in HSCs and hepatocytes,and further elucidating the underlying mechanisms.Now we showed that curcumin increased LD formation in activated HSCs and stimulated the expression of sterol regulatory element-binding protein and fatty acid synthase,and reduced the expression of adipose triglyceride lipase.Exogenous perilin5 expression in primary HSCs promoted LD formation.Perilipin 5 siRNA eliminated curcumin-induced LD formation in HSCs.These results suggest that curcumin recovers LD formation and lipid accumulation in activated HSCs by increasing perilipin 5 gene expression.Furthermore,inhibition of AMPK or PPARy activity blocked curcumin's effect on Plin5 gene expression and LD formation.Our results provide a novel evidence in vitro for curcumin as a safe,effective candidate to treat liver fibrosis.

Comparison of the Tellgenplex HPV DNA test with the PCR-reverse dot blot assay for human papillomavirus genotyping

Objective: To access the performance of the Tellgenplex human papillomavirus(HPV) DNA test compared to the polymerase chain reaction-reverse dot blot(PCR-RDB) assay for the HPV genotyping.Methods: Sixty cervical swab samples were genotyped by the Tellgenplex HPV DNA test and the PCR-RDB assay.The Tellgenplex HPV DNA test and the PCR-RDB assay can detect 26 and 23 HPV genotypes, respectively.Each sample showed discrepancy was genotyped using sequencing.Results: The percent agreement between the two tests ranged from 83.3% to 100.0% according to different genotype.This showed perfect agreement(>0.81) for high-risk HPV genotypes(35, 39, 45, 53, 56, 59, 66, 68, and 82), substantial agreement(>0.65) for high-risk HPV genotypes(16, 18, 33, 52, and 58) and low-risk HPV genotype 43 between the two assays by the kappa analysis.The positive rates of the two assays for frequent HPV genotypes(16, 35, 39, 45, 52, 53, 58, 59, 66, and 82) were not statistically different, but the PCR-RDB assay showed higher positive rates than the Tellgenplex HPV DNA test for HPV genotypes 81(P<0.05).As for more than 10 positive results by the Tellgenplex HPV DNA test and/or the PCR-RDB assay, the PCR-RDB assay showed higher relative sensitivity and specificity than the Tellgenplex HPV DNA test for the three HPV genotypes(16, 52, and 81).All HPV genotypes that can be detected by only the Tellgenplex HPV DNA test(HPV genotypes 44 and 55) were confirmed by sequencing.Conclusions: In conclusion, our results demonstrated that the PCR-RDB assay which can detect more multiple HPV genotypes in each specimen shows higher relative sensitivity and specificity than the Tellgenplex HPV DNA test, which makes it a better option for routine clinical use.

Microbiologic risk factors of recurrent choledocholithiasis postendoscopic sphincterotomy

BACKGROUND Choledocholithiasis is a severe disorder that affects a significant portion of the world’s population.Treatment using endoscopic sphincterotomy(EST)has become widespread;however,recurrence post-EST is relatively common.The bile microbiome has a profound influence on the recurrence of choledocholithiasis in patients after EST;however,the key pathogens and their functions in the biliary tract remain unclear.AIM To investigate the biliary microbial characteristics of patients with recurrent choledocholithiasis post-EST,using next-generation sequencing.METHODS This cohort study included 43 patients,who presented with choledocholithiasis at the Guangdong Second Provincial General Hospital between May and June 2020.The patients had undergone EST or endoscopic papillary balloon dilation and were followed up for over a year.They were divided into either the stable or recurrent groups.We collected bile samples and extracted microbial DNA for analysis through next-generation sequencing.Resulting sequences were analyzed for core microbiome and statistical differences between the diagnosis groups;they were examined using the Kyoto Encyclopedia of Genes and Genomes pathway hierarchy level using analysis of variance.Correlation between the key genera and metabolic pathways in bile,were analyzed using Pearson’s correlation test.RESULTS The results revealed distinct clustering of biliary microbiota in recurrent choledocholithiasis.Higher relative abundances(RAs)of Fusobacterium and Neisseria(56.61%±14.81%vs 3.47%±1.10%,8.95%±3.42%vs 0.69%±0.32%,respectively)and the absence of Lactobacillus were observed in the bile of patients with recurrent disease,compared to that in stable patients.Construction of a microbiological co-occurrence network revealed a mutual relationship among Fusobacterium,Neisseria,and Leptotrichia,and an antagonistic relationship among Lactobacillales,Fusobacteriales,and Clostridiales.Functional prediction of biliary microbiome revealed that the loss of transcription and metabolic abilities may lead to recurrent choledocholithiasis.Furthermore,the prediction model based on the RA of Lactobacillales in the bile was effective in identifying the risk of recurrent choledocholithiasis(P=0.03).CONCLUSION We demonstrated differences in the bile microbiome of patients with recurrent choledocholithiasis compared to that in patients with stable disease,thereby adding to the current knowledge on its microbiologic etiology.

