Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation / 药物分析学报

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Coronary intravascular lithotripsy for calcified coronary artery calcification-systematic review of researches / 中国介入心脏病学杂志

Coronary artery calcification commonly results in reduced vascular compliance,facilitating incomplete stent expansion and in-stent restenosis after stent implantation,thereby leading to the failure of interventional treatment.Conventional approaches to managing calcified lesions are constrained by the intricate nature and properties of calcified plaques,which frequently pose challenges in their manipulation,consequently giving rise to numerous approaches complications and an elevated likelihood of adverse cardiovascular events following the procedure.Percutaneous coronary intraluminal shock wave balloon catheter angioplasty,also known as coronary intravascular lithotripsy,utilizing a balloon catheter system,demonstrates the capacity to safely and efficiently modify superficial and deep-seated calcifications,regardless of their concentric or eccentric nature.This intervention significantly enhances vascular compliance,thereby facilitating subsequent interventional therapies.Presently,coronary intravascular lithotripsy has emerged as a crucial approach in the management of coronary artery calcification.This article primarily offers a comprehensive examination of the mechanism of intravascular lithotripsy and the research pertaining to the treatment of coronary artery calcification.

Research progress of B7-H3 in tumor growth,drug resistance formation and immunotherapy / 中国免疫学杂志

B7-H3(also known as CD276)is a newly discovered immune costimulatory molecule and a member of the B7 family of immune costimulatory molecules.Since the receptor of B7-H3 has not been identified yet,the specific mechanism of its immune function and intracellular signal transmission has not yet been clarified.B7-H3 is highly expressed in many malignant tumors,which indicates that not only B7-H3 can be used as a tumor marker for many malignant tumors to assist clinical diagnosis,which can be used as an effective target for tumor targeted therapy.This review mainly introduces the history of the development of the costimulatory mole-cule B7-H3 and its possible role in the development of various malignant tumors and the development of anti-tumor drug resistance,as well as the current mainstream therapeutic approaches targeting B7-H3.

Application and evaluation study of 3D ultrasound in image guided radiotherapy for prostate cancer / 国际肿瘤学杂志

Objective:To evaluate the accuracy of 3D ultrasound calibration in image guided radiotherapy for prostate cancer by taking cone beam CT calibration as the gold standard, and to analyze the risk factors of accuracy.Methods:From December 2018 to December 2021, 51 patients with prostate cancer from the Department of Radiation Oncology, First Affiliated Hospital of Hebei North University were selected as the study subjects. They received cone beam CT calibration based on bone and 3D ultrasound calibration based on soft tissue before fraction volumetric modulated arc therapy treatment three times a week. Taking cone beam CT calibration data as the gold standard, the Bland-Altman method was used to analyze the consistency of 3D ultrasound calibration data with the former. Taking 3 mm as the allowable threshold of accuracy, the calibration accuracy of 3D ultrasound relative to cone beam CT was evaluated. Logistic regression was used to analyze the risk factors affecting the accuracy of 3D ultrasound calibration.Results:A total of 765 pairs of cone beam CT and 3D ultrasound calibration data were obtained from 51 patients in left-right, superior-inferior and anterior-posterior directions. The calibration data of 3D ultrasound and cone beam CT were (1.39±0.11) and (1.13±0.07) mm in the left-right direction, (1.98±0.20) and (1.61±0.12) mm in the superior-inferior direction, (2.68±0.48) and (1.78±0.27) mm in the anterior-posterior direction, respectively, with statistically significant differences ( t=-6.42, P<0.001; t=-7.07, P<0.001; t=-7.34, P<0.001). The analysis results of Bland-Altman showed that the consistency of calibration data of the two methods were acceptable in three directions. The number of pairs of 3D ultrasound relative to cone beam CT calibration data difference <3 mm in the three directions were 676 (88.37%) on the left-right direction, 604 (78.95%) on the superior-inferior direction, and 577 (75.42%) on the anterior-posterior direction. The factors with statistically significant differences in the left-right direction included age ( χ2=18.27, P<0.001), prostate volume ( χ2=14.55, P<0.001), Charlson comorbidity index (CCI) ( χ2=8.01, P=0.005) and field range ( χ2=11.30, P<0.001). Age ( OR=2.02, 95% CI: 1.90-3.39, P=0.010) and the field range ( OR=1.45, 95% CI: 1.18-2.55, P=0.020) were the independent risk factors affecting the accuracy of 3D ultrasound calibration in the left-right direction. The factors with statistically significant differences in the superior-inferior direction included age ( χ2=80.68, P<0.001), body mass index ( χ2=35.89, P<0.001) and field range ( χ2=40.39, P<0.001). Age ( OR=1.49, 95% CI: 1.15-2.09, P=0.021) and the field range ( OR=1.10, 95% CI: 1.01-1.90, P=0.034) were the independent risk factors affecting the accuracy of 3D ultrasound calibration in the superior-inferior direction. The factors with statistically significant differences in the anterior-posterior direction included age ( χ2=46.07, P<0.001), CCI ( χ2=47.97, P<0.001) and field range ( χ2=11.86, P=0.001). Age ( OR=1.91, 95% CI: 1.22-3.45, P=0.015) and the field range ( OR=2.89, 95% CI: 1.45-3.90, P=0.001) were the independent risk factors affecting the accuracy of 3D ultrasound calibration in the anterior-posterior direction. Conclusion:The consistency and accuracy of the calibration results of 3D ultrasound relative to cone beam CT are acceptable. It is necessary to consider the patient's age and field range to reduce the impact on accuracy before conducting 3D ultrasound calibration.

