Objective:To investigate the prognostic factors for the risk of prolonged postoperative ileus (PPOI) after colorectal cancer resection.Methods:The clinical data of 896 patients undergoing radical colorectal cancer resection at Affiliated Hospital of Qingdao University between Jan 2016 and Dec 2022 were retrospectively analyzed. Patients were divided into PPOI group (59 cases) and non-PPOI group (837 cases) according to whether PPOI happened after surgery. Potential prognostic factors for the risk of developing PPOI were analyzed by univariate and multivariate Logistic regression. The receiver operating characteristic curve analysis was performed to assess the predictive power of potential prognosis factors.Results:Fifty-nine patients (6.5%) developed PPOI after radical colorectal cancer resection. Univariate and multifactorial logistic regression analyses showed that diabetes mellitus ( OR=2.360, P=0.018), preoperative albumin level <35 g/L ( OR=2.196, P=0.036), postoperative epidural analgesia ( OR=2.399, P=0.007), open surgery ( OR=3.413, P=0.001), and ICU hospitalization ≥ 48 h ( OR=6.134, P<0.001) were independent prognostic factors for PPOI. Combining the above prognostic factors to construct the receiver operating characteristic curve yielded an area under the curve of 0.806 (95% CI: 0.698-0.838), with an accuracy, sensitivity and specificity of 73.9%, 74.0%, 72.9%, respectively. Conclusion:Diabetes mellitus, preoperative albumin level, postoperative epidural analgesia, open surgery, and ICU hospitalization ≥ 48 h were risk factors for PPOI after radical colorectal cancer resection.

Objective To investigate effects of ligustilide(LIG)on proliferation,apoptosis,angiogenic mimicry and Ras homolog gene family member A(RhoA)/Rho associated coiled coil containing protein kinase 1(ROCK)signaling pathway in esophageal cancer cells.Methods Esophageal cancer cell line EC-109 was treated with LIG at concentrations of 0,12.5,25,50,100,and 200 μmol/L to detect cell activity,and the suitable concentration was selected for subsequent experiments.EC-109 cells were grouped into the control group,the LIG low,medium and high concentration groups(LIG-L,LIG-M and LIG-H groups),and the LIG-H+RhoA activator Naciclassine group(LIG-H+Naciclassine group).Edu was applied to detect cell proliferation,and flow cytometry was applied to detect cell apoptosis.Angiogenetic mimicry was observed.Western blot assay was applied to detect expression levels of proteins related to cell proliferation and apoptosis,and RhoA,ROCK proteins.Nude mouse tumor transplantation experiment was applied to verify the effect of LIG on the growth of esophageal cancer tumors.Immunohistochemistry was applied to detect expression levels of angiogenesis related factors(VEGF),RhoA and ROCK proteins in transplanted tumors.Results Compared with the control group,the vascular mimicry tubular structure of EC-109 cells decreased sequentially in the LIG-L group,the LIG-M group and the LIG-H group.The positive rate of Edu,the expression levels of Cyclin D1,Ki67,Bcl-2,RhoA and ROCK reduced in turn.P21,cell apoptosis rate,the expression of Bax and Caspase-3 increased in sequence(P＜0.05).Naciclasine,RhoA activator,partially reversed the effect of LIG on cell proliferation,apoptosis and vasculogenic mimicry of esophageal cancer cells.Nude mouse transplantation tumor experiment showed that compared with the control group,the growth rate of transplanted tumor showed down,tumor volume decreased and the expression levels of RhoA,ROCK and VEGF decreased in the LIG group(P＜0.05).Conclusion Ligustilide inhibits the proliferation and angiogenic mimicry of esophageal cancer cells by inhibiting RhoA/ROCK signaling pathway,and promotes the apoptosis of esophageal cancer cells.