LAG-3 expression on tumor-infiltrating T cells in soft tissue sarcoma correlates with poor survival

Objective: To elucidate the role and prognostic significance of lymphocyte activation-gene-3(LAG-3) in soft tissue sarcoma(STS).Methods: The expression of LAG-3 in patient and matched normal blood samples was analyzed by flow cytometry. The localization and prognostic values of LAG-3^+ cells in 163 STS patients were analyzed by immunohistochemistry. In addition, the expression of tumor-infiltrating CD3^+ T, CD4^+ T, and CD8^+ T cells and their role in the prognosis of STS were evaluated by immunohistochemistry. The effect of LAG-3 blockade was evaluated in an immunocompetent MCA205 fibrosarcoma mouse model.Results: Peripheral CD8^+ and CD4^+ T cells from STS patients expressed higher levels of LAG-3 than those from healthy donors.LAG-3 expression in STS was significantly associated with a poor clinical outcome(P = 0.038) and was correlated with high pathological grade(P < 0.001), advanced tumor stage(P = 0.016). Additionally, LAG-3 expression was highly correlated with CD8^+ T-cell infiltration(r = 0.7034, P < 0.001). LAG-3 was expressed in murine tumor-infiltrating lymphocytes, and its blockade decreased tumor growth and enhanced secretion of interferon-gamma by CD8^+ and CD4^+ T cells.Conclusions: LAG-3 blockade may be a promising strategy to improve the effects of targeted therapy in STS.

Evaluation of sensory function and recovery after replantation of fingertips at ZoneⅠin children

Sensory function is the most significant criterion when evaluating the prognosis of replanted fingers. Current clinical research has focused on surgical techniques and indications for finger replantation; however, few studies have focused on recovery of finger sensory function af- ter replantation. This study retrospectively assessed data of eight patients who had undergone nine Zone I replantations of the fingertips in the First Affiliated Hospital of Sun Yat-sen University of China from July 2014 to January 2016. Variations in the extent of damage, with the residual vessels or nerves in some fingers being too short or even missing, prevented tension-free suture repair in some patients. Thus, re- pair of four of the nine fingertips included arteriovenous anastomosis, the remaining five undergoing arterial anastomosis during replanta- tion of the amputated fingers. Three patients underwent nerve repair, whereas the remaining six cases did not. Fingertip replantations were successful in all eight patients. Compared with the patients without vascular anastomosis, no obvious atrophy was visible in the fingertips of patients who did undergo vascular anastomosis during replantation and their sensory function did recover. Fingertip replantation pro- vides good sensory function and cosmetic outcomes when good artery and vein anastomoses have been created, even when digital nerves have not been repaired.

