Several clinical trials have demonstrated the potent antiviral efficacy of entecavir (ETV), and this relatively new nucleoside analogue drug has rapidly become a frequently prescribed therapy for chronic hepatitis B (...Several clinical trials have demonstrated the potent antiviral efficacy of entecavir (ETV), and this relatively new nucleoside analogue drug has rapidly become a frequently prescribed therapy for chronic hepatitis B (CHB) worldwide. While the studies have also shown a good overall safety profile for ETV, adverse drug reactions (ADRs) in patients with advanced cirrhosis have been reported and represent a broad spectrum of drug-induced injuries, including lactic acidosis, myalgia, neuropathy, azotemia, hypophosphatemia, muscular weakness, and pancreatitis, as well as immune-mediated responses (i.e., allergic reactions). Cutaneous ADRs associated with ETV are very rare, with only two case reports in the publicly available literature; both of these cases were classified as unspecified hypersensitivity allergic (type I) ADR, but neither were reported as pathologically proven or as evaluated by cytokine release analysis. Here, we report the case of a 45-year-old woman who presented with a generalized maculopapular rash after one week of ETV treatment for lamivudine-resistant CHB. The patient reported having experienced a similar skin eruption during a previous three-month regimen of ETV, for which she had self-discontinued the medication. Histopathological analysis of a skin biopsy showed acanthotic epidermis with focal parakeratosis and a perivascular lymphocytic infiltrate admixed with interstitial eosinophils in the papillary and reticular dermis, consistent with a diagnosis of drug sensitivity. A lymphocyte stimulation test showed significantly enhanced IL-4, indicating a classification of type IVb delayed hypersensitivity. The patient was switched to an adefovir-lamivudine combination regimen and the skin eruption resolved two weeks after the ETV withdrawal. This case represents the first pathologically and immunologically evidenced ETV-induced delayed type hypersensitivity skin reaction reported to date. Physicians should be aware of the potential, although rare, for cutaneous ADRs associated with ETV treatment.展开更多
It is well documented that dietary restriction can prevent many different diseases and extend the life spans of different rodent species. In the previous study, we reported that intermittent fasting (IF) as well as mo...It is well documented that dietary restriction can prevent many different diseases and extend the life spans of different rodent species. In the previous study, we reported that intermittent fasting (IF) as well as moderate dietary restriction ameliorated the allergic dermatitis in ICR mice. In the present study, we demonstrated the ameliorative effects of IF on allergic dermatitis in NC/Nga mice, a strain known as a model for atopic dermatitis. Interestingly, the total number of CD4+CD8+ double positive thymocyte in mice after IF significantly decreased in comparison to that in mice fed ad libitum. Although it was reported that an immunosuppressive compound inhibited the contact allergic response by inducing the CD4+CD25+ regulatory T-cells, IF did not affect regulatory T cells in the present study. These results suggested that CD4+CD8+ double positive thymocytes play an important role in the regulation of allergy by IF in NC/Nga mice.展开更多
Objective: To study the function of ce ll ular immunity in patients with hyper-IgE syndrome (HIE). Methods: T-lymphocyte subtypes of the peripheral blood and cutaneous delayed-typ e hypersensitivity (DTH) response ...Objective: To study the function of ce ll ular immunity in patients with hyper-IgE syndrome (HIE). Methods: T-lymphocyte subtypes of the peripheral blood and cutaneous delayed-typ e hypersensitivity (DTH) response to two recall antigens, tetanus toxoid (TT) an d purified protein derivative(PPD), were measured in five patients with HIE and 15 healthy controls, respectively. Results: The CD4+ cell cou nts in HIE group were significantly lower than those in control group (P<0. 01). In contrast, CD8+ cells were significantly higher than those in the contro l (P<0.01). The induration sizes of DTH response to two recall antigens wer e smaller in HIE group than those in the control group (P<0.01). Co nclusion: There was an immunologic dysfunction of T lymphocytes in the p atients with HIE.展开更多
The tuberculin Purified Protein Derivative (PPD) skin test is widely used;however, the results are often inaccurate. Positive results can be observed in patients with active tuberculosis (TB) as well as in BCG-vaccina...The tuberculin Purified Protein Derivative (PPD) skin test is widely used;however, the results are often inaccurate. Positive results can be observed in patients with active tuberculosis (TB) as well as in BCG-vaccinated persons and individuals who are infected with mycobacteria but have not developed the disease. MPT64, an antigen secreted from actively growing Mycobacterium tuberculosis and some strains of M. bovis BCG such as BCG Tokyo and BCG Russia, is immunogenic and elicits delayed-type hypersensitivity (DTH) in guinea pigs and humans. This antigen has been used to develop a new skin test for the diagnosis of active TB infection. Two of the antigens encoded by the M. tuberculosis-specific region of difference 1 (RD1, deleted in M. bovis BCG strains), CFP10 (culture filtrate protein 10) and ESAT6 (early secreted antigenic target-6), also induce M. tuberculosis-specific DTH responses. The aim of this study was to investigate the DTH responses in guinea pigs infected with M. tuberculosis or M. bovis BCG Tokyo elicited by three purified recombinant proteins (rMPT64, rCFP10 and rESAT6) compared to those elicited by PPD. In this study genes encoding MPT64, CFP10, and ESAT6 were cloned and expressed as recombinant proteins with the addition of a C-terminal His6 tag for ease of purification by Immobilized Metal ion Affinity Chromatography (IMAC). The recombinant proteins (rMPT64, rCFP10, and rESAT6) were purified to homogeneity and were used to elicit DTH responses in guinea pigs infected with M. tuberculosis or M. bovis BCG Tokyo. The results showed that rMPT64 elicits a DTH response comparable to that of PPD in M. bovis BCG Tokyo-vaccinated animals. However, M. tuberculosis-infected animals show less reactivity to rMPT64 than they do to PPD. Although single rCFP10 or rESAT6 did not readily elicit a DTH response in M. tuberculosis-infected animals, combining these antigens with rMPT64 led to an increased DTH response, thus enabling the detection of TB infection.展开更多
Dear Editor,The tuberculin skin test(TST)reagents have continuously improved,with the ESAT6-CFP10(EC)test having recently been introduced,but are seldom based on the direction of the delayed-type hypersensitivity(DTH)...Dear Editor,The tuberculin skin test(TST)reagents have continuously improved,with the ESAT6-CFP10(EC)test having recently been introduced,but are seldom based on the direction of the delayed-type hypersensitivity(DTH)mechanism.Previous studies only partially showed the infiltration and activation of immune cells and the production of cytokines of the skin induration[1,2],and lack the detailed measurements of cell proportions and gene expression in the DTH response.Therefore,in this study,we revealed the comprehensive characteristics of DTH by single-cell RNA sequencing(scRNA-seq)in the guinea pig tuberculosis(TB)model[Experimental Animal Welfare Ethics Committee,Beijing Tuberculosis and Thoracic Tumor Research Institute(2021-064)].展开更多
