ObjectiveTo investigate the effects of Hei Xiaoyaosan on neuroinflammation in APP/PS1 mice and decipher the mechanism based on the C-X3-C chemokine ligand 1 （CX3CL1）-CX3CL1 receptor 1 （CX3CR1） signaling axis. MethodsSixty 16-week-old male APP/PS1 mice were selected and acclimatized for one week， and they were then randomly allocated into a model group， a CX3CL1 group （bilateral hippocampal injection of CX3CL1 at 0.5 g·L^-1）， and high-， medium-， and low-dose （22.10， 11.05， and 5.53 g·kg^-1， respectively） Hei Xiaoyaosan groups， with 12 mice in each group. Twelve age-matched male C57BL/6J mice served as the blank group （bilateral hippocampal injection of an equal volume of PBS）. The high-， medium-， and low-dose Hei Xiaoyaosan groups received corresponding drugs via gavage， while the blank group received an equal volume of normal saline， with an intervention period of 90 days. Morris water maze was used to assess learning and memory abilities. Nissl staining was performed to observe the pathological changes in neurons of the hippocampal CA1 region. Immunohistochemistry was adopted to detect amyloid-β_1-42 （Aβ_1-42） deposition in the hippocampal CA1 region. The immunofluorescence assay was employed to detect the expression of M1 and M2 microglial markers， including cluster of differentiation 86 （CD86）/ionized calcium-binding adapter molecule 1 （Iba-1） and arginase-1 （Arg1）/Iba1. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of interleukin-8 （IL-8） and interleukin-13 （IL-13） in the hippocampal tissue. Western blot was employed to determine the protein levels of CX3CL1， CX3CR1， CREB-binding protein （CBP）， cyclic AMP response element-binding protein （CREB）， phosphorylated （p）-CREB， and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue. ResultsCompared with the blank group， the model group exhibited prolonged escape latency on day 5 and a reduced swimming distance in the target quadrant （P<0.01）， disarrangement of hippocampal neurons， with a reduced number of cells and uneven Nissl body staining， increased CD86/Iba1 expression， decreased Arg1/Iba1 expression （P<0.01）， enhanced Aβ expression （P<0.01）， an elevated IL-8 level and a declined IL-13 level （P<0.01）， and downregulated protein levels of CX3CL1， CX3CR1， CBP， p-CREB， and BDNF （P<0.01）. Compared with the model group， all treatment groups showed shortened escape latency on day 5 and an increased swimming distance in the target quadrant （P<0.05， P<0.01）， regular arrangement of neurons with an increased number and increased Nissl bodies， reduced CD86/Iba1 expression， increased Arg1/Iba1 and decreased Aβ expression （P<0.01）， and a declined IL-8 level and an elevated IL-13 level （P<0.05， P<0.01）. In the CX3CL1 group and the high- and medium-dose Hei Xiaoyaosan groups， the relative expression levels of CX3CL1， CX3CR1， CBP， and p-CREB were upregulated （P<0.01）. In the low-dose Hei Xiaoyaosan group， the relative expression levels of CX3CL1， CX3CR1， CBP， p-CREB/CREB， and BDNF were upregulated （P<0.05， P<0.01）. ConclusionHei Xiaoyaosan can improve learning and cognitive abilities in APP/PS1 mice. Specifically， it may regulate the CX3CL1/CX3CR1 signaling axis to activate the CREB/BDNF signaling pathway for the subsequent release of BDNF， modulation of microglial polarization， reduction of inflammatory cytokine levels， and attenuation of Aβ deposition.