Suspected SARS-CoV-2 infection with fever and coronary heart disease:A case report

BACKGROUND The coronavirus disease 2019(COVID-19)is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Suspected cases accounted for a large proportion in the early stage of the COVID-19 outbreak.The deviation of the nucleic acid test by throat swab(the current gold standard of COVID-19)caused by variation in sampling techniques and reagent kits and coupled with nonspecific clinical manifestations make confirmation of the suspected cases difficult.Proper management of the suspected cases of COVID-19 is crucial for disease control.CASE SUMMARY A 65-year-old male presented with fever,lymphopenia,and chest computed tomography(CT)images similar to COVID-19 after percutaneous coronary intervention.The patient was diagnosed as having bacterial pneumonia with cardiogenic pulmonary edema instead of COVID-19.This was based on four negative results for throat swab detection of SARS-CoV-2 nucleic acid using reverse transcriptase-polymerase chain reaction assay and one negative result for serological antibody of SARS-CoV-2 with the serological assay.Additionally,the distribution of ground-glass opacities and thickened blood vessels from the CT images differed from COVID-19 features,which further supported the exclusion of COVID-19.CONCLUSION Distinguishing COVID-19 patients from those with bacterial pneumonia with cardiogenic pulmonary edema can be difficult.Therefore,it requires serious identification.

COVID-19 and the digestive system:A comprehensive review

The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)is spreading at an alarming rate,and it has created an unprecedented health emergency threatening tens of millions of people worldwide.Previous studies have indicated that SARS-CoV-2 ribonucleic acid could be detected in the feces of patients even after smearnegative respiratory samples.However,demonstration of confirmed fecal-oral transmission has been difficult.Clinical studies have shown an incidence rate of gastrointestinal(GI)symptoms ranging from 2%to 79.1%in patients with COVID-19.They may precede or accompany respiratory symptoms.The most common GI symptoms included nausea,diarrhea,and abdominal pain.In addition,some patients also had liver injury,pancreatic damage,and even acute mesenteric ischemia/thrombosis.Although the incidence rates reported in different centers were quite different,the digestive system was the clinical component of the COVID-19 section.Studies have shown that angiotensinconverting enzyme 2,the receptor of SARS-CoV-2,was not only expressed in the lungs,but also in the upper esophagus,small intestine,liver,and colon.The possible mechanism of GI symptoms in COVID-19 patients may include direct viral invasion into target cells,dysregulation of angiotensin-converting enzyme 2,immune-mediated tissue injury,and gut dysbiosis caused by microbiota.Additionally,numerous experiences,guidelines,recommendations,and position statements were published or released by different organizations and societies worldwide to optimize the management practice of outpatients,inpatients,and endoscopy in the era of COVID-19.In this review,based on our previous work and relevant literature,we mainly discuss potential fecal-oral transmission,GI manifestations,abdominal imaging findings,relevant pathophysiological mechanisms,and infection control and prevention measures in the time of COVID-19.

Variant rs8400 enhances ALKBH5 expression through disrupting miR-186 binding and promotes neuroblastoma progression

Objective:AlkB homolog 5(ALKBH5)has been proven to be closely related to tumors.However,the role and molecular mechanism of ALKBH5 in neuroblastomas have rarely been reported.Methods:The potential functional single-nucleotide polymorphisms(SNPs)in ALKBH5 were identified by National Center for Biotechnology Information(NCBI)dbSNP screening and SNPinfo software.TaqMan probes were used for genotyping.A multiple logistic regression model was used to evaluate the effects of different SNP loci on the risk of neuroblastoma.The expression of ALKBH5 in neuroblastoma was evaluated by Western blotting and immunohistochemistry(IHC).Cell counting kit-8(CCK-8),plate colony formation and 5-ethynyl-2'-deoxyuridine(EdU)incorporation assays were used to evaluate cell proliferation.Wound healing and Transwell assays were used to compare cell migration and invasion.Thermodynamic modelling was performed to predict the ability of miRNAs to bind to ALKBH5 with the rs8400 G/A polymorphism.RNA sequencing,N6-methyladenosine(mA)sequencing,mA methylated RNA immunoprecipitation(MeRIP)and a luciferase assay were used to identify the targeting effect of ALKBH5 on SPP1.Results:ALKBH5 was highly expressed in neuroblastoma.Knocking down ALKBH5 inhibited the proliferation,migration and invasion of cancer cells.miR-186-3p negatively regulates the expression of ALKBH5,and this ability is affected by the rs8400 polymorphism.When the G nucleotide was mutated to A,the ability of miR-186-3p to bind to the 3'-UTR of ALKBH5 decreased,resulting in upregulation of ALKBH5.SPPI is the downstream target gene of the ALKBH5 oncogene.Knocking down SPP1 partially restored the inhibitory effect of ALKBH5 downregulation on neuroblastoma.Downregulation of ALKBH5 can improve the therapeutic efficacy of carboplatin and etoposide in neuroblastoma.Conclusions:We first found that the rs8400 G>A polymorphism in the m6A demethylase-encoding gene ALKBH5 increases neuroblastoma susceptibility and determines the related mechanisms.The aberrant regulation of ALKBH5 by miR-186-3p caused by this genetic variation in ALKBH5 promotes the occurrence and development of neuroblastoma through the ALKBH5-SPP1 axis.

