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.

In this work, starting from 4-hydroxycoumarin, three series of 22 coumarin derivatives, among which 8 have not been reported in the literature, were synthesized and their in vitro anti-inflammatory activities and mechanisms of action were preliminarily investigated using mouse macrophage model. The results showed that most of the derivatives could significantly inhibit the production of pro-inflammatory factor NO, with compounds 2e, 2f, 2g, 2h, 2i, 2j, 4e, and 4f showing better anti-inflammatory activity than the positive control drug dexamethasone. Further experiments showed that compounds 2h and 4f significantly inhibited the production of pro-inflammatory factors IL-6, TNF-α and IL-1β in RAW264.7 macrophages, and could, therefore, be used as lead compounds for further studies.

The prefrontal cortex and hippocampus may support sequential working memory beyond episodic memory and spatial navigation. This stereoelectroencephalography (SEEG) study investigated how the dorsolateral prefrontal cortex (DLPFC) interacts with the hippocampus in the online processing of sequential information. Twenty patients with epilepsy (eight women, age 27.6 ± 8.2 years) completed a line ordering task with SEEG recordings over the DLPFC and the hippocampus. Participants showed longer thinking times and more recall errors when asked to arrange random lines clockwise (random trials) than to maintain ordered lines (ordered trials) before recalling the orientation of a particular line. First, the ordering-related increase in thinking time and recall error was associated with a transient theta power increase in the hippocampus and a sustained theta power increase in the DLPFC (3-10 Hz). In particular, the hippocampal theta power increase correlated with the memory precision of line orientation. Second, theta phase coherences between the DLPFC and hippocampus were enhanced for ordering, especially for more precisely memorized lines. Third, the theta band DLPFC → hippocampus influence was selectively enhanced for ordering, especially for more precisely memorized lines. This study suggests that theta oscillations may support DLPFC-hippocampal interactions in the online processing of sequential information.
Adult ; Female ; Humans ; Young Adult ; Epilepsy ; Hippocampus ; Memory, Short-Term ; Mental Recall ; Prefrontal Cortex ; Theta Rhythm ; Male

Objective To investigate the inhibitory effects of magnesium citrate(MgCit)on oxidative stress in chronic renal failure(CRF).Methods SD rats were divided into CRF model group,MgCit groups(375 and 750 mg/kg),normal control group,and MgCit control group(750 mg/kg).The morphology of mitochondria in thoracic artery vascular smooth muscle cells(VSMCs)was observed by transmission electron microscopy.The content of superoxide dismutase(SOD)and malonaldehyde(MDA)in rat aorta and plasma was detected by the kit.The VSMCs were divided into normal control group,CRF model group,and MgCit groups(1.5 and 3 mmol/L).The levels of superoxide anion(DHE)and apoptosis were quantitatively detected by flow cytometry.Results Compared with the control groups,the mitochondria were swollen and the cristae fractured or disappeared in the model group;MgCit intervention could reduce mitochondrial swelling,but not cristae fracture.In the model group,SOD level in aorta and plasma decreased(P＜0.05)while MDA level increased(P＜0.05).MgCit intervention could increase SOD in aorta and plasma,but decrease MDA level(P＜0.05).In the CRF environment,the DHE content of VSMCs and apoptosis in CRF model group increased(P＜0.05).MgCit intervention could decrease DHE content and inhibit apoptosis(P＜0.05).Conclusion MgCit inhibits oxidative stress levels in vivo and in vitro in CRF.

To investigate the initial experience of coated metal ureteral stent(CMUS)for treatment of pelvic lipomatosis induced hydronephrosis(PLH).The clinical and follow-up data of 8 patients who were diagnosed as PLH treated with CMUS in Peking University People's Hospital from August 2018 to February 2021 were retrospectively analyzed.Inclusion criteria included:Imaging evidence of excessive adipose tissue around the bladder in the pelvic cavity,bladder elevation in an"inverted pear shape",and bladder wall thickening;Cystoscopy indicated follicular hyperplasia of bladder mucosa and biopsy pathology indicated glandular cystitis;Unilateral or bilateral hydronephrosis and ureteromegaly.Exclusion criteria included:Ureteral atresia;Recurrent obstruction of the bladder outlet.Preoperative baseline data included age,gender,serum creatinine,pelvis width and ureteric stent symptoms questionnaire(USSQ)score.Intraoperative data included the location and length of ureteral stenosis observed by retrograde urography.Postoperative follow-up data included serum creatinine,pelvis width,and USSQ score.In the study,8 patients(11 sides)with PLH were all male,with an average age of(38.7±8.6)years.Uni-lateral hydronephrosis was found in 5 cases and bilateral hydronephrosis in 3 cases.Preoperative mean serum creatinine was(90.0±10.3)μmol/L,and the mean renal pelvis width was(3.0±1.5)cm.The lower ureteral stricture was found in all cases,and the mean stricture length was(1.9±0.9)cm.Before operation,3 patients had ureteral Double-J stents,with USSQ scores of 97.0,68.0 and 100.0,respectively.Five patients underwent retrograde CMUS stenting,and 3 patients retrograde and antegrade.At the last follow-up,the average serum creatinine was(82.0±11.1)μmol/L and the mean renal pel-vis width was(1.9±0.5)cm,which were significantly lower than those before operation(t=3.12,P=0.02;t=3.23,P=0.02).In the 3 patients with Double-J stent before surgery,the USSQ scores were 87.0,62.0 and 89.0,respectively,which were significantly improved after CMUS stenting.The average follow-up time was(10.0±6.3)months.During the follow-up,1 patient developed CMUS re-lated symptoms,and no stent-associated infection and stent encrustation were found.In one case,the stent migrated to the bladder 3 months after operation,and the hydronephrosis disappeared after 3 months follow-up.CMUS stenting for treatment of PLH has certain efficacy and safety,which can explore a new therapeutic method for the long-term treatment of PLH.