Objective:To examine the role of intestinal macrophages and the mechanism by which they produce reactive oxygen species (ROS) in abdominal pain induced by food antigens in mice with visceral hypersensitivity.Methods:Mouse models of visceral hypersensitivity were established by subjecting animals to acute cold restraint stress (ACRS) or acetic acid enema (AAE). Visceral sensitivity was evaluated using food antigen ovalbumin (OVA)-induced responses and rectal reflex measurements following ROS scavenging. The activity of intestinal macrophages was assessed using flow cytometry. In vitro enzyme immunoassays and in vivo imaging techniques were employed to quantify ROS levels. Furthermore, the influence of OVA on ROS levels following intestinal macrophage depletion was investigated. Cell culture experiments were conducted to investigate the effects of OVA on intestinal macrophage function and ROS production.Results:The two visceral hypersensitivity mouse models exhibited a significantly lower pain threshold compared to the control group. OVA-induced visceral hypersensitivity mice demonstrated enhanced visceral motor responses (VMRs), with an increase in abdominal ROS levels (ACRS vs. control: 62.00±7.68 vs. 19.80±2.39, P<0.001; AAE vs. control: 461.80±17.25 vs. 19.80±2.39, P<0.001). When ROS were cleared from the abdominal cavity of mice, VMRs were restored to normal levels (AAE vs. AAE+ROS: 83.50±8.72 vs. 71.66±2.67, P=0.010). In this mouse model, intestinal macrophages could be classified into CD45 Med and CD45 High subtypes based on the level of CD45 expression. In the AAE group, the expression of CD45 Med macrophages in the intestinal tract decreased (AAE vs. control: 0.121±0.026 vs. 0.194±0.021, P=0.007), whereas the expression of CD45 High macrophages increased (AAE vs. control: 0.249±0.087 vs. 0.018±0.003, P=0.027). Compared with the control group, the expression of CD11b in both types of macrophages increased significantly (CD45 Med vs. control: 39 547.00±4 422.59 vs. 4 055.67±506.05, P<0.05; CD45 High vs. control: 18 960.00±1 197.84 vs. 3 147.50±286.38, P=0.008), while the expression of F4/80 decreased (CD45 Med vs. control: 6 141.67±750.06 vs. 10 544.33±974.92, P=0.008; CD45 High vs. control: 1 291.50±119.50 vs. 4 007.50±327.39, P<0.001). These findings suggest that the activity of intestinal macrophages in visceral hypersensitivity mice is altered following OVA induction. By injecting different populations of macrophages into the peritoneal cavity of mice, it was found that compared to the AAE group, the injection of CD45 High macrophages significantly increased the VMR in mice (AAE vs. AAE CD45 High: 83.50±8.72 vs. 114.38±7.15, P<0.001), and aggravated the severity of diarrhea significantly. In vitro experiments revealed that food antigens could directly induce ROS production in macrophages. Compared with the control group, both the ACRS and AAE groups of mice exhibited significant diarrhea symptoms. In contrast, the severity of diarrhea in the Macrophages exhaust+ACRS and Macrophages exhaust+AAE groups was substantially reduced, with a significantly shortened recovery period. Additionally, compared with the AAE group, the degree of diarrhea in the AAE+ROSS group was alleviated. Conclusions:Food antigens may act on intestinal macrophages, inducing abdominal pain and diarrhea in visceral hypersensitive mice via the ROS pathway. CD45 High macrophages may play a pivotal role in this process.

Objective:To explore the correlation between the oxygenation index and the monitored parameters of lung injury view in ventilator,so as to provide a basis for monitoring the change of oxygenation index by the parameters of lung injury view.Methods:A total of 28 patients who received mechanical ventilation treatment and admitted to respiratory department of the First Affiliated Hospital with Nanjing Medical University from May 14 to September 30,2024 were selected.The monitored parameters of lung injury views of them during mechanical ventilation treatment with invasive ventilators were collected,including platform pressure(Pplat),driving pressure(ΔP),mechanical energy(Emech),ratio of tidal volume to ideal body weight(TVe/IBW),etc..Then,the data of oxygenation index were obtained.Finally,135 valid data were screened out.The 84 pieces of data with oxygenation index≤300mmHg were included in low oxygen group,and 51 data with oxygenation index>300mmHg were included in normal group.The correlations between oxygenation index and Pplat,ΔP,Emech,TVe/IBW were conducted by pairwise analysis.Results:In the low oxygen group,the oxygenation index was[(196.302±74.522)mmHg]significantly negative correlation with Emech[(12.686±5.401)J/min](ρ=-0.425,P<0.05),but not was significant correlation with Pplat,ΔP,and TVe/IBW(P>0.05).In the normal group,there were not significant correlations between the oxygenation index and Pplat,ΔP,Emech and TVe/IBW(P>0.05).There was a significant negative correlation between Emech and rank of oxygenation index(β=-0.389,P<0.05)in the low oxygen group.Conclusion:The visualization function of the Emech of the monitored parameters in lung injury view of ventilator can provide help for monitoring the changes of oxygenation index of patients in the low oxygen group,and can improve the oxygenation of patients by optimizing mechanical energy.However,it is necessary to balance the contradiction between ventilation intensity and protection for lung.