Delayed wound healing following radical gastrectomy remains an important yet underappreciated complication that prolongs hospitalization,increases costs,and undermines patient recovery.In An et al’s recent study,the ...Delayed wound healing following radical gastrectomy remains an important yet underappreciated complication that prolongs hospitalization,increases costs,and undermines patient recovery.In An et al’s recent study,the authors present a machine learning-based risk prediction approach using routinely available clinical and laboratory parameters.Among the evaluated algorithms,a decision tree model demonstrated excellent discrimination,achieving an area under the curve of 0.951 in the validation set and notably identifying all true cases of delayed wound healing at the Youden index threshold.The inclusion of variables such as drainage duration,preoperative white blood cell and neutrophil counts,alongside age and sex,highlights the pragmatic appeal of the model for early postoperative monitoring.Nevertheless,several aspects warrant critical reflection,including the reliance on a postoperative variable(drainage duration),internal validation only,and certain reporting inconsistencies.This letter underscores both the promise and the limitations of adopting interpretable machine learning models in perioperative care.We advocate for transparent reporting,external validation,and careful consideration of clinically actionable timepoints before integration into practice.Ultimately,this work represents a valuable step toward precision risk stratification in gastric cancer surgery,and sets the stage for multicenter,prospective evaluations.展开更多
A Langevin delayed fractional system with multiple delays in control,is a delayed fractional system that includes delay parameters in both state and control,is first introduced.This paper is devoted to investigating t...A Langevin delayed fractional system with multiple delays in control,is a delayed fractional system that includes delay parameters in both state and control,is first introduced.This paper is devoted to investigating the relative controllability of the Langevin delayed fractional system with multiple delays in control.For linear systems to be relatively controllable,necessary and sufficient circumstances are identified by introducing and employing the Gramian matrix.The sufficient conditions for the relative controllability of semilinear systems are ofered based on Schauder's fixed point theorem.As an unusual approach,the controllability results of the delayed system are built for the first time on the exact solution produced by the MittagLeffler type function although controllability ones in the literature are built on the Volterra integral equations or the mild solutions produced by resolvent families.展开更多
OBJECTIVE:To explore if Hewei Jiangni granule(和胃降逆颗粒,HWJNG)could regulate esophageal hypersensitivity via stromal interaction molecule 1(STIM1)/transient receptor potential vanilloid subfamily member 1(TRPV1)pat...OBJECTIVE:To explore if Hewei Jiangni granule(和胃降逆颗粒,HWJNG)could regulate esophageal hypersensitivity via stromal interaction molecule 1(STIM1)/transient receptor potential vanilloid subfamily member 1(TRPV1)pathway.METHODS:Qualitative analysis of HWJNG was analysis by high performance of liquid and gas chromatography.In vivo,animal model of non-erosive reflux disease(NERD)was established by fructose intake and restraint stress.HWJNG and Omeprazole were administered by gavage to the drug intervention group.Reflux and visceral hypersensitivity were analyzed by pathological changes,PH value test,mechanical paw withdrawal threshold,thermal withdrawal latency and mast cells(MCs)degranulation.In vitro,substance P(SP)-induced P815 cells and dorsal root ganglion(DRG)cells were cocultured.Expression in both mice and cells of STIM1,TRPV1,and esophageal visceral hypersensitivity-related gastrointestinal neurochemicals were validated by enzyme linked immunosorbent assays,quantitative realtime polymerase chain reaction(qRT-PCR)and Western blot.Moreover,overexpression and small interfering RNA against STIM1 were utilized to verify of the role of HWJNG in DRG cells.RESULTS:HWJNG significantly suppressed intercellular space widening,injury of mitochondrial,MCs degranulation,mechanical allodynia and heat neuropathic sensory and increased pH value of esophageal mucosa in NERD mice.HWJNG inhibited expression of visceral hypersensitivityrelated gastrointestinal neurochemicals in esophageal mucosa and activated P815 cells,and expression of the STIM1,TRPV1 and related neurotransmitters in DRG and DRG cells.STIM1 siRNA and HWJNG both reduced P815 cells adhesion to DRGs cells and Ca2+flow into the cytoplasmic space of DRG cells.Furthermore,HWJNG could reversed STIM1 overexpression induced upregulation of TRPV1.CONCLUSION:HWJNG suppressed intercellular space widening in NERD mice,stabilized MCs and restored neuronal hyperexcitability by regulating visceral hypersensitivity via STIM1/TRPV1 pathway.展开更多
Objective:The neurotoxicity of carbon monoxide(CO)to the central nervous system is a key pathogenesis of delayed encephalopathy after acute carbon monoxide poisoning(DEACMP).Our previous study found that retinoic acid...Objective:The neurotoxicity of carbon monoxide(CO)to the central nervous system is a key pathogenesis of delayed encephalopathy after acute carbon monoxide poisoning(DEACMP).Our previous study found that retinoic acid(RA)can suppress the neurotoxic effects of CO.This study further explores,in vivo and in vitro,the molecular mechanisms by which RA alleviates CO-induced central nervous system damage.Methods:A cytotoxic model was established using the mouse hippocampal neuronal cell line HT22 and primary oligodendrocytes exposed to CO,and a DEACMP animal model was established in adult Kunming mice.Cell viability and apoptosis of hippocampal neurons and oligodendrocytes were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay and Annexin V/propidium iodide(PI)double staining.The transcriptional and protein expression of each gene was detected using real time fluorescence quantitative PCR(RT-qPCR)and Western blotting.Long noncoding RNA(lncRNA)SNHG15 and LINGO-1 were knocked down or overexpressed to observe changes in neurons and oligodendrocytes.In DEACMP mice,SNHG15 or LINGO-1 were knocked down to assess changes in central nervous tissue and downstream protein expression.Results:RA at 10 and 20μmol/L significantly reversed CO-induced apoptosis of hippocampal neurons and oligodendrocytes,downregulation of SNHG15 and LINGO-1,and upregulation of brain-derived neurotrophic factor(BDNF)and tyrosine kinase receptor B(TrkB)(all P<0.05).Overexpression of SNHG15 or LINGO-1 weakened the protective effect of RA against CO-induced cytotoxicity(all P<0.05).Knockdown of SNHG15 or LINGO-1 alleviated CO-induced apoptosis of hippocampal neurons and oligodendrocytes and upregulated BDNF and TrkB expression levels(all P<0.05).Experiments in DEACMP model mice showed that knockdown of SNHG15 or LINGO-1 mitigated central nervous system injury in DEACMP(all P<0.05).Conclusion:RA alleviates CO-induced apoptosis of hippocampal neurons and oligodendrocytes,thereby reducing central nervous system injury and exerting neuroprotective effects.LncRNA SNHG15 and LINGO-1 are key molecules mediating RA induced inhibition of neuronal apoptosis and are associated with the BDNF/TrkB pathway.These findings provide a theoretical framework for optimizing the clinical treatment of DEACMP and lay an experimental foundation for elucidating its molecular mechanisms.展开更多
Drug hypersensitivity reactions(DHRs),which produce symptoms from skin rash to anaphylaxis,are immune-mediated adverse reactions caused by drug formulations.The diagnosis of DHRs is challenging due to the lack of stan...Drug hypersensitivity reactions(DHRs),which produce symptoms from skin rash to anaphylaxis,are immune-mediated adverse reactions caused by drug formulations.The diagnosis of DHRs is challenging due to the lack of standardization for many drugs,and both underdiagnosis and overdiagnosis hamper the follow-up treatment of patients.Therefore,improved methods for diagnosing patients with suspected DHRs are needed.In this review,we analyzed traditional methods used to diagnose DHRs as well as new diagnostic advances made during the last 2 years.None of the diagnostic methods is perfect,as each exhibits varying sensitivities to different types of DHRs.Overall,our analysis indicates that the accuracy of DHR diagnosis can be improved by obtaining a detailed clinical history,physical examination,in vivo and in vitro testing.展开更多
