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.

Objective:This study aimed to explore the performance of renal resistive index (RRI), semiquantitative power Doppler ultrasound (PDU) score, and renal venous Doppler waveform (RVDW) pattern in predicting 28-day renal dysfunction in critically ill patients and establish nomogram model.Methods:This was a prospective, observational study. Critically ill patients admitted to the emergency intensive care unit (ICU) of Cangzhou Central Hospital from January 2018 to October 2022 were included. Patients underwent renal ultrasound examination to obtain RRI, PDU score and RVDW pattern within 24 h after ICU admission. The following clinical variables were collected during the renal ultrasound examination session, including heart rate, mean arterial pressure, type and dose of vasoactive drugs, oxygen therapy parameters, and average urine volume per hour derived from a period of 6 h prior to the ultrasound examination. The data on duration of AKI and mortality were recorded on the 28th day of follow-up. Patients were divided into 28-day normal renal function group and 28-day renal dysfunction group according to 28-day renal dysfunction. 28-days of renal dysfunction was defined as failure to achieve renal function recovery within 28 days of ICU admission. The difference of each index between the two groups was compared. Associated factors for 28-day renal dysfunction were determined by univariate and multivariate COX regression analyses. A nomogram was developed based on the independently factors associated with 28-day renal dysfunction. Survival receiver operator characteristic (ROC) curves were plotted to assess diagnostic performance in predicting 28-day renal dysfunction. Delong’s test was used to compare area under the curves (AUC) between each predictor.Results:187 patients were enrolled for the final analysis: 97 with no AKI, 48 with AKI stage 1, 24 with AKI stage 2, and 18 with AKI stage 3 upon enrollment. At 28-day follow up, 16 patients had renal dysfunction and 2 required continuous renal replacement therapy (CRRT). The multivariate COX regression showed that RVDW and SCr upon enrollment were the independent risk predictors. Nomogram based on RVDW and SCr upon enrollment showed the best performance in predicting 14-day renal dysfunction (AUC = 0.918, 95% CI:0.871-0.964, P<0.05), and the AUC was statistically significantly higher than single index (all P<0.05). Nomogram also showed the best performance in predicting 28-day renal dysfunction (AUC = 0.924, 95% CI:0.865-0.983, P<0.05), and the AUC was statistically significantly higher than single index (all P<0.05) except for SCr upon enrollment. The optimal cutoff for nomogram in predicting 28-day renal dysfunction was ≤89.5 (sensitivity, 81.2%; specificity, 90.6%; Youden index, 0.719). Kaplan-Meier analysis showed that the median duration of renal dysfunction in the groups with total nomogram score >85.9 and ≤85.9 was 0 and 22 days (HR=0.220, 95% CI:0.129-0.376, P<0.001). Conclusions:SCr and RVDW pattern within 24 h from ICU admission were independent factors associated with 28-day renal dysfunction in critically ill patients. The value of the nomogram model based on these two factors in predicting 28-day renal dysfunction is superior to each single intrarenal Doppler spectrum indicator and clinical indicator.

