OBJECTIVE: To explore the peripheral neural mechanism underlying representation along the distribution of stomach meridian induced by intestinal inflammatory reaction using diarrhea predominant-irritable bowel syndrome (IBS-D) mice. METHODS: Among 62 healthy male C57BL/6 mice of clean grade, 12 mice were randomly selected and divided into a control group and a model group, 6 mice in each group, additionally, 12 mice were randomly selected and divided into a Tianshu group, a Liangqiu group and a Zusanli group, 4 mice in each group. In the model group, citrobacter was administered orally to establish IBS-D model. In the control group and the model group, the visceral pain threshold was observed using fecal colorectal distension (fCRD) induced electromyography of external oblique muscle, the positive cell number of neutrophil in the colonic muscularis was detected by myeloperoxidase (MPO) staining, the number, location and distribution rule of Evans blue (EB) extravasation points were observed by injection of EB staining solution into the tail vein. In the Tianshu group, the Liangqiu group and the Zusanli group, fluorescent dye Dil was injected at bilateral "Tianshu" (ST25), "Liangqiu" (ST34) and "Zusanli" (ST36) respectively, to observe the dye-positive cell number in different dorsal root ganglion (DRG) segments. In the control group and the model group, the activation of satellite glial cells (SGCs) in different DRG segments was observed by immunofluorescence. RESULTS: Compared with the control group, in the model group, the area under curve of electromyography of external oblique muscle was increased at fCRD of 25, 50 and 75 μL distilled water (P<0.001, P<0.01); the MPO-positive cell number of neutrophil in the colonic muscularis was increased (P<0.01). Few EB extravasation points could be found in the control group, while there were much more EB extravasation points observed in the model group, which was specially distribution in the area of stomach meridian, from "Huaroumen" (ST24) to "Zusanli" (ST36), as well as the surface area dominated by L₂-L₅ segment of the spinal cord. The Dil-positive cells were mainly exhibited in the DRG of T₁₁, L₅ and L₄ segments in the Tianshu group, the Liangqiu group and the Zusanli group, respectively. Compared with the control group, the ratio of glial fibrillary acidic protein (GFAP)/glutamine synthetase (GS) co-expression was increased in the DRG of T₁₁, L₄ and L₅ segments in the model group (P<0.05, P<0.01). CONCLUSION The activation of SGCs within DRG of T₁₁, L₄ and L₅ segments may relate closely to the occurrence of the representation along the stomach meridian distribution in IBS-D mice.
Animals ; Male ; Mice ; Irritable Bowel Syndrome/therapy* ; Mice, Inbred C57BL ; Meridians ; Stomach/physiopathology* ; Humans ; Acupuncture Points ; Disease Models, Animal

Objective:To compare the efficacy of whole blood (WB) versus component therapy (COMP) in the resuscitation of patients with traumatic shock.Methods:A systematic literature search was conducted using PubMed and Embase databases for English literature published from January 2006 to December 2023. Studies on the comparative efficacy of WB versus COMP in resuscitation of patients with traumatic shock were all included. Patients were categorized according to the initial transfusion strategies into WB group and COMP group. Primary outcome indicators were extracted and subjected to meta-analysis, including transfusion requirements after admission (4-hour red blood cell requirement, 4-hour plasma requirement, 4-hour total transfusion volume, 24-hour red blood cell requirement, 24-hour plasma requirement, and 24-hour total transfusion volume), length of hospital stay, length of ICU stay, and mortality rates (early mortality, 24-hour mortality, late mortality, and in-hospital mortality, and 24-hour mortality with multiple variables adjusted).Results:Twenty-seven studies involving 15 176 patients (4 692 patients in WB group and 10 484 in COMP group) were included. Meta-analysis results indicated that the 4-hour red blood cell requirement (SMD=-0.44, 95% CI -0.69, -0.19, P<0.01), 4-hour plasma requirement (SMD=-0.25, 95% CI -0.50, -0.01, P<0.05), 24-hour red blood cell requirement (SMD=-0.22, 95% CI -0.36, -0.09, P<0.01), and 24-hour mortality with multiple variables adjusted ( OR=0.78, 95% CI 0.68, 0.91, P<0.05) were significantly reduced in WB group. No significant differences were observed between the two groups regarding 4-hour total transfusion volume, 24-hour plasma requirement, 24-hour total transfusion volume, length of hospital stay, length of ICU stay, early mortality, 24-hour mortality, late mortality, and total in-hospital mortality ( P>0.05). Conclusions:WB demonstrates certain advantages over COMP in the resuscitation of patients with traumatic shock by reducing 4-hour red blood cell requirement, 4-hour plasma requirement, 24-hour red blood cell requirement, and 24-hour mortality with multiple variables adjusted. However, WB and COMP demonstrate comparable effectiveness in reducing 4-hour total transfusion volume, 24-hour plasma requirement, 24-hour total transfusion volume, early mortality rate, 24-hour mortality rate, late mortality rate, and in-hospital mortality.