BACKGROUND Reflux hypersensitivity(RH)constitutes roughly 14%of patients with heartburn and 34%of those with refractory heartburn,yet it is inadequately comprehended.AIM To investigate the clinical characteristics and...BACKGROUND Reflux hypersensitivity(RH)constitutes roughly 14%of patients with heartburn and 34%of those with refractory heartburn,yet it is inadequately comprehended.AIM To investigate the clinical characteristics and risk factors associated with RH.METHODS We conducted a retrospective analysis of 109 patients with RH and 384 healthy controls from three medical centers between January 2022 and December 2023.Comprehensive data encompassing symptoms,motility,impedance-pH monitoring,and psychological evaluations were collected.RESULTS RH patients encountered a greater frequency of weakly acidic reflux(WAR)events compared to acidic reflux or nonacidic reflux(NAR)events.Upright reflux time(1.22%)exceeds supine reflux time(0.54%)(P<0.05).Extraesophageal symptoms were more prevalent among younger patients and those with elevated NAR(P<0.05).The acidic reflux,WAR,NAR,and peristaltic contraction break length in male patients exceeded those in female patients(P<0.05).Age[odds ratio(OR)=5.633],hiatal hernia(OR=13.103),and anxiety(OR=17.342)constituted independent risk factors for RH.CONCLUSION WAR and NAR are pivotal in RH.Patients with increased NAR are more likely to experience extraesophageal symptoms.Age,hiatal hernia,and anxiety are significant independent risk factors for RH.展开更多
OBJECTIVE:this study to investigate the mechanism underlying the electroacupuncture(EA)alleviates colorectal hypersensitivity,a feature of irritable bowel syndrome(IBS).METHODS:The colorectal hypersensitivity model wa...OBJECTIVE:this study to investigate the mechanism underlying the electroacupuncture(EA)alleviates colorectal hypersensitivity,a feature of irritable bowel syndrome(IBS).METHODS:The colorectal hypersensitivity model was established by treating mice with zymosan.Electrophysiological techniques,Western blotting and immunofluorescence staining were used to detect the changes of the sensitive state of the colorectum and the response in spinal ganglion and spinal cord after acupuncture intervention.RESULTS:colorectal distension studies revealed that repetitive applied electroacupuncture treatment on mice could significant alleviates colorectal intensity.Western blotting studies with nerve growth factor(NGF)in the colorectum,substance P(SP)in the spinal ganglion,protein kinase C gamma(PKCγ)in the spinal cord,and transient receptor potential vanilloid 1(TRPV1)showed that electroacupuncture suppressed zymosan-induced expression of TRPV1,NGF and SP in multiple tissues.Immunofluorescence labeling results showed that EA attenuated the expression of NGF in the colorectum,SP in the spinal ganglion,PKCγin the spinal cord,and TRPV1 in all three tissues in zymosan-treated mice.Moreover,the number of neurons double-positive for TRPV1/Isolectin B4(IB4)and TRPV1/Neurofilament(NF)200 was increased in the spinal ganglion.CONCLUSION:these results provide molecular-level evidence that EA alleviates zymosan-induced colorectal hypersensitivity by altering the expression of pain-associated proteins in the colorectum and spinal cord.EA has a potential to be therapeutic intervention option for IBS treatment.展开更多
Through systematic analysis of risk factors associated with postoperative delayed discharge following retrograde intrarenal surgery(RIRS)with flexible ureteroscopic holmium laser lithotripsy under ambulatory surgery p...Through systematic analysis of risk factors associated with postoperative delayed discharge following retrograde intrarenal surgery(RIRS)with flexible ureteroscopic holmium laser lithotripsy under ambulatory surgery protocols,this study aims to develop and validate a risk prediction model for discharge delay.The ultimate objectives include establishing evidence-based clinical guidelines for urolithiasis management,enabling proactive intervention strategies,and optimizing physician-patient communication efficiency.METHODS:This retrospective cohort study analyzed clinical data from 253 patients undergoing ambulatory retrograde intrarenal surgery(RIRS)with flexible ureteroscopic holmium laser lithotripsy at the Day Surgery Unit and Urology Department of Hunan Provincial People's Hospital between January 2023 and December 2024.To identify predictors of discharge delay,Lasso-regularized logistic regression analysis was implemented for variable selection,followed by multivariable logistic regression modeling via R statistical software(version 4.3.1).A clinical prediction nomogram was developed to visualize risk stratification,with model performance evaluated through receiver operating characteristic(ROC)curve analysis,calibration plots,and decision curve analysis(DCA).Internal validation was conducted using 1,000-cycle bootstrap resampling to ensure model generalizability.展开更多
This paper is concerned with design-ing symbol labeling for a low-density parity-check(LDPC)-coded delayed bit-interleaved coded modu-lation(DBICM)scheme in a two-way relay channel(TWRC).We first present some properti...This paper is concerned with design-ing symbol labeling for a low-density parity-check(LDPC)-coded delayed bit-interleaved coded modu-lation(DBICM)scheme in a two-way relay channel(TWRC).We first present some properties of symbol labeling within a phase shift keying(PSK)modula-tion.These properties reduce the candidate labeling search space.Based on this search space,we take DBICM capacity as the cost function and propose a general method for optimizing symbol labeling by em-ploying the differential evolution algorithm.Numeri-cal results show that our labeling obtains a signal-to-noise ratio(SNR)gain up to 0.45 dB with respect to Gray labeling.展开更多
Irritable bowel syndrome-diarrhea(IBS-D)is a prevalent functional bowel disease severely impairs the quality of life of patients.Visceral hypersensitivity(VH)is the main symptom of IBS-D.Probiotics have been found to ...Irritable bowel syndrome-diarrhea(IBS-D)is a prevalent functional bowel disease severely impairs the quality of life of patients.Visceral hypersensitivity(VH)is the main symptom of IBS-D.Probiotics have been found to effectively alleviate VH.In this study,neonatal maternal separation(NMS)was used to induce VH in 72 rats and investigated the effects of daily gavage of 3×10^(9) CFU of Lactobacillus and Bifidobacterium on alleviating the symptoms of IBS-D and behavioral interventions,as well as exploring potential mechanisms.The results demonstrated that L.acidophilus and B.breve could alleviate the symptoms of IBS-D such as VH and increased frequency of bowel movements,as well as improving non-spatial memory in NMS rats.These effects were achieved by modulating the composition of gut microbiota and metabolites(including short-chain fatty acids,deoxycholic acid and adenosine),and by regulating the expression of genes and proteins associated with the NGF/TrkA signaling pathway,tryptophan metabolism,and inflammatory factors in the hippocampus.This finding suggests that L.acidophilus and B.breve have promising potential for the alleviation of IBS.展开更多
BACKGROUND Delayed post-pancreatectomy hemorrhage(PPH)is life-threatening,and endovascular interventions show promise.This retrospective study aimed to evaluate endovascular treatment outcomes for delayed PPH and iden...BACKGROUND Delayed post-pancreatectomy hemorrhage(PPH)is life-threatening,and endovascular interventions show promise.This retrospective study aimed to evaluate endovascular treatment outcomes for delayed PPH and identify mortality risk factors.AIM To conduct a single-center retrospective study of 88 patients with delayed PPH to systematically evaluate the clinical efficacy of endovascular treatment,identify independent risk factors for six-month mortality,and propose and validate a predictive model for individualized management of high-risk patients.METHODS This retrospective analysis included 88 patients with delayed PPH treated by endovascular intervention.Patients were stratified into survival(n=64)and mortality(n=24)groups.Clinical and procedural variables were assessed using univariate and multivariate logistic regression.Significant predictors were incorporated into a prognostic nomogram.Model performance was assessed through discrimination(area under the receiver operating characteristic curve),calibration,and decision curve analysis.RESULTS Technical and clinical success rates were 92.0%and 60.2%,respectively.The overall six-month mortality rate was 27.3%(24/88).Independent predictors of mortality included advanced age,prolonged operative time,shorter hospital stay,intra-abdominal infection,coagulation dysfunction,common hepatic artery bleeding,and failure to achieve clinical success.The nomogram demonstrated excellent discrimination(area under the receiver operating characteristic curve=0.943),with good calibration and favorable net benefit on decision curve analysis.CONCLUSION We proposed and validated a predictive nomogram for six-month mortality following endovascular treatment for delayed PPH.The model facilitates individualized risk stratification and may guide clinical decision-making.Early identification of high-risk patients-particularly older individuals or those with infection or coagulopathy-and prompt,personalized intervention may improve outcomes in this high-risk population.展开更多