AIM:To observe the effect of curcumin on a C57BL/6J mouse liver cancer model induced by N-ni-trosodiethylamine(DEN)combined with carbon tetrachloride(CCl4),and to explore its mechanism.METHODS:Forty young male C57BL/6J mice were intraperitoneally injected with DEN(25 mg/kg)14 d after birth and randomly divided in-to the following 4 groups at the 4th week(10 in each group):model control group and curcumin(100,200 and 400 mg/kg)groups.Ten male mice of the same age were used as normal control group.The mice in model group and curcumin groups were gavaged with 10%CCl4(5 mL/kg)twice a week from the 8th week on.At the same time,the mice in curcumin groups were gavaged with curcumin,and the mice in normal control group were gavaged with the same volume of distilled water once a day for 14 weeks.After administration,the mice were sacrificed,the liver surface was observed,and the number of tumor nodules was compared.The activity of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum was detected by an automatic biochemical instrument.The pathological changes of liver tissues were ob-served by HE staining.The mRNA expression levels of heme oxygenase-1(HO-1)and NAD(P)H-quinone oxidoreductase 1(NQO1)were detected by RT-qPCR,and the protein expression levels of HO-1,NQO1 and Ki67 were detected by Western blot and immunohistochemistry.RESULTS:Compared with normal control group,the body weight of the mice in model group was decreased significantly(P＜0.01),the liver index was increased significantly(P＜0.01),and the se-rum levels of ALT and AST were increased obviously(P＜0.01).There was no significant difference in the mRNA expres-sion levels of HO-1 and NQO1(P＞0.05),the protein levels of HO-1 and NQO1 were increased distinctly(P＜0.05),and the positive expression rate of Ki67 was increased significantly(P＜0.05).After curcumin treatment,the body weight of the mice was significantly increased(P＜0.01),the liver index was not changed(P＞0.05),and the number of tumor nodules in the liver was decreased significantly(P＜0.05 or P＜0.01).The serum level of AST was decreased significantly(P＜0.01),the mRNA and protein expression levels of HO-1 and NQO1 were decreased significantly(P＜0.05),and the posi-tive expression rate of Ki67 was decreased significantly(P＜0.05).CONCLUSION:Curcumin significantly protects against liver cancer in a C57BL/6J mouse model induced by DEN combined with CCl4,and its mechanism may be related to the inhibition of HO-1 and NQO1 expression.

ObjectiveTo explore the effect of grain-sized moxibustion at "Zhongwan （RN12）" "Tianshu （ST25）" and "Shangjuxu （ST37）" on the colon tissue of mice with ulcerative colitis （UC）， and to analyze the potential mechanism. MethodsForty C57BL/6 male mice were randomly divided into blank group， model group， moxibustion group and mesalazine group， with 10 mice in each group. In all the groups except for the blank group， UC mouse model was prepared by freely drinking 3% sodium dextran sulfate solution. After successful modeling， the moxibustion group was treated with grain-sized moxibustion at Zhongwan， Tianshu and Shangjuxu ， 3 cones per acupoint， 30 s of each cone. The mesalazine group was given 300 mg/kg of mesalazine enteric-coated tablet solution by gavage. The blank group and the model group were only fixed by grasping without any intervention. Each group was intervened once a day for 7 consecutive days. The general condition of mice in each group was observed， and the disease activity index （DAI） score was evaluated. The colon length， intestinal weight and colon mucosal injury score were detected. The contents of serum intercellular adhesion molecule-1 （ICAM-1）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） were detected by ELISA. The pathological changes of colon tissue were observed by HE staining. The mRNA and protein expressions of non-receptor tyrosine protein kinase 2 （JAK2）， signal transducer and activator of transcription 3 （STAT3） and suppressor of cytokine signaling 3 （SOCS3） in colon tissue of mice were detected by real-time fluorescence quantitative PCR and immunohistochemistry， respectively. The mean fluorescence intensity of JAK2 and SOCS3 in colon tissue of mice was detected by immunofluorescence double staining. ResultsCompared to the blank group， the mice in the model group had unclean perianal area， unformed stool， destroyed colonic mucosal morphology， shortened body weight and colon length， increased DAI score， intestinal weight index， colonic mucosal injury and pathological score， serum ICAM-1， IL-6 and TNF-α levels， increased mRNA and protein expression of JAK2 and STAT3 in colon tissue， and decreased mRNA and protein expression of SOCS3 （P＜0.01）. Compared to those in the model group， the perianal area of mice in the moxibustion group and the mesalazine group was improved， and the colonic mucosal morphology was more complete； body weight and colon length increased， while DAI score， intestinal weight index， colonic mucosal injury and pathological score， serum ICAM-1， IL-6 and TNF-α levels decreased， with decreased mRNA and protein expression of JAK2 and STAT3 in colon tissue， and increased SOCS3 mRNA and protein expression （ P＜0.01 or P＜0.05 ）. There was no significant difference in any index between the moxibustion group and the mesalazine group. ConclusionGrain-sized moxibustion at "Zhongwan"， "Tianshu" and "Shangjuxu" can improve the damage of colon mucosa in UC model mice， and the mechanism may be related to the key factors regulating JAK2 / STAT3 signaling pathway based on SOCS3.