Application value of hydrogel in image guided radiotherapy for prostate cancer / 解放军医学杂志

Objective To evaluate the application value of hydrogel in image guided radiotherapy(IGRT)for prostate cancer(PCa).Methods Eighty PCa patients in the First Affiliated Hospital of Hebei North University from October 2022 to February 2023 were collected.The patients were divided into experiment group injected with hydrogel(n=33)and control group without hydrogel(n=47)by central random system allocation.The acute and advanced radiation proctitis(RP)incidence rate of the two groups were compared.Patients in experimental group were divided into RP group(n=5)and non-RP group(n=28).The independent risk factors leading to RP were analyzed by using logistic regression for PCa patients.Results In experiment group,12.1％(4/33)of the patients developed acute grade Ⅰ RP,and 3.0％(1/33)developed advanced grade Ⅰ RP.In control group,31.9％(15/47)of the patients developed acute grade Ⅰ RP,and 12.8％(6/47)developed acute grade Ⅱ RP;19.1％(9/47)of patients developed advanced grade Ⅰ RP,4.3％(2/47)developed advanced grade Ⅱ RP,and 2.1％(1/47)developed advanced grade Ⅲ RP.The incidence of acute and advanced RP in experiment group was lower than that in control group(P<0.05).The application of hydrogel effectively reduced rectal toxicity.Age,rectal volume,V70 and V78 were independent risk factors for the incidence of RP in Pca patients(P<0.05).The characteristics of hydrogel injection were not related to the incidence of RP for Pca patients.Conclusions Hydrogel can effectively reduce the rectal toxicity for Pca patients in IGRT and has little impact on the overall treatment.Hydrogel has certain clinical application and promotion value.

Application of arterial spin labeling techniques in autism spectrum disorder with or without global developmental delay / 实用放射学杂志

Objective To measure and compare the cerebral blood flow(CBF)of children with autism spectrum disorder(ASD),global developmental delay(GDD),and ASD with GDD groups via arterial spin labeling(ASL)technique,and to evaluate the diag-nostic value of CBF values.Methods ASL images of ASD,GDD,and ASD with GDD groups of children were firstly acquired,and the CBF values of frontal lobe,temporal lobe,parietal lobe,occipital lobe,striatum and thalamus region of interest(ROI)were fur-ther measured,respectively.One-way analysis of variance or Kruskal-Wallis H test was used to compare the differences in CBF values among these three groups,and the receiver operating characteristic(ROC)curve was used to analyze the efficacy of CBF values in distinguishing ASD with GDD from without GDD.Results ASD with GDD had significantly lower CBF values in the left and right frontal lobes than those with ASD or GDD alone,and the differences were statistically significant(P<0.05).The CBF values in the left and right frontal lobes effectively distinguished ASD with GDD from without GDD[area under the curve(AUC)>0.7].Conclusion ASL technique can noninvasively assess CBF in children with or without GDD,helping to understand the pathophysiology of ASD with GDD and improving diagnostic accuracy.