Methamphetamine (Meth) abuse can cause serious mental disorders, including anxiety and depression. The gut microbiota is a crucial contributor to maintaining host mental health. Here, we aim to investigate if microbiota participate in Meth-induced mental disorders, and the potential mechanisms involved. Here, 15 mg/kg Meth resulted in anxiety- and depression-like behaviors of mice successfully and suppressed the Sigma-1 receptor (SIGMAR1)/BDNF/TRKB pathway in the hippocampus. Meanwhile, Meth impaired gut homeostasis by arousing the Toll-like receptor 4 (TLR4)-related colonic inflammation, disturbing the gut microbiome and reducing the microbiota-derived short-chain fatty acids (SCFAs). Moreover, fecal microbiota from Meth-administrated mice mediated the colonic inflammation and reproduced anxiety- and depression-like behaviors in recipients. Further, SCFAs supplementation optimized Meth-induced microbial dysbiosis, ameliorated colonic inflammation, and repressed anxiety- and depression-like behaviors. Finally, Sigmar1 knockout (Sigmar1^-/-) repressed the BDNF/TRKB pathway and produced similar behavioral phenotypes with Meth exposure, and eliminated the anti-anxiety and -depression effects of SCFAs. The activation of SIGMAR1 with fluvoxamine attenuated Meth-induced anxiety- and depression-like behaviors. Our findings indicated that gut microbiota-derived SCFAs could optimize gut homeostasis, and ameliorate Meth-induced mental disorders in a SIGMAR1-dependent manner. This study confirms the crucial role of microbiota in Meth-related mental disorders and provides a potential preemptive therapy.

OBJECTIVE To prepare Angelica•Cinnamomum（Angelica sinensis-Cinnamomum cassia ）self•microemulsion drug delivery system （AC•SMEDDS），and to optimize its formulation and characterize its preparation . METHODS Using Angelica• Cinnamomum mixed volatile oil as oil phase and model drug ，on the basis of selecting emulsifier and co -emulsifier and the optimization of their mass ratio range ，the formulation was optimized with central composite design •response surface methodology using the ratio of oil phase （Angelica•Cinnamomum mixed volatile oil ），mass ratio of emulsifier and co -emulsifier as factors ，the comprehensive score of volatile oil content ，particle size and emulsifying time as index . Morphology，particle size ，drug loading ， entrapped efficiency and stability of optimized AC•SMEDDS were characterized . RESULTS The optimum formulation of AC•SMEDDS contained the ratio of oil phase was 30%，and the mass ratio of emulsifier （EL•40）and co -emulsifier（ethanol）was 9∶1. Results of validation tests showed that the average particle size of AC•SMEDDS was （148.33±1.53）nm，and emulsifying time was （18.44±0.11）s. The comprehensive score was 0.68，relative deviation of which from the predicted value （0.70）was 2.86%. AC•SMEDDS prepared by optimal formulation was faint yellow ，uniform and transparent liquid ，and spherical particals with translucent edge were observed under transmission electron microscope . Calculated by ligustilide and cinnamaldehyde ，the drug loading was （7.58±0.03） and （4.17±0.01） mg/g，and entrapped efficiency was （93.25±0.01）% and （88.89±0.02）% ， respectively. No stratification or precipitation occurred after centrifugation at the speed of 10 000 r/min or placing within 7 （No.2019-0520） days at 4 and 25 ℃ . The contents of ligustilide and cinnamaldehyde were stable . Its particle size had no significant change after 50，100 and 200 times dilution by purified water . CONCLUTIONS AC•SMEDDS is prepared successfully and its formulation is optimized . The stability of the preparation is good .