[Objectives]To explore the mechanism of action of Tongxieyaofang ultrafine granular powder in treating visceral hypersensitivity in rats with diarrhea-predominant irritable bowel syndrome(IBS-D)based on enteric glial ...[Objectives]To explore the mechanism of action of Tongxieyaofang ultrafine granular powder in treating visceral hypersensitivity in rats with diarrhea-predominant irritable bowel syndrome(IBS-D)based on enteric glial cells(EGCs).[Methods]Eighty-four healthy male Wistar rats of SPF grade were selected and randomly assigned to seven groups,each comprising 12 rats:a normal control group,a model control group,a traditional Tongxieyaofang granular powder group(4.060 g/kg),three Tongxieyaofang ultrafine granular powder groups at low,medium,and high doses(1.015,2.030,and 4.060 g/kg of raw drug,respectively),and a pinaverium bromide group(0.018 g/kg).With the exception of the normal control group,all other groups were subjected to an IBS-D visceral hypersensitivity sensitivity model in rats developed by the chronic water avoidance stress method.Three days post modeling,the rats received continuous oral gavage administration for 8 d.Following the treatment period,serum and colon tissue samples were collected from each group.The BDNF level in the serum was quantified using ELISA.Additionally,the protein expression levels of GFAP,BDNF,and TrkB in colon tissues were assessed via Western blot assay.[Results]Compared to the normal control group,the serum BDNF levels in the model control group were significantly elevated(P<0.01).In contrast,each treatment group exhibited a significant reduction in serum BDNF levels relative to the model control group(P<0.01).Furthermore,the protein expression levels of GFAP,BDNF,and TrkB in colon tissue were significantly higher in the model control group compared to the normal control group(P<0.05,P<0.01).Conversely,these protein expressions were significantly decreased in each treatment group compared to the model control group(P<0.05,P<0.01).[Conclusions]Tongxieyaofang ultrafine granular powder effectively alleviates visceral sensitivity in IBS-D rats and inhibits the activation of EGCs,speculating that its mechanism of action involves the suppression of abnormal EGC activation.展开更多
Background:Contrast-enhanced magnetic resonance neurography(ceMRN)can enhance brachial plexus visualization and quality of imaging.However,the interval between contrast injection and scanning that provides the highest...Background:Contrast-enhanced magnetic resonance neurography(ceMRN)can enhance brachial plexus visualization and quality of imaging.However,the interval between contrast injection and scanning that provides the highest-quality images is not known.Methods:Fifteen patients underwent brachial plexus imaging using the 3D T2-NerveView sequence with a scanning duration of 5 min.A consecutive six-phase scan was initiated immediately at the start of contrast agent injection.Subsequently,all patients'images were classified into six groups according to the phases:group A(phase 1,delay 0 min),group B(phase 2,delay 5 min),group C(phase 3,delay 10 min),group D(phase 4,delay 15 min),group E(phase 5,delay 20 min),and group F(phase 6,delay 25 min).The image quality in each group was assessed based on nerve signal(signalnerve),muscle signal(signalmuscle),lymph node signal(signallymph node),background noise(BN),signal-to-noise ratio(SNR),contrast-to-noise ratio(CNR),and subjective score.Results:Signalnerve,signalmuscle,BN,and SNR did not significantly differ among the six groups(p>0.05).However,significant differences(p<0.05)were observed in signallymph node(F=16.067),CNR(F=9.495),and subjective score(χ^(2)=23.586).As the scanning delay increased,signallymph node intensity gradually increased whereas the CNR gradually decreased.The subjective score was significantly higher in groups B(4.830.24),C(4.900.21),D(4.870.30),E(4.830.31),and F(4.830.31)than in group A(4.470.30).Conclusion:We recommend performing brachial plexus ceMRN 5 min after contrast injection.With this delay,the brachial plexus can be visualized optimally with minimal interference from background signals.展开更多
Hydrogels are widely used in reservoir flow control to enhanced oil recovery.However,challenges such as environmental contamination from conventional crosslinkers,poor solubility of crosslinking agents,and short gelat...Hydrogels are widely used in reservoir flow control to enhanced oil recovery.However,challenges such as environmental contamination from conventional crosslinkers,poor solubility of crosslinking agents,and short gelation times under high-temperature conditions(e.g.,150℃)have hindered their practical application.Herein,we present the synthesis of amine-functionalized carbon quantum dots(NH_(2)-CQDs),which act as both a nano-crosslinker and a nano-reinforcing agent within hydrogel systems.The NH_(2)-CQDs-incorporated hydrogel can remain stability for 300 days under the conditions of a mineralization degree of 2.11×10^(4)mg/mL and 170℃,and has high tensile strength(371 kPa),good toughness(49.6 kJ/m~3),excellent viscoelasticity(G'=960 Pa,G"=460 Pa)and shear resistance.In addition,NH_(2)-CQDs adds many hydroxyl groups to the hydrogel,which can be attached to the surface of various substances.At the same time,micro-nano capsules containing NH_(2)-CQDs were formed by self-assembly of hydrophobic SiO_(2)on water droplets,the NH_(2)-CQDs solution is encapsulated in a capsule,and when stimulated by external conditions(temperature,pH,surfactant),the capsule releases the NH_(2)-CQDs solution,this method greatly delays the crosslinking time between polymer and crosslinker at high temperature.Under the condition of 170℃and pH=7,the gelation time of 10%hydrophobic SiO_(2)coated hydrogel is 44 times that of uncoated hydrogel,which can be effectively used for deep formation flow control,and CQD give hydrogels fluorescence properties that can be used for underground signal tracking.展开更多
BACKGROUND Visceral hypersensitivity is the core pathogenesis of irritable bowel syndrome(IBS)and is often accompanied by negative emotions such as anxiety or depression.Paraventricular hypothalamic nucleus(PVN)cortic...BACKGROUND Visceral hypersensitivity is the core pathogenesis of irritable bowel syndrome(IBS)and is often accompanied by negative emotions such as anxiety or depression.Paraventricular hypothalamic nucleus(PVN)corticotropin-releasing factor(CRF)is involved in the stress-related gastrointestinal dysfunction.Electroacupuncture(EA)has unique advantages for the treatment of visceral hypersensitivity and negative emotions in IBS patients.However,the underlying mechanisms remain unclear.AIM To investigate the pathological mechanisms visceral hypersensitivity and negative emotions in IBS,as well as the effect mechanism of EA.METHODS A model of diarrhoeal IBS(IBS-D)with negative emotions was prepared by chronic restraint combined with glacial acetic acid enema.The effect of EA was verified by abdominal withdrawal reflex and open-field test.PVN CRFcolonic mast cell(MC)/transient potential receptor vanilloid type 1(TRPV1)pathway was detected by immunofluorescence,Western blot,ELISA,and toluidine blue staining.Moreover,PVN CRFergic neurons were activated or inhibited by chemogenetical technique to observe the changes of effect indicator.RESULTS In the model group,IBS-D symptoms and negative emotions were successfully induced.Notably,the combination of Baihui(GV20)with Tianshu(ST25)and Dachangshu(BL25)acupoints showed the greatest efficacy in improving the negative emotions and visceral hypersensitivity in model mice.Furthermore,we found that EA inhibited overactivated PVN CRFergic neurons and the overexpression of serum CRF,colonic CRF,CRF-receptor 1(CRFR1),mast cell tryptase(MCT),protease-activated receptor 2 and TRPV1 in model mice.Moreover,we found that activating PVN CRFergic neurons induced negative emotions and visceral hypersensitivity in normal mice;however,inhibiting PVN CRFergic neurons alleviated negative emotions and intestinal symptoms in model mice and decreased the expression of colonic CRF-R1,MCT,and TRPV1.CONCLUSION This research highlights the key role of PVN CRF-MC CRF-R1 and the downstream MC/TRPV1 pathway in the pathological process of IBS-D and the mechanism of the effect of EA.展开更多