Objective To explore the effect of young plasma intraperitoneal injection on the fertility and ovarian function of aging mice and analyze its potential molecular mechanism.Methods Fifty-four-week-old female C57BL/6 mice and 8-week-old male C57BL/6 mice were selected.Among them,the female mice were randomly divided into three groups:the young plasma group,the aging plasma group and the normal saline group.The young plasma group and the aging plasma group received intraperitoneal injection of plasma from young(25-29 years old)and elderly(45-49 years old)female donors,respectively.Each injection was 500 μL,administered every other day for 2 weeks.The saline group received an equal volume of saline.After the last injection,mating experiments were conducted to evaluate fertility.Ovarian histopathological changes were observed by HE staining.Oocytes and fertilized eggs were collected after superovulation and cultured in vitro to assess oocyte quality and embryo developmental potential.Transcriptomic analysis of ovarian tissue was performed,followed by KEGG and GO enrichment analysis.Results Compared with the normal saline group and the aging plasma group,the number of offspring increased in the young plasma group,which reflected higher extrusion rate of first polar body(PB1),decreased fragmentation rate of oocytes and increased conversion rate of two-cell embryos and increased formation rate of blastocysts.There were no significant differences in these indicators between the aging plasma group and the normal saline group.Transcriptomic sequencing revealed that the differentially expressed genes in ovarian tissue of the young plasma group were mainly involved in steroid biosynthesis and metabolic pathways.Among them,the expression level of steroid sulfatase protein was significantly upregulated.Conclusion Systemic infusion of young plasma enhances the reproductive potential of aging ovaries in elderly mice.The sulfated steroid metabolites in plasma may be key substances in restoring ovarian function and delaying the process of ovarian aging.

BACKGROUND:The re-injury rate of the anterior cruciate ligament continues to be high and the unclear relationship between neuromuscular function and biomechanical risk factors may be one of the reasons for poor injury prevention and rehabilitation.OBJECTIVE:To evaluate the biomechanics and neuromuscular function characteristics of the knee joint during landing movements after anterior cruciate ligament reconstruction,and to further explore the effects of muscle strength,proprioception,and dynamic postural control on the risk indicators of anterior cruciate ligament injury during landing maneuver.METHODS:Twenty-six male anterior cruciate ligament reconstruction patients and 26 healthy control males at the age of 18-35 years were recruited and randomized to undergo joint kinesthesia test,Y-balance test,and isometric muscle strength tests.Kinematic and kinetic data of the knee joints during single-legged jump landing tasks were collected using an infrared motion capture system and force plates.RESULTS AND CONCLUSION:(1)Compared with the healthy control group,patients after anterior cruciate ligament reconstruction demonstrated higher knee valgus angle(P=0.021),lower hamstring muscle strength(P＜0.001),lower quadriceps muscle strength(P＜0.001)and Y-balance anterior reach distance(P＜0.001),and worse knee flexion kinesthesia(P＜0.001)and extension kinesthesia(P=0.001).(2)The predictor variables of knee extension moment were quadriceps strength and knee flexion kinesthesia(R2=0.298,P=0.007).The predictor variable of knee varus and valgus angle was hamstring strength(R2=0.117,P=0.048).The predictor variable of knee internal and external rotation angle was the hamstring-to-quadriceps peak torque ratio(R2=0.134,P=0.037).(3)The results showed that after anterior cruciate ligament reconstruction,patients still had abnormal biomechanical action patterns and neuromuscular function defects in the frontal plane of the knee joint,and elevating the muscle strength of the hamstrings,avoiding excessive quadriceps muscle strength and enhancing the proprioception of the knee joint were helpful to improve the biomechanical patterns of the sagittal plane,frontal plane and horizontal plane of the knee joint and reduce the risk of anterior cruciate ligament injury during landing maneuvers.

Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future, aiming to provide valuable insights and references for the continued advancement of peptide-based drugs.
Humans ; Peptides/pharmacology* ; Animals ; Neoplasms/drug therapy* ; Drug Discovery ; Neurodegenerative Diseases/drug therapy* ; Diabetes Mellitus/drug therapy*

Objective:To explore more objective detection method for the performance of diagnostic equipment with ultrasound,so as to demonstrate that the subjectivity of the interpretation criteria will affect the results of resolution parameters of detection performance of ultrasonic equipment.Methods:A total of 77 conventional probes of 33 ultrasound equipment of Jiangsu Provincial Hospital were collected and sorted out.The resolution parameters of their performance were tested twice from 2022 to 2023 by the technical personnel of our institute and the tester of Jiangsu Institute of Metrology.The data was described by using the quartiles method.The resolution parameters of performances of ultrasound equipment and probes were paired to conduct Wilcoxon rank sum test,so as to compare the differences in same institute between different years,and in same year between different institute in testing the resolution parameters of performances of ultrasound equipment and probes.Results:For linear array probes,as long as the performance was tested in accordance with the standard method,there was no statistically significant difference in the resolution parameters measured between different institutes and between different times(P>0.05).For the convex array probe,in 2023,the lateral resolution[2(2,2)]of the 70mm target group,and the axial and lateral resolutions[1(1,1)and 3(3,3.25)]of the 120mm target group of our institute were different with the lateral resolution[2(1,2)]of the 70mm target group,and the axial and lateral resolutions[2(2,3)and 2(2,3)]of the 120mm target group of Jiangsu Institute of Metrology,and the differences of them between our institute and Jiangsu Institute of Metrology were significant(Z=-2.887,-2.53,-3.69,P<0.05),respectively.In our institute,the axial and lateral resolutions[1(1,2)and 2.5(2,3)]of the 70mm target group,and the axial resolution[1(1,2)]of the 120mm target group in 2022 were different with the axial and lateral resolutions[1(1,1)and 2(2,2)]of the 70mm target group,and the axial resolution[1(1,1)]of the 120mm target group in 2023,and the differences of them between two years were significant(Z=-3.317,-3.419,-2.982,P<0.05).In Jiangsu Institute of Metrology,the lateral resolutions of the 70mm target group,and the axial resolution[1(1,1)]of the 120mm target group in 2022 year were different with those in 2023 year,and the differences of them were significant(Z=-2.333,-3.051,P<0.05),respectively.Conclusion:The interpretation for lateral resolution of convex array probe in target group with high depth,the difference of subjective interpretation criteria will cause the essential difference of final results.This paper suggested that the key image should be retained when the resolution of the image of target group with high depth of the convex array probe is interpreted.At the later stage,artificial intelligence(AI)-assisted quality control can also be introduced to conduct objective interpretation by computers.

Cerebral ischemia/reperfusion injury(CIRI)is a pathophysiological process affecting the prognosis of patients with acute ischemic stroke(AIS).Its mechanism is complex and remains unclear.Long non-coding RNA(LncRNA)are a class of non-coding RNA(ncRNA).Early studies of LncRNA focused on their relationship with tumor-related diseases,but recent studies have found that they are also closely related to the pathological process of CIRI.LncRNA participate in the damage and repair processes of CIRI by affecting oxidative stress,autophagy,and apoptosis of the nervous system,as well as the inflammatory response and other mechanisms.They can regulate the progression of CIRI in a positive or negative way,and they play an important role in the related signaling pathways.This review focuses on the mechanisms bv which LncRNA regulate CIRI.