Objective:To explore the changes of left atrial volume and function in patients with early diabetic nephropathy by four-dimensional auto left atrial quantification (4D Auto LAQ).Methods:Forty patients with early diabetic nephropathy (early diabetic nephropathy group), 40 patients with type 2 diabetes (diabetes group) in Henan Provincial People′s Hospital from March 2020 to April 2021 were selected, and 36 healthy volunteers (control group) were collected during the same period. The parameters of conventional echocardiography were measured, and the four-dimensional volume probe was used to obtain the complete left atrial volume image in 5 cardiac cycles. The 4D Auto LAQ software on the EchoPAC workstation was used for analysis to obtain the left atrial volume and strain indicators: left atrial (LA) maximum volume (LAVmax), left atrial minimum volume (LAVmin), pre-systolic volume (LAVpreA), left atrial volume index (LAVImax), left atrial emptying volume (LAEV), left atrial emptying fraction (LAEF), and long axis and circumferential strains in left atrial reserve phase, pipeline phase and systolic phase (LASr, LASr-c; LAScd, LAScd-c; LASct, LASct-c). The differences of these parameters among 3 groups were analyzed.Results:There were no significant differences in interventricular septum end-diastolic thickness(IVSd), left ventricular posterior wall end-diastolic thickness(LVPWd), left ventricular end-diastolic dimension(LVIDd), left ventricular ejection fraction(LVEF), and E/A (ration of early to late diastolic peak flow velocity of mitral orifice) among 3 groups (all P>0.05), and left atrial diameter(LAD), relative wall thickness(RWT), and E/e′ (ration of early diastolic peak flow velocity of mitral orifice to early diastolic velocity of lateral mitral annulus) among 3 groups were significantly different (all P<0.05). Further pairwise comparison results showed that LAD was only significantly different between the early diabetic nephropathy group and control group ( P=0.001 2), and the differences in RWT and E/e′ were statistically significant among 3 groups (all P<0.05). There were no significant differences in LAEV, LAScd-c, and LASct-c among 3 groups (all P>0.05), and LAVmin, LAVmax, LAVpreA, LAVImax, LAEF, LASr, LAScd, LASct, and LASr-c among the 3 groups were significantly different (all P<0.05). The pairwise comparison showed that, compared with the control group and the diabetes group, LAVmin, AVpreA, and LAVImax in the early diabetic nephropathy group were increased, and LAEF, LAScd, LASct, and LASr-c were decreased (all P<0.05). Compared with the control group, LAVmax, LAVImax and LASct in the diabetes group were increased, and LAEF, LAScd, and LASr-c were decreased (all P<0.05). Conclusions:4D Auto LAQ technology can quantitatively evaluate the changes in left atrium volume and function in patients with early diabetic nephropathy. Patients with early diabetic nephropathy have an increase in left atrium volume and a decrease in strain value.

Objective:To develop an ex vivo normothermic mechanical perfusion(NMP)and compare the effect of air-oxygenated NMP versus oxygen-oxygenated NMP on reducing renal injury from donor after cardiac death(DCD).Methods:All kidneys from DCD rats were subjected to 30 min in situ warm ischemia after cardiac attest.And harvested kidneys were stored for 8h under static cold preservation after NMP for 2h.In experimental groups, kidneys were subjected to either air-oxygenated NMP(group A, n=6)or oxygen-oxygenated NMP(group O, n=6). Sham operation(group C, n=6)and DCD kidneys under static cold preservation without NMP(group SCS, n=6)were employed as controls.The evaluation parameters included creatinine(Cr), aspartate amino transferase(AST)and lactate dehydrogenase(LDH)in perfusate, pathological changes by hematoxylin-eosin(HE)staining, histological criteria, expressions of myeloperoxidase and intercellular adhesion molecular-1(ICAM-1)by immunohistochemistry and Western blot, tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)by enzyme-linked immunoadsorbent assay and level of malondialdehyde(MDA)by thiobarbital method and activity of superoxide dismutase(SOD)by WST-8 in renal tissues.Differences between two groups were analyzed by two-tailed unpaired Student's test and differences among more than two groups by one-way ANOVA.Results:Renal arterial oxygen tensions in NMP perfusate were(576.3±68.2)mmHg with oxygen-oxygenation and(137.0±39.1)mmHg with air-oxygenation.There was significant difference( P<0.05). The pathological injury scores in groups SCS, O and A by HE staining were(7.0±0.1), (5.0±0.9)and(2.5±0.5); injury scores and the expressions of renal proximal tubular epithelial cell vacuolar degeneration in groups O and A were lower than those in group SCS( P<0.05)and injury score in group A was lower than group O( P<0.05). In perfusate, the levels of △Cr, △AST and △LDH in groups O and A were(43.9±52.8)μmol/L and(12.6±3.5)μmol/L, (532.3±52.8)U/L and(49.1±50.4)U/L and(9998.0±2014.4)U/L and(1477.0±810.4)U/L.There were significant differences( P<0.05). In perfused kidneys, the MDA level and SOD activity in groups O and A were(0.192±0.018)mmol/g, (0.162±0.023)mmol/g, (0.6±0.3)×10 3 U/g, (1.7±0.4)×10 3 U/g; TNF-α and IL-6 levels in groups O and A were(124.376±19.635)and(89.331±13.123)ng/g, and(4.038±1.026)×10 3 and(1.774±0.518)×10 3 ng/g.After air-oxygenated NMP, lower renal damage indices were characterized by a lower MDA level and a higher SOD activity, the lower levels of TNF-α and IL-6 and the lower expressions of MPO and ICAM-1 than those in oxygen-oxygenated NMP( P<0.05). Conclusions:NMP with air-oxygenation mimics renal perfusion under physiological conditions and decreases oxidative stress and inflammation injury.It may confer a better retrieval in DCD kidney against warm ischemia injury.