基金Supported by grant from the Chungbuk National University Hospital(2013)
文摘Several clinical trials have demonstrated the potent antiviral efficacy of entecavir (ETV), and this relatively new nucleoside analogue drug has rapidly become a frequently prescribed therapy for chronic hepatitis B (CHB) worldwide. While the studies have also shown a good overall safety profile for ETV, adverse drug reactions (ADRs) in patients with advanced cirrhosis have been reported and represent a broad spectrum of drug-induced injuries, including lactic acidosis, myalgia, neuropathy, azotemia, hypophosphatemia, muscular weakness, and pancreatitis, as well as immune-mediated responses (i.e., allergic reactions). Cutaneous ADRs associated with ETV are very rare, with only two case reports in the publicly available literature; both of these cases were classified as unspecified hypersensitivity allergic (type I) ADR, but neither were reported as pathologically proven or as evaluated by cytokine release analysis. Here, we report the case of a 45-year-old woman who presented with a generalized maculopapular rash after one week of ETV treatment for lamivudine-resistant CHB. The patient reported having experienced a similar skin eruption during a previous three-month regimen of ETV, for which she had self-discontinued the medication. Histopathological analysis of a skin biopsy showed acanthotic epidermis with focal parakeratosis and a perivascular lymphocytic infiltrate admixed with interstitial eosinophils in the papillary and reticular dermis, consistent with a diagnosis of drug sensitivity. A lymphocyte stimulation test showed significantly enhanced IL-4, indicating a classification of type IVb delayed hypersensitivity. The patient was switched to an adefovir-lamivudine combination regimen and the skin eruption resolved two weeks after the ETV withdrawal. This case represents the first pathologically and immunologically evidenced ETV-induced delayed type hypersensitivity skin reaction reported to date. Physicians should be aware of the potential, although rare, for cutaneous ADRs associated with ETV treatment.
文摘It is well documented that dietary restriction can prevent many different diseases and extend the life spans of different rodent species. In the previous study, we reported that intermittent fasting (IF) as well as moderate dietary restriction ameliorated the allergic dermatitis in ICR mice. In the present study, we demonstrated the ameliorative effects of IF on allergic dermatitis in NC/Nga mice, a strain known as a model for atopic dermatitis. Interestingly, the total number of CD4+CD8+ double positive thymocyte in mice after IF significantly decreased in comparison to that in mice fed ad libitum. Although it was reported that an immunosuppressive compound inhibited the contact allergic response by inducing the CD4+CD25+ regulatory T-cells, IF did not affect regulatory T cells in the present study. These results suggested that CD4+CD8+ double positive thymocytes play an important role in the regulation of allergy by IF in NC/Nga mice.
文摘Objective: To study the function of ce ll ular immunity in patients with hyper-IgE syndrome (HIE). Methods: T-lymphocyte subtypes of the peripheral blood and cutaneous delayed-typ e hypersensitivity (DTH) response to two recall antigens, tetanus toxoid (TT) an d purified protein derivative(PPD), were measured in five patients with HIE and 15 healthy controls, respectively. Results: The CD4+ cell cou nts in HIE group were significantly lower than those in control group (P<0. 01). In contrast, CD8+ cells were significantly higher than those in the contro l (P<0.01). The induration sizes of DTH response to two recall antigens wer e smaller in HIE group than those in the control group (P<0.01). Co nclusion: There was an immunologic dysfunction of T lymphocytes in the p atients with HIE.
文摘The tuberculin Purified Protein Derivative (PPD) skin test is widely used;however, the results are often inaccurate. Positive results can be observed in patients with active tuberculosis (TB) as well as in BCG-vaccinated persons and individuals who are infected with mycobacteria but have not developed the disease. MPT64, an antigen secreted from actively growing Mycobacterium tuberculosis and some strains of M. bovis BCG such as BCG Tokyo and BCG Russia, is immunogenic and elicits delayed-type hypersensitivity (DTH) in guinea pigs and humans. This antigen has been used to develop a new skin test for the diagnosis of active TB infection. Two of the antigens encoded by the M. tuberculosis-specific region of difference 1 (RD1, deleted in M. bovis BCG strains), CFP10 (culture filtrate protein 10) and ESAT6 (early secreted antigenic target-6), also induce M. tuberculosis-specific DTH responses. The aim of this study was to investigate the DTH responses in guinea pigs infected with M. tuberculosis or M. bovis BCG Tokyo elicited by three purified recombinant proteins (rMPT64, rCFP10 and rESAT6) compared to those elicited by PPD. In this study genes encoding MPT64, CFP10, and ESAT6 were cloned and expressed as recombinant proteins with the addition of a C-terminal His6 tag for ease of purification by Immobilized Metal ion Affinity Chromatography (IMAC). The recombinant proteins (rMPT64, rCFP10, and rESAT6) were purified to homogeneity and were used to elicit DTH responses in guinea pigs infected with M. tuberculosis or M. bovis BCG Tokyo. The results showed that rMPT64 elicits a DTH response comparable to that of PPD in M. bovis BCG Tokyo-vaccinated animals. However, M. tuberculosis-infected animals show less reactivity to rMPT64 than they do to PPD. Although single rCFP10 or rESAT6 did not readily elicit a DTH response in M. tuberculosis-infected animals, combining these antigens with rMPT64 led to an increased DTH response, thus enabling the detection of TB infection.
基金supported by the National Natural Science Foundation(81871691)the Beijing Municipal Natural Science Foundation(KZ202110025034).
文摘Dear Editor,The tuberculin skin test(TST)reagents have continuously improved,with the ESAT6-CFP10(EC)test having recently been introduced,but are seldom based on the direction of the delayed-type hypersensitivity(DTH)mechanism.Previous studies only partially showed the infiltration and activation of immune cells and the production of cytokines of the skin induration[1,2],and lack the detailed measurements of cell proportions and gene expression in the DTH response.Therefore,in this study,we revealed the comprehensive characteristics of DTH by single-cell RNA sequencing(scRNA-seq)in the guinea pig tuberculosis(TB)model[Experimental Animal Welfare Ethics Committee,Beijing Tuberculosis and Thoracic Tumor Research Institute(2021-064)].
文摘Delayed wound healing following radical gastrectomy remains an important yet underappreciated complication that prolongs hospitalization,increases costs,and undermines patient recovery.In An et al’s recent study,the authors present a machine learning-based risk prediction approach using routinely available clinical and laboratory parameters.Among the evaluated algorithms,a decision tree model demonstrated excellent discrimination,achieving an area under the curve of 0.951 in the validation set and notably identifying all true cases of delayed wound healing at the Youden index threshold.The inclusion of variables such as drainage duration,preoperative white blood cell and neutrophil counts,alongside age and sex,highlights the pragmatic appeal of the model for early postoperative monitoring.Nevertheless,several aspects warrant critical reflection,including the reliance on a postoperative variable(drainage duration),internal validation only,and certain reporting inconsistencies.This letter underscores both the promise and the limitations of adopting interpretable machine learning models in perioperative care.We advocate for transparent reporting,external validation,and careful consideration of clinically actionable timepoints before integration into practice.Ultimately,this work represents a valuable step toward precision risk stratification in gastric cancer surgery,and sets the stage for multicenter,prospective evaluations.