Morphology and Function of the Aortic Valve after Transcatheter Closure of Ventricular Septal Defect with Aortic Valve Prolapse

Objective:This study aims to evaluate the morphology and function of the aortic valve after transcatheter closure of ventricular septal defect(VSD)with aortic valve prolapse(AVP)abased on clinical and radiological outcomes.Methods:From January 2013 to November 2014,164 consecutive patients(97 males,59.1%)with VSD and AVP were treated by transcatheter closure.The patients were divided into the mild AVP group(n=63),moderate AVP group(n=89)and severe AVP group(n=12).The clinical and radiological outcomes of these patients were analyzed retrospectively.Results:In total,146(89.0%)patients were successfully treated with VSD occluders,including 59/63(93.7%)with mild AVP,80/89(89.9%)with moderate AVP and 7/12(58.3%)with severe AVP.The degree of AVP was ameliorated or disappeared in 39(26.7%)patients,and remained unchanged in 103(70.5%)patients after the intervention.In the 35 patients who initially had trivial-to-moderate aortic regurgitation(AR),the degree of AR was ameliorated or disappeared in 25(71.4%)patients,aggravated from trivial to mild AR in 1(2.9%)patient,and remained unchanged in 9(25.7%)patients.In 111 patients without AR,1(0.9%)patient had mild AR and 24(21.6%)patients had trivial AR after intervention.The depth and width of the prolapsed aortic valve decreased after transcatheter closure of VSD in all three groups.During the 70-month(range,54–77)follow-up period,no patients with AVP and AR needed an aortic valve intervention.Conclusions:Transcatheter closure of VSD with AVP is feasible.The morphology and function of the prolapsed aortic valve improved and remained stable for a long period after intervention.

Characterization of three-dimensional multipotent adipose-derived stem cell spheroids

Human adipose stem cells(hADSCs)are reliable sources for cell therapy.However,the clinical applications are limited by the decrease in activity during in vitro culture.We used a knockout serum replacement(KSR)medium,Eppendorf(EP)tube culture,and a simulated microgravity(SMG)culture system to establish hADSC spheroids.We found that hADSCs aggregated and formed spheroids in the KSR culture medium.The EP tube culture method revealed many biological cell characteristics,such as good cell viabilities,rough surfaces,polar growth,fusion phenomenon,and injectability.The findings show its advantages for hADSCs spherical cultures.When cultured in SMG,hADSC spheroids produced large-scale spheroids.Additionally,confocal examination and viability assays revealed that SMG-cultured hADSC spheroids had higher cell viabilities and looser spherical structures,relative to those cultured in EP tubes.hADSC spheroids in static EP tube culture had tighter structures and more dead cells with rough and irregular surfaces,while hADSC spheroids in dynamic SMG condition exhibited looser structures and better cell viabilities with flat and regular surfaces.Therefore,the KSR media promotes spherical formation by hADSCs,which showed polar growth,fusion,and injectability in vitro.The dynamic SMG culture enhances the formation of a looser structure and better cell viabilities for hADSC spheroids.