Objective:To explore the characteristics of the brain functional networks in children with spastic cerebral palsy (SCP) while at rest and to correlate them with motor functioning.Methods:Thirty-six children with SCP were enrolled as the SCP group, while thirty-four age-matched healthy children were recruited as the control group (the HC group). Functional near-infrared spectroscopy was used to detect changes in the concentration of oxygenated hemoglobin in the children′s cerebral cortex while at rest. The left prefrontal cortex (LPFC), right prefrontal cortex (RPFC), left motor cortex (LMC), and right motor cortex (RMC) were selected as regions of interest. Phase locking values (PLVs) were used to evaluate the strength of functional connectivity (FC) among these brain regions, and graph theory methods were applied to analyze the topological properties of the brain networks. Motor functioning was assessed using the gross motor function measure (GMFM).Results:The analyses of FC strength revealed that the SCP group had significantly weaker FC among all of the regions of interest while at rest compared to the HC group. Their PLVs for LPFC-RPFC, LPFC-RMC, RPFC-RMC and LMC-RMC connectivity were all significantly smaller. Graph theory analysis showed that the SCP group had significantly lower global efficiency (GE) and smaller clustering coefficients (CCs) and network density (D), while their characteristic path lengths were significantly longer. According to the correlation analysis, the PLVs for LMC-RMC connections in the SCP group were positively correlated with their scores on dimensions D and E of the GMFM ( r=0.496 and r=0.579 respectively). GE ( r=0.587 and r=0.642) and CC ( r=0.318 and r=0.759) showed similar significant positive correlations with GMFM dimensions D and E. Conclusions:At rest, the functional networks in the brains of children with SCP exhibit abnormalities closely associated with their motor dysfunction.

The aim of this study was to qualitatively and quantitatively detect coronavirus(CoV)in the feces of bats from Qinghua Cave,Yunnan Province,China.CoV was qualitatively tested with reverse transcription polymerase chain reaction(RT-PCR),and homology and genetic evolution were analyzed with bioinformatics software.The established reverse transcription real-time fluores-cence quantitative PCR(qRT-PCR)method was applied to CoV quantification in bat feces.The positivity rate of CoV in 306 fecal samples collected from the fulvous fruit bat(Rousettus leschenaultia)was 7.8%(24/306)according to RT-PCR.All 24 strains of CoV belonged to β-CoV,and showed a similarity of 86.8%-100.0%at the nucleotide level and 95.2%-100.0%at the amino acid level,with respect to other β-CoV sequences in the NCBI database.The positivity rate of CoV was 18.6%(57/306)according to qRT-PCR,a value higher than that according to RT-PCR(χ2=25.3,P<0.05).The mean β-CoV load was 1.3×103 copies/μL.In conclusion,the bats in Qinghua Cave,Yunnan Province,carried CoV belonging to β-CoV.The established qRT-PCR method achieved good sensitiv-ity,accuracy,reproducibility,and a higher detection rate than that of RT-PCR,and can be used for rapid detection of β-CoV in bats.