文摘A Langevin delayed fractional system with multiple delays in control,is a delayed fractional system that includes delay parameters in both state and control,is first introduced.This paper is devoted to investigating the relative controllability of the Langevin delayed fractional system with multiple delays in control.For linear systems to be relatively controllable,necessary and sufficient circumstances are identified by introducing and employing the Gramian matrix.The sufficient conditions for the relative controllability of semilinear systems are ofered based on Schauder's fixed point theorem.As an unusual approach,the controllability results of the delayed system are built for the first time on the exact solution produced by the MittagLeffler type function although controllability ones in the literature are built on the Volterra integral equations or the mild solutions produced by resolvent families.
基金National Natural Science Foundation of China:Study on the Molecular Mechanism of the Regulation of Crypt Goblet Cell Pyroptosis and Exocytosis to Repair Ulcerative Colitis Mucus Barrier by the Method of Clearing and Opening the Xuanfu from the Perspective of"Xuanfu-Crypt"(No.82305143),and National Natural Science Foundation of China:Exploring the Molecular Mechanism of"Hewei Jiangni Fang"Intervention in Non-erosive Reflux Disease Esophageal Hypersensitivity from the Perspective of Mas-related Gene X2/Stromal Interaction Molecule 1/Cell Adhesion Molecule 1 Pathway Regulation of Mast Cell/Dorsal Root Ganglion Communication based on the"Xinkai-Kujiang"Method(No.82374401)。
文摘OBJECTIVE:To explore if Hewei Jiangni granule(和胃降逆颗粒,HWJNG)could regulate esophageal hypersensitivity via stromal interaction molecule 1(STIM1)/transient receptor potential vanilloid subfamily member 1(TRPV1)pathway.METHODS:Qualitative analysis of HWJNG was analysis by high performance of liquid and gas chromatography.In vivo,animal model of non-erosive reflux disease(NERD)was established by fructose intake and restraint stress.HWJNG and Omeprazole were administered by gavage to the drug intervention group.Reflux and visceral hypersensitivity were analyzed by pathological changes,PH value test,mechanical paw withdrawal threshold,thermal withdrawal latency and mast cells(MCs)degranulation.In vitro,substance P(SP)-induced P815 cells and dorsal root ganglion(DRG)cells were cocultured.Expression in both mice and cells of STIM1,TRPV1,and esophageal visceral hypersensitivity-related gastrointestinal neurochemicals were validated by enzyme linked immunosorbent assays,quantitative realtime polymerase chain reaction(qRT-PCR)and Western blot.Moreover,overexpression and small interfering RNA against STIM1 were utilized to verify of the role of HWJNG in DRG cells.RESULTS:HWJNG significantly suppressed intercellular space widening,injury of mitochondrial,MCs degranulation,mechanical allodynia and heat neuropathic sensory and increased pH value of esophageal mucosa in NERD mice.HWJNG inhibited expression of visceral hypersensitivityrelated gastrointestinal neurochemicals in esophageal mucosa and activated P815 cells,and expression of the STIM1,TRPV1 and related neurotransmitters in DRG and DRG cells.STIM1 siRNA and HWJNG both reduced P815 cells adhesion to DRGs cells and Ca2+flow into the cytoplasmic space of DRG cells.Furthermore,HWJNG could reversed STIM1 overexpression induced upregulation of TRPV1.CONCLUSION:HWJNG suppressed intercellular space widening in NERD mice,stabilized MCs and restored neuronal hyperexcitability by regulating visceral hypersensitivity via STIM1/TRPV1 pathway.
基金supported by the Natural Science Foundation of Hunan Province(2021JJ31089)the Scientific Research Project of Health Commission of Hunan Province(202203104548),China。
文摘Objective:The neurotoxicity of carbon monoxide(CO)to the central nervous system is a key pathogenesis of delayed encephalopathy after acute carbon monoxide poisoning(DEACMP).Our previous study found that retinoic acid(RA)can suppress the neurotoxic effects of CO.This study further explores,in vivo and in vitro,the molecular mechanisms by which RA alleviates CO-induced central nervous system damage.Methods:A cytotoxic model was established using the mouse hippocampal neuronal cell line HT22 and primary oligodendrocytes exposed to CO,and a DEACMP animal model was established in adult Kunming mice.Cell viability and apoptosis of hippocampal neurons and oligodendrocytes were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay and Annexin V/propidium iodide(PI)double staining.The transcriptional and protein expression of each gene was detected using real time fluorescence quantitative PCR(RT-qPCR)and Western blotting.Long noncoding RNA(lncRNA)SNHG15 and LINGO-1 were knocked down or overexpressed to observe changes in neurons and oligodendrocytes.In DEACMP mice,SNHG15 or LINGO-1 were knocked down to assess changes in central nervous tissue and downstream protein expression.Results:RA at 10 and 20μmol/L significantly reversed CO-induced apoptosis of hippocampal neurons and oligodendrocytes,downregulation of SNHG15 and LINGO-1,and upregulation of brain-derived neurotrophic factor(BDNF)and tyrosine kinase receptor B(TrkB)(all P<0.05).Overexpression of SNHG15 or LINGO-1 weakened the protective effect of RA against CO-induced cytotoxicity(all P<0.05).Knockdown of SNHG15 or LINGO-1 alleviated CO-induced apoptosis of hippocampal neurons and oligodendrocytes and upregulated BDNF and TrkB expression levels(all P<0.05).Experiments in DEACMP model mice showed that knockdown of SNHG15 or LINGO-1 mitigated central nervous system injury in DEACMP(all P<0.05).Conclusion:RA alleviates CO-induced apoptosis of hippocampal neurons and oligodendrocytes,thereby reducing central nervous system injury and exerting neuroprotective effects.LncRNA SNHG15 and LINGO-1 are key molecules mediating RA induced inhibition of neuronal apoptosis and are associated with the BDNF/TrkB pathway.These findings provide a theoretical framework for optimizing the clinical treatment of DEACMP and lay an experimental foundation for elucidating its molecular mechanisms.
基金supported in part by grants from the Tianshan Innovation Team Fund Project of Xinjiang Uygur Autonomous Region(2023D14005)the General Project of the Natural Science Foundation of the Xinjiang Uygur Autonomous Region(2022D01A109).
文摘Drug hypersensitivity reactions(DHRs),which produce symptoms from skin rash to anaphylaxis,are immune-mediated adverse reactions caused by drug formulations.The diagnosis of DHRs is challenging due to the lack of standardization for many drugs,and both underdiagnosis and overdiagnosis hamper the follow-up treatment of patients.Therefore,improved methods for diagnosing patients with suspected DHRs are needed.In this review,we analyzed traditional methods used to diagnose DHRs as well as new diagnostic advances made during the last 2 years.None of the diagnostic methods is perfect,as each exhibits varying sensitivities to different types of DHRs.Overall,our analysis indicates that the accuracy of DHR diagnosis can be improved by obtaining a detailed clinical history,physical examination,in vivo and in vitro testing.
基金Supported by the Foundation of the Second Affiliated Hospital of Xi’an Jiaotong University,No.YJ(ZD)202301.