Objective:The transjugular or transfemoral approach is used as a common method for hepatic venous pressure gradient (HVPG) measurement in current practice. This study aims to confirm the safety and effectiveness of measuring HVPG via the forearm venous approach.Methods:Prospective recruitment was conducted for patients with cirrhosis who underwent HVPG measurement via the forearm venous approach at six hospitals in China and Japan from September 2020 to December 2020. Patients' clinical baseline information and HVPG measurement data were collected. The right median cubital vein or basilic vein approach for all enrolled patients was selected. The HVPG standard process was used to measure pressure. Research data were analyzed using SPSS 22.0 statistical software. Quantitative data were used to represent medians (interquartile ranges), while qualitative data were used to represent frequency and rates. The correlation between two sets of data was analyzed using Pearson correlation analysis.Results:A total of 43 cases were enrolled in this study. Of these, 41 (95.3%) successfully underwent HVPG measurement via the forearm venous approach. None of the patients had any serious complications. The median operation time for HVPG detection via forearm vein was 18.0 minutes (12.3~38.8 minutes). This study confirmed that HVPG was positively closely related to Child-Pugh score ( r = 0.47, P = 0.002), albumin-bilirubin score ( r = 0.37, P = 0.001), Lok index ( r = 0.36, P = 0.02), liver stiffness ( r = 0.58, P = 0.01), and spleen stiffness ( r = 0.77, P = 0.01), while negatively correlated with albumin ( r = -0.42, P = 0.006). Conclusion:The results of this multi-centre retrospective study suggest that HVPG measurement via the forearm venous approach is safe and feasible.

Objective:To explore the relationship between serum levels of transforming growth factor- β1 (TGF- β1), vascular endothelial growth factor (VEGF) and tumor markers and local recurrence after breast-conserving surgery in patients with breast cancer. Methods:104 patients with breast cancer who underwent breast-conserving surgery in Xi’ an Central Hospital from Jan. 2020 to Dec. 2022 were selected and followed up for 1 year after surgery. According to the occurrence of local recurrence, they were divided into recurrence group ( n=16) and non-recurrence group ( n=88). The levels of serum TGF- β1, VEGF and tumor markers [carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA) ] were compared between the two groups of patients. Univariate and multivariate Logistic regression analyses were used to analyze the influencing factors of local recurrence after breast-conserving surgery. Receiver operating characteristic (ROC) curve was applied to analyze the predictive value of TGF- β1, VEGF, CA125 and CEA on local recurrence after breast-conserving surgery. Results:The levels of VEGF, TGF- β1, CAl25 and CEA in recurrence group [ (358.83±38.00) ng/L, (849.90±74.19) U/mL, (18.34±1.61) ng/L and (40.20±5.64) ng/mL] were higher than those of (296.05±39.57) ng/L (742.85±79.96) ng/L, (14.97±1.66) U/mL and (32.79±4.72) ng/mL in non-recurrence group (all P<0.05). Lymph node metastasis, postoperative adjuvant therapy, tumor diameter and TNM staging were independent risk factors of local recurrence after breast-conserving surgery (all P<0.05). The areas under the ROC curves (AUCs) of serum VEGF, TGF- β1, CAl25 and CEA in predicting local recurrence after breast-conserving surgery were 0.847, 0.834, 0.925 and 0.935 respectively. The AUC of CEA was the largest, with sensitivity of 85.23% and specificity of 100% (all P<0.05) . Conclusions:The levels of TGF- β1, VEGF, CAl25 and CEA in patients with local recurrence after breast-conserving surgery are increased, and their levels are more effective in predicting local recurrence after breast-conserving surgery. Local recurrence after breast-conserving surgery is also affected by lymph node metastasis, postoperative adjuvant therapy, tumor diameter and TNM staging.