Effects of Manshenkangning Prescription on Adenine-induced Renal Interstitial Fibrosis in Rats

[Objectives]To study the protective effects of Manshenkangning Prescription on adenine-induced renal interstitial fibrosis in rats,and explore the possible mechanism.[Methods]Sixty Wistar male rats were divided into normal group,model group,control group(administered with 10 mg/(kg·d)losartan)and high,medium and low dose experimental groups(30,15,7.5 mg/(kg·d)Manshenkangning).The rat models of renal interstitial fibrosis were induced by intragastric administration of adenine(250 mg/(kg·d)).After 2 h,the above drugs were administered intragastrically for 21 consecutive days and the administration time was 30 consecutive days.Serum creatinine(SCr),blood urea nitrogen(BUN),24 h urinary protein(24 h MTP)and glomerular filtration rate(eGFR)were measured by biochemical method;renal histopathological changes were observed by hematoxylin-eosin(HE)staining.Renal collagen deposition in rats was observed by Masson staining.[Results]The SCr in model group and the high,medium and low dose experimental groups were(340.00±22.99),(176.80±18.60),(234.75±13.59),(266.11±14.78)μmol/L,and BUN were(23.74±2.51),(14.53±2.25),(18.78±0.88),(18.90±2.14)mmol/L;24 h MTP were(675.86±74.58),(323.81±41.83),(438.84±34.69),(493.76±37.04)mg/d;eGFR were(19.30±2.48),(49.96±10.95),(32.61±10.75),(27.18±5.98)mL/min,and the difference was statistically significant compared with the normal group(all P<0.05).HE staining and Masson staining showed that compared with normal group,the renal interstitial lesions in model group were severe and the renal interstitial collagen material was deposited in a large amount.The renal interstitial tubule injury was relieved and the renal interstitial collagen deposition was reduced in experimental groups.And the difference was statistically significant(all P<0.01).[Conclusions]Manshenkangning can significantly protect the kidney against the progress of interstitial fibrosis in rats.Its possible mechanism is to regulate the activity of SIRT1 and inhibit the expression of COX-2 in order to resist the inflammatory reaction of kidney and improve the ability of anti-oxidative stress of kidney,thus delaying the occurrence and development of chronic renal failure.

Early detection of colorectal cancer based on circular DNA and common clinical detection indicators

BACKGROUND Colorectal cancer(CRC) is the third most common cancer worldwide, and it is the second leading cause of death from cancer in the world, accounting for approximately 9% of all cancer deaths. Early detection of CRC is urgently needed in clinical practice.AIM To build a multi-parameter diagnostic model for early detection of CRC.METHODS Total 59 colorectal polyps(CRP) groups, and 101 CRC patients(38 early-stage CRC and 63 advanced CRC) for model establishment. In addition, 30 CRP groups,and 62 CRC patients(30 early-stage CRC and 32 advanced CRC) were separately included to validate the model. 51 commonly used clinical detection indicators and the 4 extrachromosomal circular DNA markers NDUFB7, CAMK1D, PIK3CD and PSEN2 that we screened earlier. Four multi-parameter joint analysis methods:binary logistic regression analysis, discriminant analysis, classification tree and neural network to establish a multi-parameter joint diagnosis model.RESULTS Neural network included carcinoembryonic antigen(CEA), ischemia-modified albumin(IMA),sialic acid(SA), PIK3CD and lipoprotein a(LPa) was chosen as the optimal multi-parameter combined auxiliary diagnosis model to distinguish CRP and CRC group, when it differentiated 59CRP and 101 CRC, its overall accuracy was 90.8%, its area under the curve(AUC) was 0.959(0.934,0.985), and the sensitivity and specificity were 91.5% and 82.2%, respectively. After validation,when distinguishing based on 30 CRP and 62 CRC patients, the AUC was 0.965(0.930-1.000), and its sensitivity and specificity were 66.1% and 70.0%. When distinguishing based on 30 CRP and 32early-stage CRC patients, the AUC was 0.960(0.916-1.000), with a sensitivity and specificity of 87.5% and 90.0%, distinguishing based on 30 CRP and 30 advanced CRC patients, the AUC was 0.970(0.936-1.000), with a sensitivity and specificity of 96.7% and 86.7%.CONCLUSION We built a multi-parameter neural network diagnostic model included CEA, IMA, SA, PIK3CD and LPa for early detection of CRC, compared to the conventional CEA, it showed significant improvement.