ObjectiveThis study aims to investigate the efficacy and underlying mechanism of Da Chaihutang （DCHT） in treating hepatocellular carcinoma （HCC） in vitro and in vivo. MethodWe employed methyl thiazolyl tetrazolium （MTT） assay and crystal violet staining to observe the proliferation of Hepa1-6 liver cancer cells treated with DCHT at different doses （0， 125， 250， 500， 1 000 mg·L^-1） for different time periods （1， 2， 4， 8 days）. The orthotopic liver cancer model was established by injection of 1×10⁶ Hepa1-6 cells into mouse， and then the model mice were randomly assigned into six groups： blank， model， DCHT （0.21， 0.625， 1.875 g·kg^-1， ig， qd）， and positive control （5-fluorouracil， 25 mg·kg^-1， ip， qod）. After 14 days of administration， the mice were sacrificed， and the liver samples were collected and fixed in 4% paraformaldehyde for hematoxylin-eosin （HE） staining. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Cytoscape 3.7.2， STRING， and DAVID were used for the searching of the key targets of DCHT in treating HCC， the construction of protein-protein interaction （PPI） network， and the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment. Quantitative real-time PCR was performed to determine the mRNA level of interleukin-6 （IL-6） in Hepa1-6 cells and liver tissue. Western blotting was employed to measure the protein levels of the proteins involved in the mitogen-activated protein kinase （MAPK） and signal transducers and activators of transcription 3 （STAT3） signaling pathways. ResultDCHT （500， 1 000 mg·L^-1） treatment for 4 and 8 days inhibited the proliferation of Hepa1-6 cells in a dose- and time-dependent manner （P<0.05）. The in vivo assay showed that DCHT （high dose， 1.875 g·kg^-1） treatment for 14 days led to high differentiation and unobvious heterogeneity of HCC cells and small necrotic area compared with the model group. Network pharmacology analysis predicted that the potential targets of DCHT in the treatment of HCC were mainly the inflammation cytokines such as IL-6， interleukin-1β （IL-1β）， and tumor necrosis factor-alpha （TNF-α） in HCC microenvironment. The potential signaling pathways involved in the treatment were mainly associated with HCC growth and differentiation， including MAPK and STAT3 signaling pathways. Compared with the blank group， DCHT （1 000 mg·L^-1） treatment for 1， 2， 4， and 8 days down-regulated the mRNA level of IL-6 in Hepa1-6 cells （P<0.05）. Similar results were observed in the livers of mice treated with DCHT （0.625， 1.875 g·kg^-1）. The in vitro assay demonstrated that DCHT （1 000 mg·L^-1） treatment for 4 and 8 days and DCHT （500， 1 000 mg·L^-1） treatment inhibited the phosphorylation of extracellular signal-regulated kinases 1/2 （ERK1/2）， c-Jun NH₂-terminal kinase/stress-activated protein kinase （JNK）， p38 MAPK， and STAT3 in a dose- and time-dependent manner （P<0.05）. The in vivo assay showed that DCHT （0.625 and 1.875 g·kg^-1） treatment only inhibited the phosphorylation of p38 MAPK and STAT3 （P<0.05）. ConclusionThe present study indicates that DCHT can inhibit liver cancer cell proliferation by regulating p38 MAPK/IL-6/STAT3 signaling pathway.