Electromagnetic stimulation is an important neuromodulation technique that modulates the electrical activity of neurons and affects cortical excitability for the purpose of modulating the nervous system. The phenomenon of inverse stochastic resonance is a response mechanism of the biological nervous system to external signals and plays an important role in the signal processing of the nervous system. In this paper, a small-world neural network with electrical synaptic connections was constructed, and the inverse stochastic resonance of the small-world neural network under electromagnetic stimulation was investigated by analyzing the dynamics of the neural network. The results showed that: the Levy channel noise under electromagnetic stimulation could cause the occurrence of inverse stochastic resonance in small-world neural networks; the characteristic index and location parameter of the noise had significant effects on the intensity and duration of the inverse stochastic resonance in neural networks; the larger the probability of randomly adding edges and the number of nearest neighbor nodes in small-world networks, the more favorable the anti-stochastic resonance was; by adjusting the electromagnetic stimulation parameters, a dual regulation of the inverse stochastic resonance of the neural network can be achieved. The results of this study provide some theoretical support for exploring the regulation mechanism of electromagnetic nerve stimulation technology and the signal processing mechanism of nervous system.
Action Potentials/physiology* ; Computer Simulation ; Models, Neurological ; Stochastic Processes ; Neurons/physiology* ; Electromagnetic Phenomena

In recent years, living kidney donors is getting valuable with the increasingly needs of kidney transplantation. However, living kidney donors can receive no benefits but greater incidence and severity of pain compared to other kinds of renal surgeries. Thus, it is getting popular on how to relief the postoperative pain during perioperative period for living kidney donors. As multidisciplinary cooperation developing, preoperative predictive nursing, changed analgesia mode, modified pneumoperitoneum, and postoperative application of different kinds of analgesic drugs can further relief the postoperative pain of living kindney donors. This paper sums up different modalities of pain relief in patients undergoing live donor nephrectomy to provide reference to clinical decision of living kidney transplantation.

Weightlessness in the space environment affects astronauts' learning memory and cognitive function. Repetitive transcranial magnetic stimulation has been shown to be effective in improving cognitive dysfunction. In this study, we investigated the effects of repetitive transcranial magnetic stimulation on neural excitability and ion channels in simulated weightlessness mice from a neurophysiological perspective. Young C57 mice were divided into control, hindlimb unloading and magnetic stimulation groups. The mice in the hindlimb unloading and magnetic stimulation groups were treated with hindlimb unloading for 14 days to establish a simulated weightlessness model, while the mice in the magnetic stimulation group were subjected to 14 days of repetitive transcranial magnetic stimulation. Using isolated brain slice patch clamp experiments, the relevant indexes of action potential and the kinetic property changes of voltage-gated sodium and potassium channels were detected to analyze the excitability of neurons and their ion channel mechanisms. The results showed that the behavioral cognitive ability and neuronal excitability of the mice decreased significantly with hindlimb unloading. Repetitive transcranial magnetic stimulation could significantly improve the cognitive impairment and neuroelectrophysiological indexes of the hindlimb unloading mice. Repetitive transcranial magnetic stimulation may change the activation, inactivation and reactivation process of sodium and potassium ion channels by promoting sodium ion outflow and inhibiting potassium ion, and affect the dynamic characteristics of ion channels, so as to enhance the excitability of single neurons and improve the cognitive damage and spatial memory ability of hindlimb unloading mice.
Animals ; Mice ; Transcranial Magnetic Stimulation ; Hindlimb Suspension ; Neurons ; Cognitive Dysfunction ; Brain