Natural product rhynchophylline prevents stress-induced hair graying by preserving melanocyte stem cells via theβ2 adrenergic pathway suppression

Norepinephrine(NA),a stress hormone,can accelerate hair graying by binding toβ2 adrenergic receptors(β_(2)AR)on melanocyte stem cells(McSCs).From this,NA-β_(2)AR axis could be a potential target for preventing the stress effect.However,identifying selective blockers forβ_(2)AR has been a key challenge.Therefore,in this study,advanced computer-aided drug design(CADD)techniques were harnessed to screen natural molecules,leading to the discovery of rhynchophylline as a promising compound.Rhynchophylline exhibited strong and stable binding within the active site ofβ_(2)AR,as verified by molecular docking and dynamic simulation assays.When administered to cells,rhyncho-phylline effectively inhibited NA-β_(2)AR signaling.This intervention resulted in a significant reduction of hair graying in a stress-induced mouse model,from 28.5%to 8.2%.To gain a deeper understanding of the underlying mechanisms,transcriptome sequencing was employed,which revealed that NA might disrupt melanogenesis by affecting intracellular calcium balance and promoting cell apoptosis.Importantly,rhynchophylline acted as a potent inhibitor of these downstream pathways.In conclusion,the study demonstrated that rhynchophylline has the potential to mitigate the negative impact of NA on melanogenesis by targetingβ_(2)AR,thus offering a promising solution for preventing stress-induced hair graying.

Integration of scRNA-Seq and Bulk RNA-Seq to analyze the heterogeneity ofcolorectal cancer immune cells and establish a molecular risk model

Background:Colorectal cancer(CRC)is a highly heterogeneous malignant tumor that significantly impacts clinical diagnosis and treatment.Single-cell RNA sequencing is an innovative method for exploring tumor heterogeneity and understanding its role at cellular and genetic levels.Method:The colorectal cancer Single-cell RNA sequencing data were analysed on the immune.RNA-seq data in bulk form was utilized to assess the major genes of the immune cell subsets linked to CRC.We conducted an analysis of the abundance of immune cells in the microenvironment of CRC,and also performed weighted gene co-expression network analysis.Gene set enrichment analysis helped perform two analytical procedures of subtype groups.Furthermore,Least absolute shrinkage and selection operator regression was employed to analyse and screen for a gene signature.Finally,quantitative PCR Was performed to detect the expression levels of signature genes in CRC.Results:The Single-cell RNA sequencing(GSE146771)dataset was integrated to obtain 9 cell clusters.The Single-sample gene set enrichment analysis showed that the related gene expression of T-cell subsets of different functional statuses could vary greatly between patients with GSE146771.Immune cell analysis of TCGA-CRC indicated an improved overall survival rate for patients with elevated Th2 cell abundance.Five-gene signature(Risk Score=-0.205×CDC25C-0.231×GSTCD-0.010×KPNA2-0.002×KIF15-0.171×ORC1)was developed by weighted correlation network analysis,and lasso Cox regression.Then,the risk prediction efficacy of the signature was validated in four GSE datasets.Furthermore,the expression of five genes was reduced in CRC tissue by quantitative PCR.Conclusion:Five-gene signature based on CRC heterogeneity was developed as a prognosis predictor,which can serve as a potential treatment target.