ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

Nonalcoholic fatty liver disease （NAFLD） has become the most common chronic liver disease in the world， and it is also one of the main causes of liver cirrhosis and hepatocellular carcinoma， so it is particularly important to curb the development and progression of NAFLD in a timely manner. However， due to its complex pathogeneses， there are currently no effective methods for radical treatment. As a new generation of probiotics， Akkermansia muciniphila （Akk bacteria） can improve metabolic disorders of the body， and more and more studies have shown that Akk bacteria have a potential therapeutic effect on metabolic diseases， especially NAFLD. Therefore， this article briefly reviews the mechanism of action of Akk bacteria in NAFLD， in order to provide new ideas for improving the treatment of NAFLD and creating new therapies.

Objective To observe the value of pseudo-continuous arterial spin labeling(PCASL)MRI for evaluating renal function in patients with renal occupying lesions.Methods Totally 56 patients with single renal occupying lesion were retrospectively enrolled.The left and right side kidneys were divided into normal renal function group(normal group,30 ml/min)and damaged renal function group(damaged group,＜30 ml/min)according to glomerular filtration rate(GFR)measured with 99Tcm-DTPA dynamic renal imaging,respectively.The total renal blood flow(tRBF)and cortical renal blood flow(cRBF)were calculated using total nephrometry and cortical nephrometry based on PCASL MRI,respectively,then GFR,tRBF and cRBF were compared between groups on the same side.Receiver operating characteristic curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of tRBF and cRBF for assessing unilateral renal injury.Pearson correlation analysis was performed to observe the correlations of tRBF and cRBF with GFR.Results GFR,tRBF and cRBF in left/right damaged group were all significantly lower than those in ipsilateral normal group(all P＜0.05).AUC of tRBF and cRBF for assessing left renal injury was 0.823 and 0.813,respectively,being not significantly different(P＞0.05).AUC of tRBF and cRBF for assessing right renal injury was 0.940 and 0.922,respectively,being not significantly different(P＞0.05).No obvious correlation of bilateral tRBF nor cRBF with GFR was found(all P＞0.05).Conclusion PCASL MRI could effectively evaluate renal function in patients with renal occupying lesion,and the efficacy of total nephrometry was comparable to that of cortical nephrometry.

Purpose To explore the value of iodine concentration(IC)and effective atomic number(Zeff)derived from dual-layer spectral detector CT in diagnosing the regional lymph nodes of gastric cancer.Materials and Methods From May 2021 to September 2022,108 patients pathologically confirmed with gastric cancer(92 non-metastatic lymph nodes and 116 metastatic lymph nodes),who underwent dual-phase enhanced dual-layer spectral detector CT scanning preoperatively in the Second Affiliated Hospital of Guangzhou University of Chinese Medicine,were included in the study.The imaging and clinical data of all cases were collected,retrospectively.According to preoperative CT images,the short diameter,margin and enhancement homogeneity of the lymph nodes were evaluated.The IC and Zeff were obtained from the delineated region of interest of the solid portion of the maximum layer of the target lymph nodes,and the normalization IC(nIC)and normalization Zeff(nZeff)were calculated.The difference of parameters between two groups were compared.The efficiency of differential diagnosis and combined diagnosis of each parameter was analyzed.The area under the receiver characteristic curve(AUC)for each parameter were compared.Results There were statistical differences in short diameter,margin and enhancement homogeneity between the two groups(t/x2=-7.575,30.971,20.913,all P＜0.001).In the benign lymph nodes group,all spectral parameters in the arterial phase(AP)were lower than those in malignant lymph nodes,while the parameters in the venous phase(VP)were higher(t=-10.723-12.610,all P＜0.001).Among the three conventional features,the AUC of short diameter was the highest(0.749).Compared with the AUC values of ICAP and ZeffVP,the AUC values of short diameter and quantitative parameters had no statistical difference(P＞0.05),but were lower than those of other spectral parameters.Among the spectral parameters,the AUC value of nICVP was the highest(0.925).The sensitivity and specificity of the spectral parameters were higher than those of conventional features.The diagnostic efficacy of the multi-parameter combined model was superior to that of the univariate model.The AUC value of the combined model with conventional features was 0.815.Among the combined model based on CT spectral parameters,the diagnostic efficacy of model combined with the parameters of arteriovenous phase was the highest(AUC=0.993).Conclusion The quantitative parameters of dual-phase enhancement derived from dual-layer spectral detector CT can effectively evaluate the characteristics of gastric cancer regional lymph nodes,and the diagnostic efficiency is higher than the conventional characteristics of lymph nodes.The multi-parameter combined model can improve the diagnostic efficiency.