Cyclodextrin metal-organic framework (CD-MOF) as a highly porous supramolecular carrier could be one of the solutions to the insolubility of isosteviol (STV). The solubility of STV was lower than 20.00 ng/mL at pH 1.0 and pH 4.5, whilst its solubility increased to 20,074.30 ng/mL at pH 6.8 and 129.58 ng/mL in water with a significant pH-dependence. The

Objective:The evaluate left ventricular myocardial work in maintenance hemodialysis (MHD) patients by non-invasive left ventricular pressure strain curve.Methods:Forty-eight patients undergoing maintenance hemodialysis were selected as the MHD group, and 33 healthy subjects were selected as the control group from Apr to Oct 2019 in Henan Provincial People′s Hospital. The differences of general clinical data, basic parameters of two-dimensional ultrasound including left ventricular end-diastolic diameter (LVDd), left ventricular end-systolic diameter (LVDs), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), stroke volume (SV), diastolic interventricular septal thickness (IVSd), left ventricular diastolic posterior wall thickness (LVPWd), left ventricular diastolic mass (LVDm), left ventricular systolic mass (LVSm), late diastolic tissue velocity (a′), early diastolic peak velocity/early diastolic tissue velocity (E/e′), A peak and cardiac output (CO), peak strain dispersion (PSD), and global work index (GWI), global work efficiency (GWE), global constructive work (GCW), global wasted work (GWW) and global long-axis strain (GLS) between two groups were compared, and the correlation between myocardial work parameters and conventional cardiac parameters was analyzed.Results:①In terms of comparison, LVDd, LVDs, LVEDV, LVESV, SV, IVSd, LVPWd, LVDm, LVSm, systolic blood pressure (SBP), diastolic blood pressure (DBP), a′, E/e′. A peak and CO of the MHD group were greater than those in the control group (all P<0.05), and e′ of the MHD group was lower ( P<0.05). ②In terms of comparison, PSD and GWW of the MHD group were greater than those of the control group (all P<0.05), while GLS and GWE of the MHD group was lower (all P<0.05). There were no statistically significant differences in GCW and GWI between two groups(all P>0.05). ③GWI was positively correlated with SBP, DBP and left ventricular ejection fraction (LVEF)( r1=0.442, P1=0.030; r2=0.477, P2=0.019; r3=0.431, P3=0.040), and negatively correlated with GLS and LVDs( r1=-0.576, P1=0.003; r2=-0.404, P2=0.050). GWW was positively correlated with GLS and PSD( r1=0.584, P1=0.003; r2=0.564, P2=0.004). GWE was positively correlated with LVEF( r=0.424, P=0.044), and negatively correlated with LVEDV, LVESV, PSD, GLS and LVDm( r1=-0.444, P1=0.034; r2=-0.490, P2=0.018; r3=-0.721, P3<0.001; r4=-0.738, P4<0.001; r5=-0.442, P5=0.035). GCW was positively correlated with LVEF and DBP( r1=0.494, P1=0.017; r2=0431, P2=0.035), and negatively correlated with GLS and LVDs( r1=-0.630, P1=0.001; r2=-0.419, P2=0.042). Conclusions:The non-invasive left ventricular pressure-strain curve combines blood pressure and strain. Compared with the GLS, it can accurately assess left ventricular myocardial work in maintenance hemodialysis patients and predict potential left ventricular function changes in maintenance hemodialysis patients.

Stem cell research has become a frontier in the field of life sciences, and provides an ideal model for exploring developmental biology problems such as embryogenesis, histiocytosis, and gene expression regulation, as well as opens up new doors for clinical tissue defective and inheritance diseases. Among them, menstrual blood-derived stem cells (MenSCs) are characterized by wide source, multi-directional differentiation potential, low immune rejection characteristics. Thus, MenSCs can achieve individual treatment and have the most advantage of the clinical application. The central nervous system, including brain and spinal cord, is susceptible to injury. And lethality and morbidity of them tops the list of all types of trauma. Compared to peripheral nervous system, recovery of central nervous system after damage remains extremely hard. However, the treatment of stem cells, especially MenSCs, is expected to solve this problem. Therefore, biological characteristics of MenSCs and their treatment in the respect of central nervous system diseases have been reviewed at home and abroad in recent years, so as to provide reference for the treatment of central nervous system diseases.