文摘BACKGROUND Reflux hypersensitivity(RH)constitutes roughly 14%of patients with heartburn and 34%of those with refractory heartburn,yet it is inadequately comprehended.AIM To investigate the clinical characteristics and risk factors associated with RH.METHODS We conducted a retrospective analysis of 109 patients with RH and 384 healthy controls from three medical centers between January 2022 and December 2023.Comprehensive data encompassing symptoms,motility,impedance-pH monitoring,and psychological evaluations were collected.RESULTS RH patients encountered a greater frequency of weakly acidic reflux(WAR)events compared to acidic reflux or nonacidic reflux(NAR)events.Upright reflux time(1.22%)exceeds supine reflux time(0.54%)(P<0.05).Extraesophageal symptoms were more prevalent among younger patients and those with elevated NAR(P<0.05).The acidic reflux,WAR,NAR,and peristaltic contraction break length in male patients exceeded those in female patients(P<0.05).Age[odds ratio(OR)=5.633],hiatal hernia(OR=13.103),and anxiety(OR=17.342)constituted independent risk factors for RH.CONCLUSION WAR and NAR are pivotal in RH.Patients with increased NAR are more likely to experience extraesophageal symptoms.Age,hiatal hernia,and anxiety are significant independent risk factors for RH.
基金the National Natural Science Foundation of China(No.81373724,Transient Potential Vanilloid Receptor1 Participates In The Mechanism Of Acupuncture Alleviating Visceral Hypersensitivity)the Joint Innovation Funds of China Academy of Chinese Medical Sciences(No.ZJYB2021-06,Clinical observation of acupuncture in the treatment of chronic urticaria)。
文摘OBJECTIVE:this study to investigate the mechanism underlying the electroacupuncture(EA)alleviates colorectal hypersensitivity,a feature of irritable bowel syndrome(IBS).METHODS:The colorectal hypersensitivity model was established by treating mice with zymosan.Electrophysiological techniques,Western blotting and immunofluorescence staining were used to detect the changes of the sensitive state of the colorectum and the response in spinal ganglion and spinal cord after acupuncture intervention.RESULTS:colorectal distension studies revealed that repetitive applied electroacupuncture treatment on mice could significant alleviates colorectal intensity.Western blotting studies with nerve growth factor(NGF)in the colorectum,substance P(SP)in the spinal ganglion,protein kinase C gamma(PKCγ)in the spinal cord,and transient receptor potential vanilloid 1(TRPV1)showed that electroacupuncture suppressed zymosan-induced expression of TRPV1,NGF and SP in multiple tissues.Immunofluorescence labeling results showed that EA attenuated the expression of NGF in the colorectum,SP in the spinal ganglion,PKCγin the spinal cord,and TRPV1 in all three tissues in zymosan-treated mice.Moreover,the number of neurons double-positive for TRPV1/Isolectin B4(IB4)and TRPV1/Neurofilament(NF)200 was increased in the spinal ganglion.CONCLUSION:these results provide molecular-level evidence that EA alleviates zymosan-induced colorectal hypersensitivity by altering the expression of pain-associated proteins in the colorectum and spinal cord.EA has a potential to be therapeutic intervention option for IBS treatment.
文摘Through systematic analysis of risk factors associated with postoperative delayed discharge following retrograde intrarenal surgery(RIRS)with flexible ureteroscopic holmium laser lithotripsy under ambulatory surgery protocols,this study aims to develop and validate a risk prediction model for discharge delay.The ultimate objectives include establishing evidence-based clinical guidelines for urolithiasis management,enabling proactive intervention strategies,and optimizing physician-patient communication efficiency.METHODS:This retrospective cohort study analyzed clinical data from 253 patients undergoing ambulatory retrograde intrarenal surgery(RIRS)with flexible ureteroscopic holmium laser lithotripsy at the Day Surgery Unit and Urology Department of Hunan Provincial People's Hospital between January 2023 and December 2024.To identify predictors of discharge delay,Lasso-regularized logistic regression analysis was implemented for variable selection,followed by multivariable logistic regression modeling via R statistical software(version 4.3.1).A clinical prediction nomogram was developed to visualize risk stratification,with model performance evaluated through receiver operating characteristic(ROC)curve analysis,calibration plots,and decision curve analysis(DCA).Internal validation was conducted using 1,000-cycle bootstrap resampling to ensure model generalizability.
文摘This paper is concerned with design-ing symbol labeling for a low-density parity-check(LDPC)-coded delayed bit-interleaved coded modu-lation(DBICM)scheme in a two-way relay channel(TWRC).We first present some properties of symbol labeling within a phase shift keying(PSK)modula-tion.These properties reduce the candidate labeling search space.Based on this search space,we take DBICM capacity as the cost function and propose a general method for optimizing symbol labeling by em-ploying the differential evolution algorithm.Numeri-cal results show that our labeling obtains a signal-to-noise ratio(SNR)gain up to 0.45 dB with respect to Gray labeling.
基金supported by the National Key Research and Development Program of China(2021YFD2100700)the National Natural Science Foundation of China(32021005)+1 种基金the 111 project(BP0719028)the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province.
文摘Irritable bowel syndrome-diarrhea(IBS-D)is a prevalent functional bowel disease severely impairs the quality of life of patients.Visceral hypersensitivity(VH)is the main symptom of IBS-D.Probiotics have been found to effectively alleviate VH.In this study,neonatal maternal separation(NMS)was used to induce VH in 72 rats and investigated the effects of daily gavage of 3×10^(9) CFU of Lactobacillus and Bifidobacterium on alleviating the symptoms of IBS-D and behavioral interventions,as well as exploring potential mechanisms.The results demonstrated that L.acidophilus and B.breve could alleviate the symptoms of IBS-D such as VH and increased frequency of bowel movements,as well as improving non-spatial memory in NMS rats.These effects were achieved by modulating the composition of gut microbiota and metabolites(including short-chain fatty acids,deoxycholic acid and adenosine),and by regulating the expression of genes and proteins associated with the NGF/TrkA signaling pathway,tryptophan metabolism,and inflammatory factors in the hippocampus.This finding suggests that L.acidophilus and B.breve have promising potential for the alleviation of IBS.
文摘BACKGROUND Delayed post-pancreatectomy hemorrhage(PPH)is life-threatening,and endovascular interventions show promise.This retrospective study aimed to evaluate endovascular treatment outcomes for delayed PPH and identify mortality risk factors.AIM To conduct a single-center retrospective study of 88 patients with delayed PPH to systematically evaluate the clinical efficacy of endovascular treatment,identify independent risk factors for six-month mortality,and propose and validate a predictive model for individualized management of high-risk patients.METHODS This retrospective analysis included 88 patients with delayed PPH treated by endovascular intervention.Patients were stratified into survival(n=64)and mortality(n=24)groups.Clinical and procedural variables were assessed using univariate and multivariate logistic regression.Significant predictors were incorporated into a prognostic nomogram.Model performance was assessed through discrimination(area under the receiver operating characteristic curve),calibration,and decision curve analysis.RESULTS Technical and clinical success rates were 92.0%and 60.2%,respectively.The overall six-month mortality rate was 27.3%(24/88).Independent predictors of mortality included advanced age,prolonged operative time,shorter hospital stay,intra-abdominal infection,coagulation dysfunction,common hepatic artery bleeding,and failure to achieve clinical success.The nomogram demonstrated excellent discrimination(area under the receiver operating characteristic curve=0.943),with good calibration and favorable net benefit on decision curve analysis.CONCLUSION We proposed and validated a predictive nomogram for six-month mortality following endovascular treatment for delayed PPH.The model facilitates individualized risk stratification and may guide clinical decision-making.Early identification of high-risk patients-particularly older individuals or those with infection or coagulopathy-and prompt,personalized intervention may improve outcomes in this high-risk population.
基金Supported by Science and Technology Plan Project of Zhongshan City(2022B1126).