Three-dimensional magnetization prepared rapid acquisition gradient echo for evaluation on the corpus callosum morphological alterations in children with spastic cerebral palsy / 实用放射学杂志

Objective To analyze the morphological alterations of corpus callosum in children with spastic cerebral palsy(SCP)using three-dimensional magnetization prepared rapid acquisition gradient echo(3D-MPRAGE)technology and to investigate the correlation between morphological indexes and gross motor function.Methods Sagittal T1WI 3D-MPRAGE data was collected from 136 children with SCP(SCP group)and 132 age-and gender-matched healthy controls(HC)(HC group),and the gross motor function measure-88(GMFM-88)was applied to assess the gross motor function.Independent sample t-test was used to compare the corpus callosum surface area,volume,maximum anterior-posterior diameter,median sagittal area(total area and area of Ⅰ-Ⅴ zone)between the two groups.Partial correlation analysis was performed to calculate the correlation between morphological indexes of the corpus callosum and GMFM-88 with age as a covariate.Results Children under 3 years old,the corpus callosum surface area of the SCP group(3 914.51 mm2±1 207.97 mm2)was lower than that of the HC group(5 725.51 mm2±1 412.66 mm2).The volume of the corpus callosum(6 108.46 mm3±2 803.97 mm3)in the SCP group was lower than that of the HC group(11 297.96 mm3±4 109.02 mm3).Also,the maximum anterior-posterior diameter of the corpus callosum in the SCP group(53.40 mm±6.31 mm)was lower than that of the HC group(57.74 mm±6.04 mm)(all P<0.05).Children over 3 years old,the corpus callosum surface area of the SCP group(4 970.06 mm2±1 191.31 mm2)was lower than that of the HC group(6 372.55 mm2±1 445.59 mm2).The volume of the corpus callosum(8 330.20 mm3±2 888.20 mm3)in the SCP group was lower than that of the HC group(13 599.82 mm3±3 429.81 mm3)(all P<0.05).Partial correlation analysis showed significant correlation between corpus callosum volume,median sagittal area and gross motor score(P<0.01)with age as a covari-ate.Conclusion The 3D-MPRAGE technology can be useful for the comprehensive assessment of morphological alterations of the corpus callosum in SCP.The corpus callosum volume,and median sagittal area may become neuroimaging references for the assess-ment of motor development in cerebral palsy(CP).

Mechanical performance and collapse risk prediction of avascular necrosis of femoral head under walking movement / 中国组织工程研究

BACKGROUND:Avascular necrosis of the femoral head is a refractory orthopedic disease that seriously affects the normal life of patients.Hip preservation is recommended for young patients due to the limited prosthesis longevity and revision.Accurate prediction of the mechanical properties of the necrotic area in the early stage and then intervention is the key to hip preservation. OBJECTIVE:To establish a dynamic contact mechanics finite element model of necrotic femoral head based on human hip CT data and predict effects of both necrotic volume magnitude and its position on biomechanics of the necrotic region under walking movement. METHODS:CT data of a volunteer were collected and then geometry model of the hip was rebuilt.Finite element model of the necrotic femoral head was established using the Abaqus software.Nine different necrotic femoral models were constructed by combined both three different necrotic volume magnitudes(small,medium and big volume)and three different necrotic positions(coincided with,medium deviated with and kept away from the line of the force).The Von Mises of the necrotic region for all models were predicted under both 3 000 N static load and dynamical loads of one whole ISO walking gait cycle.The collapse risk for all models was evaluated based on collapse criterion. RESULTS AND CONCLUSION:(1)More approaching of the necrotic region to the line of force and bigger collapse volume made the maximum Von Mises increasing.This also enlarged the collapse risk of the necrotic region.(2)For different load types,walking movement increased the maximum Von Mises of the necrotic region than that of the value under static load under the same necrotic volume and location.(3)In conclusion,dynamic load would result in increasing of the maximum Von Mises of the necrotic region comparing to static load during exercise.Therefore,the risk of local collapse will increase due to greater Von Mises.However,the overall collapse risk is lower than that of static load due to the dynamic change of bearing area.This factor should be carefully considered by surgeons when they evaluate the mechanical performance of the necrotic femoral head.