Objective To investigate the association between the TyG index,its modified variants,and the risk of developing colorectal cancer(CRC).Methods This study included a total of 93,177 participants from the 2006 Kailuan Group health examination cohort.Participants were categorized into four quartiles(Q1-Q4)according to their TyG and modified TyG indices.Follow-up began at the baseline examination,with incident CRC as the primary outcome.Participants were censored at the time of CRC diagnosis,death,or the end of the study,whichever occurred first.The dose-response relationship between TyG and its modified indices and the risk of CRC was evalu-ated using restricted cubic splines(RCS)in conjunction with Cox proportional hazards regression models,yielding hazard ratios(HRs)and 95%confidence intervals(CIs).To compare the strength of associations between TyG and its modified versions(TyG-BMI,TyG-WC,TyG-WHR,TyG-WHtR,TyG-WWI)and CRC risk,HRs for CRC per one standard deviation increase in each index were calculated and compared.Results Both the TyG index and its modified variants demonstrated a significant dose-response relationship with the risk of CRC incidence.Specifically,for the TyG index,each 1-standard deviation(SD)increase was associated with a 1.17-fold(95%CI:1.09～1.27)higher risk of CRC.Compared with the first quartile(Q1),the third quartile(Q3)and fourth quartile(Q4)exhibited a 1.25-fold(95%CI:1.01～1.55)and 1.26-fold(95%CI:1.01～1.57)increased risk,respectively.For TyG-BMI,each 1-SD increase was linked to a 1.20-fold(95%CI:1.07～1.35)elevated CRC risk.Compared with Q1,Q3 and Q4 showed a 1.32-fold(95%CI:1.06～1.64)and 1.51-fold(95%CI:1.21～1.88)increase,respectively.Regarding TyG-WC,each 1-SD increment was associated with a 1.22-fold(95%CI:1.13～1.32)higher CRC risk,with Q3 and Q4 showing a 1.35-fold(95%CI:1.08～1.70)and 1.56-fold(95%CI:1.24～1.96)increased risk compared to Q1.For TyG-WHtR,each 1-SD increase was associated with a 1.24-fold(95%CI:1.08-1.42)higher CRC risk.Compared with Q1,Q2,Q3,and Q4 demonstrated a 1.31-fold(95%CI:1.03～1.66),1.55-fold(95%CI:1.23～1.95),and 1.60-fold(95%CI:1.27～2.02)increase,respectively.In the case of TyG-WHR,each 1-SD increase was associated with a 1.19-fold(95%CI:1.10～1.29)higher CRC risk,with Q4 showing a 1.42-fold(95%CI:1.14～1.77)increased risk compared to Q1.Finally,for TyG-WWI,each 1-SD increase was associated with a 1.22-fold(95%CI:1.13～1.32)elevated CRC risk,with both Q3 and Q4 showing a 1.58-fold increase(Q3:95%CI:1.26～1.98;Q4:95%CI:1.25～1.99).Stratified analyses by sex and age consistently revealed significant associations between the TyG index and its modified variants and CRC risk.Furthermore,these indices were independently associated with the incidence of both colon cancer and rectal cancer.Conclusions(1)Elevated levels of the TyG index and its modified variants are independent risk factors for CRC.(2)Both the TyG index and its modified forms demonstrate a significant dose-response association with the incidence of CRC.(3)Among the modified TyG indices,TyG-WWI,TyG-WHtR,TyG-BMI,TyG-WC,and TyG-WHR showed stronger correlations with CRC risk compared to the original TyG index.

Objective To investigate the factors influencing the efficacy of intravesical Bacille Calmette-Guérin(BCG)instillation after transurethral resection of bladder tumor(TURBT)in patients with intermediate-and high-risk non-muscle invasive bladder cancer(NMIBC),and to construct a prediction model for recurrence after BCG treatment.Methods A retrospective cohort study was conducted on the subjected patients diagnosed with intermediate-and high-risk NMIBC undergoing TURBT followed by standard BCG instillation.The 110 patients treated in Department of Urology of Army Medical Center of PLA from January 2018 to December 2023 were assigned into a training set,while the 52 patients treated at Department of Urology of General Hospital of Central Theater Command from January 2015 to December 2020 were into an external validation set.A total of 17 variables were included and analyzed.Univariate and multivariate Cox regression analyses were performed to identify factors associated with recurrence after BCG instillation,and nomograms were plotted to predict 1-year,3-year,and 5-year recurrence-free survival(RFS).Calibration curve,decision curve analysis(DCA),and receiver operating characteristic(ROC)curve analysis were conducted for internal and external validation to evaluate the predictive performance and clinical utility of the model.Results In the training set,26 patients(23.64%)experienced recurrence during the follow-up period,with a median RFS of 32.00(18.00～50.50)months.Univariate Cox regression analysis suggested that platelet count,eosinophil to lymphocyte ratio(ELR),neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),systemic immune inflammation(SII)index,and neutrophil-monocyte to lymphocyte ratio(NMLR),pathological T1 stage(pT1)tumor and hemoglobin,albumin,lymphocyte,and platelet(HALP)score were potential factors influencing recurrence after BCG instillation.Multivariate Cox regression analysis identified high HALP score(HR=0.185,95%CI:0.046～0.736,P=0.017)as an independent protective factor,while high ELR(HR=3.599,95%CI:1.505～8.608,P=0.004)and pT1 stage(HR=3.240,95%CI:1.191～8.818,P=0.021)were independent risk factors for recurrence.Based on this,a nomogram prediction model was constructed.The calibration curves demonstrated good agreement between predicted and actual 1-,3-,and 5-year recurrence risks.Decision curve analysis indicated clinical utility across a wide threshold probability range.In the training set,the model showed strong predictive performance for 1-(AUC=0.842),3-(AUC=0.847),and 5-year(AUC=0.887)recurrence risks,which was further validated in the external cohort.Conclusion Higher HALP score prior to BCG instillation therapy is a protective factor against tumor recurrence,while higher ELR and pT1 stage are risk factors.Our nomogram prediction model based on HALP score,ELR and pathological T stage,can identify individuals at high risk of recurrence after BCG instillation therapy.