文摘[Objectives]To explore the mechanism of action of Tongxieyaofang ultrafine granular powder in treating visceral hypersensitivity in rats with diarrhea-predominant irritable bowel syndrome(IBS-D)based on enteric glial cells(EGCs).[Methods]Eighty-four healthy male Wistar rats of SPF grade were selected and randomly assigned to seven groups,each comprising 12 rats:a normal control group,a model control group,a traditional Tongxieyaofang granular powder group(4.060 g/kg),three Tongxieyaofang ultrafine granular powder groups at low,medium,and high doses(1.015,2.030,and 4.060 g/kg of raw drug,respectively),and a pinaverium bromide group(0.018 g/kg).With the exception of the normal control group,all other groups were subjected to an IBS-D visceral hypersensitivity sensitivity model in rats developed by the chronic water avoidance stress method.Three days post modeling,the rats received continuous oral gavage administration for 8 d.Following the treatment period,serum and colon tissue samples were collected from each group.The BDNF level in the serum was quantified using ELISA.Additionally,the protein expression levels of GFAP,BDNF,and TrkB in colon tissues were assessed via Western blot assay.[Results]Compared to the normal control group,the serum BDNF levels in the model control group were significantly elevated(P<0.01).In contrast,each treatment group exhibited a significant reduction in serum BDNF levels relative to the model control group(P<0.01).Furthermore,the protein expression levels of GFAP,BDNF,and TrkB in colon tissue were significantly higher in the model control group compared to the normal control group(P<0.05,P<0.01).Conversely,these protein expressions were significantly decreased in each treatment group compared to the model control group(P<0.05,P<0.01).[Conclusions]Tongxieyaofang ultrafine granular powder effectively alleviates visceral sensitivity in IBS-D rats and inhibits the activation of EGCs,speculating that its mechanism of action involves the suppression of abnormal EGC activation.
基金supported by the National Natural Science Foundation of China(Grant No.82302173).
文摘Background:Contrast-enhanced magnetic resonance neurography(ceMRN)can enhance brachial plexus visualization and quality of imaging.However,the interval between contrast injection and scanning that provides the highest-quality images is not known.Methods:Fifteen patients underwent brachial plexus imaging using the 3D T2-NerveView sequence with a scanning duration of 5 min.A consecutive six-phase scan was initiated immediately at the start of contrast agent injection.Subsequently,all patients'images were classified into six groups according to the phases:group A(phase 1,delay 0 min),group B(phase 2,delay 5 min),group C(phase 3,delay 10 min),group D(phase 4,delay 15 min),group E(phase 5,delay 20 min),and group F(phase 6,delay 25 min).The image quality in each group was assessed based on nerve signal(signalnerve),muscle signal(signalmuscle),lymph node signal(signallymph node),background noise(BN),signal-to-noise ratio(SNR),contrast-to-noise ratio(CNR),and subjective score.Results:Signalnerve,signalmuscle,BN,and SNR did not significantly differ among the six groups(p>0.05).However,significant differences(p<0.05)were observed in signallymph node(F=16.067),CNR(F=9.495),and subjective score(χ^(2)=23.586).As the scanning delay increased,signallymph node intensity gradually increased whereas the CNR gradually decreased.The subjective score was significantly higher in groups B(4.830.24),C(4.900.21),D(4.870.30),E(4.830.31),and F(4.830.31)than in group A(4.470.30).Conclusion:We recommend performing brachial plexus ceMRN 5 min after contrast injection.With this delay,the brachial plexus can be visualized optimally with minimal interference from background signals.
基金support and funding from the National Natural Science Foundation of China(No.52174047)。
文摘Hydrogels are widely used in reservoir flow control to enhanced oil recovery.However,challenges such as environmental contamination from conventional crosslinkers,poor solubility of crosslinking agents,and short gelation times under high-temperature conditions(e.g.,150℃)have hindered their practical application.Herein,we present the synthesis of amine-functionalized carbon quantum dots(NH_(2)-CQDs),which act as both a nano-crosslinker and a nano-reinforcing agent within hydrogel systems.The NH_(2)-CQDs-incorporated hydrogel can remain stability for 300 days under the conditions of a mineralization degree of 2.11×10^(4)mg/mL and 170℃,and has high tensile strength(371 kPa),good toughness(49.6 kJ/m~3),excellent viscoelasticity(G'=960 Pa,G"=460 Pa)and shear resistance.In addition,NH_(2)-CQDs adds many hydroxyl groups to the hydrogel,which can be attached to the surface of various substances.At the same time,micro-nano capsules containing NH_(2)-CQDs were formed by self-assembly of hydrophobic SiO_(2)on water droplets,the NH_(2)-CQDs solution is encapsulated in a capsule,and when stimulated by external conditions(temperature,pH,surfactant),the capsule releases the NH_(2)-CQDs solution,this method greatly delays the crosslinking time between polymer and crosslinker at high temperature.Under the condition of 170℃and pH=7,the gelation time of 10%hydrophobic SiO_(2)coated hydrogel is 44 times that of uncoated hydrogel,which can be effectively used for deep formation flow control,and CQD give hydrogels fluorescence properties that can be used for underground signal tracking.
基金Supported by the Excellent Youth Project of Anhui Universities,No.2022AH030065National Natural Science Foundation of China,No.82474224 and No.82405244+3 种基金Anhui Provincial Natural Science Foundation,No.2408085MH223Open Projects of Anhui Province Key Laboratory of Meridian Viscera Correlationship,No.2024AHMVC04Research Project of Xin’an Medical and Chinese Medicine Modernization Research Institute,No.2023CXMMTCM016the Anhui Province Scientific Research Planning Project,No.2022AH050438.
文摘BACKGROUND Visceral hypersensitivity is the core pathogenesis of irritable bowel syndrome(IBS)and is often accompanied by negative emotions such as anxiety or depression.Paraventricular hypothalamic nucleus(PVN)corticotropin-releasing factor(CRF)is involved in the stress-related gastrointestinal dysfunction.Electroacupuncture(EA)has unique advantages for the treatment of visceral hypersensitivity and negative emotions in IBS patients.However,the underlying mechanisms remain unclear.AIM To investigate the pathological mechanisms visceral hypersensitivity and negative emotions in IBS,as well as the effect mechanism of EA.METHODS A model of diarrhoeal IBS(IBS-D)with negative emotions was prepared by chronic restraint combined with glacial acetic acid enema.The effect of EA was verified by abdominal withdrawal reflex and open-field test.PVN CRFcolonic mast cell(MC)/transient potential receptor vanilloid type 1(TRPV1)pathway was detected by immunofluorescence,Western blot,ELISA,and toluidine blue staining.Moreover,PVN CRFergic neurons were activated or inhibited by chemogenetical technique to observe the changes of effect indicator.RESULTS In the model group,IBS-D symptoms and negative emotions were successfully induced.Notably,the combination of Baihui(GV20)with Tianshu(ST25)and Dachangshu(BL25)acupoints showed the greatest efficacy in improving the negative emotions and visceral hypersensitivity in model mice.Furthermore,we found that EA inhibited overactivated PVN CRFergic neurons and the overexpression of serum CRF,colonic CRF,CRF-receptor 1(CRFR1),mast cell tryptase(MCT),protease-activated receptor 2 and TRPV1 in model mice.Moreover,we found that activating PVN CRFergic neurons induced negative emotions and visceral hypersensitivity in normal mice;however,inhibiting PVN CRFergic neurons alleviated negative emotions and intestinal symptoms in model mice and decreased the expression of colonic CRF-R1,MCT,and TRPV1.CONCLUSION This research highlights the key role of PVN CRF-MC CRF-R1 and the downstream MC/TRPV1 pathway in the pathological process of IBS-D and the mechanism of the effect of EA.