Inhibitory effect of curcumin on malignant biological behavior and Wnt/β-catenin pathway of uveal melanoma cells / 中华实验眼科杂志

Objective:To explore the inhibitory effect of curcumin on the malignant biological behavior of uveal melanoma (UM) and its possible mechanism.Methods:M23 cells were cultured in curcumin medium with different concentrations (0, 20, 40 and 80 μmol/L) for 48 hours, respectively.The morphological changes of cells were observed under an inverted microscope.The cell survival rate was detected by the cell counting kit-8 (CCK-8) method.The apoptosis, colony formation, migration and invasion of cells were detected by flow cytometry, plate clone formation experiment, cell scratch experiment and Transwell assay, respectively.The relative expressions of genes related to Wnt/β-catenin pathway, c-Myc, Cyclin D1, Survivin and matrix metallo proteinase 9 ( MMP-9) mRNA in cells were detected by real-time fluorescence quantitative PCR.The relative expressions of proteins related to Wnt/β-catenin pathway, c-Myc, Cyclin D1, Survivin, MMP-9 and β-catenin, glycogen synthase kinase 3β (GSK-3β), phosphorylated GSK-3β (p-GSK-3β) and axis inhibition protein 2 (Axin2) proteins were detected by Western blot.Another 20 female BALB/c mice were selected and injected with M23 cell suspension under the subcutaneous fat pad in the left posterior abdomen to establish the in vivo M23 transplanted tumor model.The mice successfully modeled were randomly divided into model group, low-dose curcumin group, medium-dose curcumin group and high-dose curcumin group according to the random number table method, which was intraperitoneally injected with 0, 10, 20 and 40 mg/kg curcumin physiological saline solution respectively.After a continuous injection for 30 days, the subcutaneous tumor was stripped and weighed.The animal experiment process followed the 3Rs principle of animal research and was approved by the Laboratory Animal Ethics Committee of Inner Mongolia Baotou Steel Hospital (No.2021MER-023). Results:The cell survival rate, the number of colony formation, the apoptosis rate, the cell invasion rate and the cell migration rate were (100.00±0.00)%, 128.67±9.18, (1.33±0.29)%, (89.76±4.57)% and 148.33±8.18 in 0 μmol/L curcumin group, (83.78±4.59)%, 100.33±8.73, (14.53±2.04)%, (65.43±3.70)% and 125.33±7.41 in 20 μmol/L curcumin group, (66.09±3.92)%, 58.67±6.55, (27.23±3.56)%, (34.83±2.19)% and 73.67±6.34 in 40 μmol/L curcumin group, and (47.16±3.63)%, 31.67±4.92, (44.73±4.36)%, (18.82±1.99)% and 45.67±5.31 in 80 μmol/L curcumin group.There were statistically significant differences in the survival rate, colony formation number, cell apoptosis rate, migration rate and invasion rate of M23 cells among the four groups ( F=125.321, 97.941, 72.516, 277.097, 139.006; all at P<0.001). With the increase of curcumin concentration, the cell survival rate, colony formation number, cell migration rate and cell invasion number decreased obviously, and the cell apoptosis rate increased obviously, and the pairwise comparisons showed significant differences (all at P<0.05). With the increase of curcumin concentration, the relative expression levels of c-Myc, Cyclin D1, Survivin, MMP-9 mRNA and proteins, β-catenin and p-GSK-3β proteins decreased significantly, while the relative expression level of Axin2 protein increased significantly, showing significant differences in pairwise comparisons (all at P<0.05). The tumor tissue weight of mice decreased with the increase of curcumin dosage, and the pairwise comparisons were statistically significant (all at P<0.05). Conclusions:Curcumin can inhibit the proliferation, migration, invasion and other malignant biological behaviors of UM M23 cells, inhibit tumor growth and promote cell apoptosis.Its mechanism may be related to blocking the activation of Wnt/β-catenin pathway.

Clinical study on the expression of EGFR in pancreatic adenosquamous carcinoma / 中华肝胆外科杂志