Druggability evaluation is one of the core processes in new drug development, yet the inaccuracy and high cost of existing in vitro liver models have been a major technical bottleneck, leading to an increasing demand from the pharmaceutical industry for reliable in vitro liver models to enhance the efficiency of new drug research and development. Traditional animal models and in vitro 2D culture models have their limitations in simulating in vivo physiological and pathological conditions, making it challenging to accurately predict drug efficacy and safety. With the advancement of microfluidic technology, in vitro cell culture, and biosensor technology, liver-on-a-chip (LOC) has garnered increasing attention in the field of new drug development in recent years, and is expected to become a powerful tool for addressing the challenges in druggability evaluation. While introducing the construction technology of LOC, this article mainly summarizes the research and application of existing LOC from the perspectives of disease model construction, drug metabolism research, and drug safety evaluation. Furthermore, it analyzes the role of LOC in druggability evaluation and discusses the current challenges and prospects in this field.

Objective To investigate the association between the TyG index,its modified variants,and the risk of developing colorectal cancer(CRC).Methods This study included a total of 93,177 participants from the 2006 Kailuan Group health examination cohort.Participants were categorized into four quartiles(Q1-Q4)according to their TyG and modified TyG indices.Follow-up began at the baseline examination,with incident CRC as the primary outcome.Participants were censored at the time of CRC diagnosis,death,or the end of the study,whichever occurred first.The dose-response relationship between TyG and its modified indices and the risk of CRC was evalu-ated using restricted cubic splines(RCS)in conjunction with Cox proportional hazards regression models,yielding hazard ratios(HRs)and 95%confidence intervals(CIs).To compare the strength of associations between TyG and its modified versions(TyG-BMI,TyG-WC,TyG-WHR,TyG-WHtR,TyG-WWI)and CRC risk,HRs for CRC per one standard deviation increase in each index were calculated and compared.Results Both the TyG index and its modified variants demonstrated a significant dose-response relationship with the risk of CRC incidence.Specifically,for the TyG index,each 1-standard deviation(SD)increase was associated with a 1.17-fold(95%CI:1.09～1.27)higher risk of CRC.Compared with the first quartile(Q1),the third quartile(Q3)and fourth quartile(Q4)exhibited a 1.25-fold(95%CI:1.01～1.55)and 1.26-fold(95%CI:1.01～1.57)increased risk,respectively.For TyG-BMI,each 1-SD increase was linked to a 1.20-fold(95%CI:1.07～1.35)elevated CRC risk.Compared with Q1,Q3 and Q4 showed a 1.32-fold(95%CI:1.06～1.64)and 1.51-fold(95%CI:1.21～1.88)increase,respectively.Regarding TyG-WC,each 1-SD increment was associated with a 1.22-fold(95%CI:1.13～1.32)higher CRC risk,with Q3 and Q4 showing a 1.35-fold(95%CI:1.08～1.70)and 1.56-fold(95%CI:1.24～1.96)increased risk compared to Q1.For TyG-WHtR,each 1-SD increase was associated with a 1.24-fold(95%CI:1.08-1.42)higher CRC risk.Compared with Q1,Q2,Q3,and Q4 demonstrated a 1.31-fold(95%CI:1.03～1.66),1.55-fold(95%CI:1.23～1.95),and 1.60-fold(95%CI:1.27～2.02)increase,respectively.In the case of TyG-WHR,each 1-SD increase was associated with a 1.19-fold(95%CI:1.10～1.29)higher CRC risk,with Q4 showing a 1.42-fold(95%CI:1.14～1.77)increased risk compared to Q1.Finally,for TyG-WWI,each 1-SD increase was associated with a 1.22-fold(95%CI:1.13～1.32)elevated CRC risk,with both Q3 and Q4 showing a 1.58-fold increase(Q3:95%CI:1.26～1.98;Q4:95%CI:1.25～1.99).Stratified analyses by sex and age consistently revealed significant associations between the TyG index and its modified variants and CRC risk.Furthermore,these indices were independently associated with the incidence of both colon cancer and rectal cancer.Conclusions(1)Elevated levels of the TyG index and its modified variants are independent risk factors for CRC.(2)Both the TyG index and its modified forms demonstrate a significant dose-response association with the incidence of CRC.(3)Among the modified TyG indices,TyG-WWI,TyG-WHtR,TyG-BMI,TyG-WC,and TyG-WHR showed stronger correlations with CRC risk compared to the original TyG index.