Objective To discover the host factor interacting with severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)papain-like protease(PLpro)and explore the potential mechanism.Methods The second-generation proximity-dependent biotin identification(BioID2)approach combined with mass spectrometry analysis was used to search for the potential host factors.Immunofluorescence and co-immunoprecipitation(Co-IP)assay were used to verify the interactions between DEAD-box helicase 3(DDX3)and PLpro.The influence of PLpro on DDX3-inhibitor of kappa B kinase ε(IKKε)-TANK-binding kinase 1(TBK1)and DDX3-mitochondrial antiviral signaling protein(MAVS)complexes was also investigated by Co-IP.The effect of PLpro on interferon-β(IFN-β)immune pathway and the protease activity on substrates were studied via luciferase activity assay.Results DDX3 could co-locate and interact with PLpro intracellularly.PLpro might possibly inhibit both the formation of DDX3-MAVS complex and the interactions between DDX3-IKK-ε-TBK1.PLpro could negatively regulate type Ⅰ interferon pathway.Overexpression of DDX3 could lead to a significant increase in the cleavage activity of PLpro/PLP-TM that might be significantly decreased in case of inventions with DDX3 expressions.Conclusion DDX3 may be one of the host factors that interact with SARS-CoV-2 PLpro.PLpro negatively regulates IFN-β immune pathway induced by DDX3,which may provide a favorable immune environment for virus replication.