Objective:Exploration of epidermal growth factor receptor (EGFR) expression and its clinical significance in pancreatic adenosquamous carcinoma (PASC).Methods:A total of 60 pancreatic cancer tissue samples and 8 normal pancreatic tissue samples were obtained from patients who were surgically treated at Beijing Chao-Yang Hospital, Capital Medical University from January 2016 to December 2021. A retrospective analysis of the clinical and pathological data of these 60 patients was conducted, including 23 males and 37 females with an age of (62.7±10.2) years. Among them, 20 cases were pathologically diagnosed as PASC, and 40 contemporaneous cases of pancreatic ductal adenocarcinoma (PDAC) were selected through propensity score matching. Immunohistochemistry (IHC) staining was used to measure the integrated optical density (IOD) of EGFR expression, and quantitative polymerase chain reaction (qPCR) was employed to detect the expression differences of EGFR mRNA. Based on the median IOD value of EGFR, the 20 PASC samples were divided into two groups, high and low expression groups. Kaplan-Meier survival analysis was performed to compare the impact of EGFR expression on the prognosis of PASC patients.Results:The IOD value of EGFR in PASC group (29.2 [25.7, 35.1]) was significantly higher than that in the PDAC group [9.5 (5.5, 13.0)] and they both exceeded the value in normal tissues [2.4 (1.7, 3.1)], with statistical significances ( all P<0.001 ). The level of EGFR mRNA expression in the PASC group was higher than that in the PDAC group [3.0 (1.8, 3.5) vs 1.2 (0.8, 1.2)], showing statistically significant difference ( P=0.0079). Patients with high EGFR expression had shorter overall survival compared with patients with low expression ( P=0.002). The incidence of vascular invasion in the PASC group [40.0% (8/20)] was higher than that in the PDAC group [17.5% (7/40)], with a significant difference ( P=0.002). The median survival time for the PASC group was 16.00 (9.25, 25.25) months, which was shorter than that of the PDAC group 21.50 (11.25, 40.75) months, showing a statistically significant difference ( P=0.033). The overall survival rate of the PASC group was lower than PDAC group ( P=0.028). Conclusion:EGFR expression is significantly elevated in PASC tissues and PASC patients have poor prognosis.

Research and evaluation on dynamic accumulation of dry matter and quality of Isatis indigotica in Longdong area / 中成药

AIM To explore the laws in accumulation of dry matter and medicinal ingredients of Isatis indigotica Fort.in Longdong area,and determine the best harvest time to obtain the high-quality and high-yield medicinal plant.METHODS The I.indigotica had its agronomic traits investigated regularly;the accumulation laws of its uridine,guanosine,(R,S)-geichan and adenosine measured by HPLC;and its comprehensive utilization value in different periods evaluated by grey correlation method.RESULTS There existed significant variations among the plant height,plant width,leaf length,leaf width,number of leaves,leaf weight,root length,root diameter,root weight,and the yields of uridine,guanosine,(R,S)-goitrin and adenosine at different growth stages,whose peak values appeared in different period.Additionally,there were also obvious differences in the aforementioned indexes levels among different strains.The highest weighted correlation degree of the comprehensive utilization value of Longde and 2008-6-2 on October 9,and of 2008-11 and 2016-2 on October 24.On the whole,the 2008-6-2 and 2016-2 were superior to 2008-11 and Longde.CONCLUSION It is suggested that the best harvest time of I.indigotica in Longdong area is in mid to late October.

Optimal repair timing and predictors of death in patients with ventricular septal rupture post myocardial infarction / 中华胸心血管外科杂志

Objective:The main objective of this study was to analyze the optimal timing for repair of post-AMI ventricular septal rupture(VSR). Secondary endpoints were to determine which factors could influence in-hospital mortality in the patients with VSR.Methods:We designed an observational, retrospective study, selecting 100 patients with post-AMI VSR between January 1, 2019 and August 31, 2023, with inclusion and exclusion criteria. Analyzed the usefulness and appropriate timing of surgery in this patient cohort. Compared the background characteristics, treatment and laboratory data between survival and death group. The risk factors for in-hospital mortality were assessed using multivariate analysis with a logistic regression model. Results:The overall in-hospital mortality rate was 56%, the mortality rate of surgical patients was 34.9%, and the mortality rate of conservative patients was 91.9%. Patients operated on very early(0-3 days) had significantly poor results with a mortality rate of 63.6% while those operated within 2 weeks, had a mortality rate of 38.1%, and those operated later(>14 days) showed 22.6% mortality.There were statistically significant differences between the two groups in terms of heart rate, ratio of revascularization , size of VSR, shock stage and severity of coronary artery lesions( P<0.05), and the C-reactive protein, WBC count, BNP level, creatinine level and blood lactate level in the death group were higher than those in the survival group( P<0.05). Logistic regression analysis revealed that the level of white blood cell count, lactate and brain natriuretic peptide were independent risk factors for in-hospital mortality. Conclusion:In our study, we observed that surgery is the definitive therapy for the majority of patients.For patients who are hemodynamically stable and have compensated heart failure, there may be more benefit from delayed ventricular septal rupture repair. The risk factors for in-hospital mortality were the elevated lactate levels, BNP levels and WBC count.