The presence of magnetic fields in a magnetic resonance accelerator (MR-linac) can affect the reference dosimetry, and thus the existing Code of Practices (CoPs) are inadequate for MR-linac. In this article, the characteristics of adsorbed dose to water and ionization chamber response in the presence of magnetic fields were introduced and a formalism for reference dosimetry in MR-linac was developed based on the existing CoPs, aiming to provide reference for dosimetric quality control and research work of MR-linac in China.

Objective:To examine the role of intestinal macrophages and the mechanism by which they produce reactive oxygen species (ROS) in abdominal pain induced by food antigens in mice with visceral hypersensitivity.Methods:Mouse models of visceral hypersensitivity were established by subjecting animals to acute cold restraint stress (ACRS) or acetic acid enema (AAE). Visceral sensitivity was evaluated using food antigen ovalbumin (OVA)-induced responses and rectal reflex measurements following ROS scavenging. The activity of intestinal macrophages was assessed using flow cytometry. In vitro enzyme immunoassays and in vivo imaging techniques were employed to quantify ROS levels. Furthermore, the influence of OVA on ROS levels following intestinal macrophage depletion was investigated. Cell culture experiments were conducted to investigate the effects of OVA on intestinal macrophage function and ROS production.Results:The two visceral hypersensitivity mouse models exhibited a significantly lower pain threshold compared to the control group. OVA-induced visceral hypersensitivity mice demonstrated enhanced visceral motor responses (VMRs), with an increase in abdominal ROS levels (ACRS vs. control: 62.00±7.68 vs. 19.80±2.39, P<0.001; AAE vs. control: 461.80±17.25 vs. 19.80±2.39, P<0.001). When ROS were cleared from the abdominal cavity of mice, VMRs were restored to normal levels (AAE vs. AAE+ROS: 83.50±8.72 vs. 71.66±2.67, P=0.010). In this mouse model, intestinal macrophages could be classified into CD45 Med and CD45 High subtypes based on the level of CD45 expression. In the AAE group, the expression of CD45 Med macrophages in the intestinal tract decreased (AAE vs. control: 0.121±0.026 vs. 0.194±0.021, P=0.007), whereas the expression of CD45 High macrophages increased (AAE vs. control: 0.249±0.087 vs. 0.018±0.003, P=0.027). Compared with the control group, the expression of CD11b in both types of macrophages increased significantly (CD45 Med vs. control: 39 547.00±4 422.59 vs. 4 055.67±506.05, P<0.05; CD45 High vs. control: 18 960.00±1 197.84 vs. 3 147.50±286.38, P=0.008), while the expression of F4/80 decreased (CD45 Med vs. control: 6 141.67±750.06 vs. 10 544.33±974.92, P=0.008; CD45 High vs. control: 1 291.50±119.50 vs. 4 007.50±327.39, P<0.001). These findings suggest that the activity of intestinal macrophages in visceral hypersensitivity mice is altered following OVA induction. By injecting different populations of macrophages into the peritoneal cavity of mice, it was found that compared to the AAE group, the injection of CD45 High macrophages significantly increased the VMR in mice (AAE vs. AAE CD45 High: 83.50±8.72 vs. 114.38±7.15, P<0.001), and aggravated the severity of diarrhea significantly. In vitro experiments revealed that food antigens could directly induce ROS production in macrophages. Compared with the control group, both the ACRS and AAE groups of mice exhibited significant diarrhea symptoms. In contrast, the severity of diarrhea in the Macrophages exhaust+ACRS and Macrophages exhaust+AAE groups was substantially reduced, with a significantly shortened recovery period. Additionally, compared with the AAE group, the degree of diarrhea in the AAE+ROSS group was alleviated. Conclusions:Food antigens may act on intestinal macrophages, inducing abdominal pain and diarrhea in visceral hypersensitive mice via the ROS pathway. CD45 High macrophages may play a pivotal role in this process.