Objective To explore the impact of clinical treatment decisions on the long-term survival of different molecular subtypes of locally advanced breast cancer(LABC),and to promote the development of more effective and individualized treatment regimens for LABC.Methods The cases of LABC diagnosed by pathology from 2010 to 2015 were searched in the database.Breast cancer-specific survival(BCSS)and overall survival(OS)were estimated by plotting Kaplan-Meier curves.The log rank test(Mantel-Cox)was used to analyze the difference between the groups,and the benefit population of LABC was determined after for age,TNM stage,grade,treatment methods.Results The 5-year OS and BCSS were 77.43％and 84.34％in breast-conserving,and 68.03％and 76.90％in mastectomy,respectively.The 5-year OS and BCSS of Luminal A LABC were 79.91％and 87.23％in breast-conserving,and 71.78％and 81.16％in mastectomy,respectively.The 5-year OS and BCSS of Luminal B LABC were 79.30％and 83.14％in breast-conserving,and were 70.37％and 76.92％in mastectomy,respectively.The 5-year OS and BCSS of triple-negative LABC were 60.77％and 68.13％in breast-conserving,and those of mastectomy were 47.13％and 55.94％,respectively.The 5-year OS and BCSS of HER2 positive were 75.42％,82.05％in breast-conserving,and were 67.05％and 75.01％in mastectomy,respectively;The 5-year OS and BCSS of triple-positive LABC were 86.12％and 91.63％in breast-conserving,and 74.54％and 82.56％in mastectomy,respectively.The 5-year OS and BCSS of well differentiated and N0 triple-positive LABC patients with chemotherapy were 88.24％and 76.91％,and those of patients without chmotherapy were 88.24％and 90.91％,respectively(BCSS:P=0.812;OS:P=0.311).Conclusion In the selective population,OS and BCSS of patients with LABC undergoing breast conserving surgery were significantly better than those of mastectomy.When OS and BCSS were compared for different molecular types and stages of LABC,breast-conserving surgery was still superior to total mastectomy.LABC could be considered for highly differentiated,N0 stage Triple positive without chemotherapy.

Objective To investigate the effect of iron on measurement of bone mineral density(BMD)by quantitative computed tomography(QCT)and to establish a correction equation to exclude the effect of iron by using R2*.Methods A total of 15 water models containing different concentrations of iron were prepared by analyzing pure anhydrous calcium chloride and 100 mg/mL iron dextran injection.Each water model was scanned by CT and MRI under the same conditions,and the CT,QCT BMD and R2*val-ues were measured.The correlation analysis was performed between iron concentration and CT value,and QCT BMD value.Simple linear regression analysis was performed between iron concentration and QCT BMD value,between QCT BMDiron and R2*.Results There was a significant positive correlation between iron concentration and CT value,and QCT BMD value(rCT value=0.994,P＜0.001,rQCT BMD=0.993,P＜0.001).The simple linear regression equation between iron concentration and QCT BMD value was established:y=2.34x+159(x:iron concentration,y:QCT BMD).The correction equation was:QCT BMDcorrection=QCT BMDmeasurement-0.093 R2*+0.434.Conclusion Under ideal conditions,iron has an effect on measurement of BMD by QCT,and iron reduces the accuracy of measure-ment of BMD by QCT.The effect of iron on measurement of BMD by QCT needs to be corrected by correction equation.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective To explore the application value of telmisartan combined with calcium dobesilate in patients with non-dipper hypertension complicated with type 2 diabetes mellitus(T2DM).Methods A total of 260 patients with non-dipper hypertension complicated with T2DM in the endocrinology department of our hospital were selected in this study from January 2021 to December 2022.All the patients were randomly divided into telmisartan group(Tel,n=110)and telmisartan+calcium dobesilate group(Tel+Cal-dob,n=150).The blood pressure level,blood pressure rhythm changes,brachial flow mediated dilatation(FMD),carotid radial pulse wave velocity(crPWV),vasomotor factors[nitric oxide(NO),endothelin-1(ET-1),vascular endothelial growth factor(VEGF)]and the incidence of adverse reactions were compared between the two groups.Results There was no significant difference in general data and biochemical indexes between the two groups(P>0.05).After 3,6 and 12 months of treatment,the FMD and NO were higher,while the dSBP,dDBP,24 hSBP,24 hDBP,nSBP,nDBP,crPWV,ET-1 and VEGF were lower than before treatment in both groups(P<0.05).After 3,6 and 12 months of treatment,the FMD and NO were higher,while dSBP,dDBP,24 hSBP,24 hDBP,nSBP,nDBP,crPWV,ET-1 and VEGF were lower in Tel+Cal-dob group than in Tel group(P<0.05).After 3,6 and 12 months of treatment,the conversion rates of dipper blood pressure were higher in Tel+Cal-dob groupthan in Tel group(P<0.05).There was no significant difference in the incidence of adverse effects between the two groups(P>0.05).Conclusion Telmisartan combined with calcium dobesilate is effective in the treatment of patients with non-dipper hypertension complicated with T2DM.