Application of proprioceptive assessment in children with cerebral palsy / 中国儿童保健杂志

Sensory dysfunction is a common clinical problem for children with cerebral palsy.Proprioception plays a key role in maintaining postural adjustment and balance coordination, so proprioceptive assessment is of great significance for further rehabilitation of children with cerebral palsy.At present, proprioception assessment is mainly used in adults such as stroke and joint injury, but there is still a lack of research in children, especially in children with cerebral palsy.Therefore, this paper aims to review the evaluation of proprioception of children with cerebral palsy at home and abroad.

Research progress of mass-spectrometric technique in nucleic acid detection and analysis / 中华预防医学杂志

Mass spectrometry is a spectroscopic technique for detecting the molecular weight of substances based on mass spectrometry equipment. Many types of mass spectrometry with different functions are widely used in scientific research and application technology development in various disciplines. In recent years, mass spectrometry has shown great potential in nucleic acid detection. In particular, matrix-assisted laser desorption/ionization time of flight mass spectrometry has become a research hotspot due to its velocity, high throughput, and accuracy. The nucleic acid research by mass spectrometry is highlighted in single nucleotide polymorphism, gene mutation, DNA methylation analysis, and DNA copy number variations. This article reviews the research and application of mass spectrometry in nucleic acid detection and analysis to provide a reference for the development of new detection technology for nucleic acid based on mass spectrometry.

Research progress of mass-spectrometric technique in nucleic acid detection and analysis / 中华预防医学杂志

Mass spectrometry is a spectroscopic technique for detecting the molecular weight of substances based on mass spectrometry equipment. Many types of mass spectrometry with different functions are widely used in scientific research and application technology development in various disciplines. In recent years, mass spectrometry has shown great potential in nucleic acid detection. In particular, matrix-assisted laser desorption/ionization time of flight mass spectrometry has become a research hotspot due to its velocity, high throughput, and accuracy. The nucleic acid research by mass spectrometry is highlighted in single nucleotide polymorphism, gene mutation, DNA methylation analysis, and DNA copy number variations. This article reviews the research and application of mass spectrometry in nucleic acid detection and analysis to provide a reference for the development of new detection technology for nucleic acid based on mass spectrometry.

Role of podoplanin in hepatic stellate cell activation and liver fibrosis / 临床肝胆病杂志

ObjectiveTo investigate the role and mechanism of podoplanin （PDPN） in hepatic stellate cell （HSC） activation and liver fibrosis. MethodsLiver biopsy samples were collected from 75 patients with chronic hepatitis B who attended Department of Infectious Diseases， Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine， for the first time from September 2019 to June 2022， and RT-PCR and immunohistochemistry were used to measure the expression of PDPN in liver tissue of patients in different stages of liver fibrosis. A total of 12 male C57/BL6 mice were randomly divided into control group and model group. The mice in the model group were given intraperitoneal injection of 10% CCl4， and those in the control group were injected with an equal volume of olive oil， for 6 weeks. HE staining and Sirius Red staining were used to observe liver histopathological changes； primary mouse liver cells were separated to measure the mRNA expression of PDPN in various types of cells； primary mouse HSCs were treated with PDPN protein， followed by treatment with the NF-‍κB inhibitor BAY11-708， to measure the expression of inflammatory factors in HSCs induced by PDPN. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Spearman correlation analysis was used to investigate data correlation. ResultsAs for the liver biopsy samples， there was a relatively low mRNA expression level of PDPN in normal liver， and there was a significant increase in the mRNA expression level of PDPN in liver tissue of stage S3 or S4 fibrosis （all P<0.001）. Immunohistochemical staining showed that PDPN was mainly expressed in the fibrous septum and the hepatic sinusoid， and the PDPN-positive area in S4 liver tissue was significantly higher than that in S0 liver tissue （t=8.892， P=0.001）. In normal mice， PDPN was mainly expressed in the hepatic sinusoid， and there was a significant increase in the expression of PDPN in CCl4 model mice （t=0.95， P<0.001）， mainly in the fibrous septum. RT-PCR showed a significant increase in the mRNA expression of PDPN in the CCl4 model mice （t=11.25， P=0.002）. Compared with hepatocytes， HSCs， Kupffer cells， and bile duct endothelial cells， hepatic sinusoidal endothelial cells showed a significantly high expression level of PDPN （F=20.56， P<0.001）. Compared with the control group， the primary mouse HSCs treated by PDPN protein for 15 minutes showed significant increases in the mRNA expression levels of the inflammation-related factors TNFα， CCL3， CXCL1， and CXCR1 （all P<0.05）， and there were significant reductions in the levels of these indicators after treatment with BAY11-7082 （all P<0.05）. ConclusionThere is an increase in the expression of PDPN mainly in hepatic sinusoidal endothelial cells during liver fibrosis， and PDPN regulates HSC activation and promotes the progression of liver fibrosis via the NF-κB signaling pathway.