Objective:To investigate the application value of magnetic resonance imaging(MRI) in evaluating the efficacy of anti-PD-1 combined with neoadjuvant therapy for microsatellite stability (MSS)/proficient mismatch repair (pMMR) locally advanced rectal cancer (LARC).Methods:The prospective single-arm phase Ⅱ study was conducted. The clinicopathological data of 37 patients with MSS/pMMR LARC who were admitted to Beijing Friendship Hospital of Capital Medical University from April 2021 to September 2022 were collected. All patients underwent anti-PD-1 combined with neoadjuvant therapy and radical total mesorectal excision. Observation indicators: (1) enrolled pati-ents; (2) MRI and pathological examination; (3) concordance analysis of MRI examination reading; (4) evaluation of MRI examination. Measurement data with normal distribution were represented as Mean± SD. Count data were expressed as absolute numbers or percentages. Linear weighted κ value was used to evaluate the concordance of radiologist assessment. Sensitivity, negative predictive value, accuracy, overstaging rate and understaging rate were used to evaluate the predictive value. Results:(1) Enrolled patients. A total of 37 eligible patients were screened out, including 21 males and 16 females, aged (61±11)years. MRI examination was performed before and after combined therapy, and pathological examination was performed after radical resection. (2) MRI and pathological examination of patients. Among the 37 patients, MRI before combined therapy showed 0, 0, 5, 24 and 8 cases in stage T0, T1, T2, T3 and T4, 10, 17 and 10 cases in stage N0, N1 and N2, 28 and 9 cases of positive and negative extramural vascular invasion (EMVI), 4 and 33 cases of positive and negative mesorectal fascia (MRF), respectively. MRI examination after combined therapy showed 15, 4, 7, 10 and 1 cases in stage T0, T1, T2, T3 and T4, 34, 2 and 1 cases in stage N0, N1 and N2, 9 and 28 cases of positive and negative EMVI, 1 and 36 cases of positive and negative MRF. There were 16, 13, 8 and 0 cases of tumor regression grading (TRG) 0, 1, 2 and 3, respectively. Postoperative pathological examination showed 18, 4, 3, 11, 1 cases in stage T0, T1, T2, T3, T4, 33, 3, 1 cases in stage N0, N1, N2, positive and negative EMVI and unknown data in 1, 35, 1 cases, positive and negative circumferential margin in 0 and 37 cases, grade 0, grade 1, grade 2, grade 3 of American Joint Committee on Cancer TRG in 18, 9, 8, 2 cases, respectively. Pathological complete response rate was 48.6%(18/37) and approximate pathological complete response rate was 24.3%(9/37). (3)Concordance analysis of MRI examination reading. The κ value of T staging and N staging on MRI before combined therapy was 0.839 ( P<0.05) and 0.838 ( P<0.05), respectively. The κ value of T staging and N staging on MRI after combined therapy was 0.531 ( P<0.05) and 0.846 ( P<0.05), respectively. The κ value of EMVI and MRF was 0.708 ( P<0.05) and 0.680 ( P<0.05) before combined therapy, and they were 0.561 ( P<0.05) and 1.000 ( P<0.05) after combined therapy, respectively. The κ value of TRG 3-round reading for TRG was 0.448 ( P<0.05). (4) Evaluation of MRI examination. ① MRI evaluation of T and N staging. The accuracy of MRI examination after combined therapy for distinguishing stage T0 was 75.7%[28/37, 95% confidence interval ( CI) as 62.2%-89.2%], the understaging rate was 8.1%(3/37, 95% CI as 0-18.9%), the overstaging rate was 16.2%(6/37, 95% CI as 5.4%-29.7%). The accuracy of MRI examination for distinguishing stage T0-T2 was 86.5%(32/37, 95% CI as 73.0%-97.3%), its understaging rate and overstaging rate were 8.1%(3/37, 95% CI as 0-18.9%) and 5.4% (2/37, 95% CI as 0-13.5%), respectively. The accuracy of MRI examination for distinguishing N staging was 91.9%(34/37, 95% CI was 81.1%-100.0%), its understaging rate and overstaging rate were 5.4%(2/37, 95% CI as 0-13.5%) and 2.7%(1/37, 95% CI as 0-8.1%), respectively. Among 18 patients in pathological stage T0, the overstaging rate of MRI was 33.3%(6/18). All the 4 patients in pathological stage T1 and 3 pati-ents in pathological stage T2 had correct diagnosis. There were 3 cases with understaging among 12 patients in pathological stage T3-T4. Among the 37 patients in pathological stage N0-N2, 34 cases had correct diagnosis, 1 case was overstaged as stage N1 due to a round mesorectal lymph node with short diameter as 6 mm, and 2 cases were diagnosed as stage N0 due to the small lymph nodes with the maximum short diameter as 3 mm. ② MRI evaluation of EMVI and MRF. The accuracy, sensitivity and negative predictive value of MRI for evaluating EMVI were 86.5%(32/37, 95% CI as 75.0%-97.2%), 100.0% and 100.0%, respectively, and the overestimation rate of EMVI was 13.9%(5/36, 95% CI as 2.8%-25.0%), and no underestimation occurred. Of 35 pathologically negative EMVI patients, a rate of 14.3%(5/35) of patients were positive on MRI. The main reason for overestaging was that thickened fibrous tissue outside the rectal wall was mistaken for vascular invasion. The accuracy of MRI for evaluating MRF was 97.3%(36/37, 95% CI as 91.9%-100.0%), and 1 case (1/37, 2.7%, 95% CI as 0-8.1%) was overestimated as positive MRF due to misdiagnosis of pararectal MRF lymph nodes. The negative predictive value of MRI for assessing MRF was 100.0%. ③ MRI evaluation of TRG. The accuracy, understaging and overstaging rates of MRI for evaluating pathological TRG 0 were 78.4%(29/37, 95% CI as 64.9%-91.9%), 8.1%(3/37, 95% CI as 0-18.9%), 13.5%(5/37, 95% CI as 5.4%-27.0%), respectively. The accuracy, understaging and overstaging rates of MRI for evaluating pathological TRG 0-1 were 89.2%(33/37, 95% CI as 78.4%-97.3%), 8.1%(3/37, 95% CI as 0-18.9%), 2.7%(1/37, 95% CI as 0-8.1%), respectively. Of the 18 patients with pathologic complete response, 5 cases were diagnosed as pathological TRG 1 and 13 cases as pathological TRG 0. One near-pCR patient was assessed as pathological TRG 2. Two patients with pathological TRG 3 were incorrectly diagnosed on MRI. Conclusions:Anti-PD-1 combined with neoadjuvant therapy can downstage the LARC pati-ents with MSS/pMMR. MRI is effective in predicting T staging, N staging, EMVI, MRF and TRG. However, overstaging should be prevented.