Objective To investigate effects of Cordyceps sinensis(CS)on high glucose(HG)induced podocyte injury by regulating the adenylate activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)signaling pathway.Methods Mouse podocytes were cultured in vitro and divided into the normal glucose(NG)group,the HG group,the HG+CS group,the HG+CS+autophagy inhibitor(HG+CS+3MA)group and the HG+CS+AMPK inhibitor(HG+CS+Compound C)group.Podocyte viability was detected by CCK-8 method.Western blot assay was used to detect the expression levels of podocyte marker proteins podocin and nephrin,autophagy-related proteins Beclin-1 and P62,and pathway related proteins p-AMPK and p-mTOR.Results Compared with the NG group,the cell viability of podocytes decreased,the expression levels of podocin,nephrin,Beclin-1 and p-AMPK protein were decreased,and the expression levels of P62 and p-mTOR protein were increased in the HG group(P＜0.05).Compared with the HG group,the cell viability of podocytes was increased,the expression levels of podocin,nephrin,Beclin-1 and p-AMPK protein were significantly increased(P＜0.05),and the expression levels of P62 and p-mTOR protein were decreased in the HG+CS group(P＜0.05).Compared with the HG+CS group,the cell viability decreased in the HG+CS+3MA group and the HG+CS+Compound C group(P＜0.05).Compared with the HG+CS group,the HG+CS+3MA group and the HG+CS+Compound C group showed decreased expression levels of podocin,nephrin and Beclin-1 protein,and increased expression of P62 protein(P＜0.05).Compared with the HG+CS group,the expression of p-AMPK protein decreased and the expression of p-mTOR protein increased in the HG+CS+Compound C group(P＜0.05).Conclusion Cordyceps sinensis may play a protective role in diabetic nephropathy by up-regulating AMPK/mTOR signaling pathway to induce podocyte autophagy,alleviate high glucose induced podocyte injury and apoptosis.

Objective To investigate effects of Cordyceps sinensis(CS)on high glucose(HG)induced podocyte injury by regulating the adenylate activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)signaling pathway.Methods Mouse podocytes were cultured in vitro and divided into the normal glucose(NG)group,the HG group,the HG+CS group,the HG+CS+autophagy inhibitor(HG+CS+3MA)group and the HG+CS+AMPK inhibitor(HG+CS+Compound C)group.Podocyte viability was detected by CCK-8 method.Western blot assay was used to detect the expression levels of podocyte marker proteins podocin and nephrin,autophagy-related proteins Beclin-1 and P62,and pathway related proteins p-AMPK and p-mTOR.Results Compared with the NG group,the cell viability of podocytes decreased,the expression levels of podocin,nephrin,Beclin-1 and p-AMPK protein were decreased,and the expression levels of P62 and p-mTOR protein were increased in the HG group(P＜0.05).Compared with the HG group,the cell viability of podocytes was increased,the expression levels of podocin,nephrin,Beclin-1 and p-AMPK protein were significantly increased(P＜0.05),and the expression levels of P62 and p-mTOR protein were decreased in the HG+CS group(P＜0.05).Compared with the HG+CS group,the cell viability decreased in the HG+CS+3MA group and the HG+CS+Compound C group(P＜0.05).Compared with the HG+CS group,the HG+CS+3MA group and the HG+CS+Compound C group showed decreased expression levels of podocin,nephrin and Beclin-1 protein,and increased expression of P62 protein(P＜0.05).Compared with the HG+CS group,the expression of p-AMPK protein decreased and the expression of p-mTOR protein increased in the HG+CS+Compound C group(P＜0.05).Conclusion Cordyceps sinensis may play a protective role in diabetic nephropathy by up-regulating AMPK/mTOR signaling pathway to induce podocyte autophagy,alleviate high glucose induced podocyte injury and apoptosis.