Therapeutic effect of Xiayuxue decoction on a mouse model of nonalcoholic fatty liver disease induced by high-fat diet and its mechanism / 临床肝胆病杂志

ObjectiveTo investigate the mechanism of action of Xiayuxue decoction in inhibiting nonalcoholic fatty liver disease （NAFLD） induced by high-fat diet in mice by regulating nucleotide binding oligomerization domain like receptor containing pyrin domain protein 6 （NLRP6）. MethodsA total of 15 male C57BL/6 mice were randomly divided into low-fat diet （LFD） group， high-fat diet （HFD） group， and Xiayuxue decoction-HFD group （XYXD group）， with 5 mice in each group. Liver function parameters （alanine aminotransferase ［ALT］ and aspartate aminotransferase ［AST］） and blood lipid metabolic indicators （triglycerides ［TG］ and total cholesterol ［TC］） were measured； HE staining and oil red O staining were performed for liver tissue to observe histomorpholoty and lipid droplet deposition； quantitative real-time PCR was used to measure the expression levels of inflammatory factors （tumor necrosis factor-α ［TNF-α］， interleukin-1β ［IL-1β］， interleukin-18 ［IL-18］， and NLRP6） in liver tissue； Western blot was used to measure the protein expression levels of NLRP6， nuclear factor-kappa B （NF-κB）， and NF-κB p65； immunohistochemistry was used to measure the expression of NLRP6 and CD68. Mouse Raw264.7 cells were treated with palmitic acid （PA）， lipopolysaccharide， and serum containing Xiayuxue decoction to observe inflammation. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the LFD group， the HFD group had significant increases in the serum levels of ALT， AST， TC， and TG （all P<0.05）. Liver histopathological examination showed that the HFD group had marked hepatic steatosis and a signficant increase in NAS score （P<0.05）， and quantitative real-time PCR showed significant increases in the inflammatory factors such as IL1β and IL-18 and a significant reduction in the expression of NLRP6 （all P<0.05）. Immunohistochemistry showed that the expression of NLRP6 showed a similar trend as that of the macrophage marker CD68. Western blot showed that after the downregulation of NLRP6 expression， there was a significant increase in phosphorylated NF-κB p65 （P<0.05）. Compared with the HFD group， Xiayuxue decoction effectively improved liver inflammation， upregulated the expression of NLRP6， and downregulated phosphorylated NF-κB p65 in HFD mice （all P<0.05）. After Raw264.7 cells were treated with PA， NLRP6 was downregulated to promote the progression of inflammation （P<0.05）， and treatment with Xiayuxue decoction could upregulate NLRP6 and inhibit inflammation NF-κB （P<0.05）. ConclusionXiayuxue decoction can effectively improve hepatic steatosis and liver inflammation in a mouse model of NAFLD， possibly by regulating NLRP6/NF-κB to alleviate macrophage activation.

Human hair follicle-derived mesenchymal stem cells promote tendon repair in a rabbit Achilles tendinopathy model / 中华医学杂志(英文版)

BACKGROUND@#Hair follicles are easily accessible and contain stem cells with different developmental origins, including mesenchymal stem cells (MSCs), that consequently reveal the potential of human hair follicle (hHF)-derived MSCs in repair and regeneration. However, the role of hHF-MSCs in Achilles tendinopathy (AT) remains unclear. The present study investigated the effects of hHF-MSCs on Achilles tendon repair in rabbits.@*METHODS@#First, we extracted and characterized hHF-MSCs. Then, a rabbit tendinopathy model was constructed to analyze the ability of hHF-MSCs to promote repair in vivo . Anatomical observation and pathological and biomechanical analyses were performed to determine the effect of hHF-MSCs on AT, and quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical staining were performed to explore the molecular mechanisms through which hHF-MSCs affects AT. Furthermore, statistical analyses were performed using independent sample t test, one-way analysis of variance (ANOVA), and one-way repeated measures multivariate ANOVA as appropriate.@*RESULTS@#Flow cytometry, a trilineage-induced differentiation test, confirmed that hHF-derived stem cells were derived from MSCs. The effect of hHF-MSCs on AT revealed that the Achilles tendon was anatomically healthy, as well as the maximum load carried by the Achilles tendon and hydroxyproline proteomic levels were increased. Moreover, collagen I and III were upregulated in rabbit AT treated with hHF-MSCs (compared with AT group; P  < 0.05). Analysis of the molecular mechanisms revealed that hHF-MSCs promoted collagen fiber regeneration, possibly through Tenascin-C (TNC) upregulation and matrix metalloproteinase (MMP)-9 downregulation.@*CONCLUSIONS@#hHF-MSCs can be a treatment modality to promote AT repair in rabbits by upregulating collagen I and III. Further analysis revealed that treatment of AT using hHF-MSCs promoted the regeneration of collagen fiber, possibly because of upregulation of TNC and downregulation of MMP-9, thus suggesting that hHF-MSCs are more promising for AT.

Effect of Wumeisan on Gut Lactase Activity and Microflora Diversity of Mice with Dysbacteriosis Diarrhea / 中国实验方剂学杂志

ObjectiveTo explore the effects of Wumeisan on gut lactase activity and microflora diversity of mice with dysbacteriosis diarrhea. MethodThe mice were randomly divided into 4 groups， namely， the normal group， the model group， and the low-dose and high-dose Wumeisan groups， with 8 mice in each group. The mouse model was made by gavage of mixed antibiotics for 7 d， and the low-dose and high-dose Wumeisan groups （5.98， 11.96 g·kg-1） were given gavage for 7 d continuously. The normal group and the model group were given the same volume of sterile water. The changes in the body weight， food intake， and diarrhea of mice were recorded. Feces were collected after the last administration， and the lactase activity was detected by the colorimetric method. The gut microbiota changes were detected by the 16S rRNA high-throughput sequencing technology. ResultCompared with those in the normal group， the mice in the model group had dilute and soft stools， reduced body mass， reduced food intake， reduced lactase activity， significantly reduced intestinal flora diversity， and significant changes in the relative abundance phylum and genus levels of flora. Compared with the model group， Wumeisan reduced the diarrhea rate of mice， promoted the rapid recovery of body weight and food intake， increased the lactase activity decreased by antibiotic， improved the community abundance and diversity of mice with dysbacteriosis， and made the species composition closer to that in the normal group. The abundance of three phyla （Bacteroidota， Proteobacteria， Verrucomicrobiota） and nine genera （Odoribacter， Enterococcus， Clostridium innocuum group， etc.） of mice with diarrhea were regulated by Wumeisan. Among them， norank f Muribaculaceae， norank f norank o Clostridia UCG-014， Lachnospiraceae NK4A136 group， and Odoribacter showed significant positive correlation with the body weight and lactase activity， and Escherichia-Shigella， Enterobacter， Enterococcus， and Clostridium innocuum group showed significant positive correlation with the diarrhea rate. Function prediction showed that the high-dose Wumeisan significantly reseted 6 functional levels of metabolism， genetic information processing， and human diseases， and had positive effects on endocrine and metabolic diseases， immune diseases， infectious disease， and parasitic infectious diseases. ConclusionWumeisan can relieve the symptoms of dysbacteriological diarrhea by increasing the lactase activity and regulating the gut microbiota composition.

Effect of acupuncture exercise therapy synchronizing isokinetic muscle strength training for postoperative rehabilitation of meniscectomy under arthroscopy / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture exercise therapy synchronizing isokinetic muscle strength training on the motor function, stability and proprioception of knee joint, as well as the anxiety emotion in patients after meniscectomy under arthroscopy.@*METHODS@#A total of 70 patients after meniscectomy under arthroscopy were randomized into an observation group (35 cases, 2 cases were eliminated， 2 cases dropped off) and a control group (35 cases, 2 cases were eliminated, 1 case dropped off). Acupuncture was applied at Chize (LU 5), Neixiyan (EX-LE 4), Dubi (ST 35),Yanglingquan (GB 34), etc. on the affective side in the two groups. After 30 min, the needles of the knee joint area were withdrew, while the needle at elbow was continuously retained, the observation group was given acupuncture exercise therapy synchronizing isokinetic muscle strength training, and the control group was given conventional acupuncture exercise therapy. The treatment was given once a day, 7-day treatment was taken as one course, and totally 4 courses were required in the two groups. Before and after treatment, the knee joint Lysholm score, the knee joint isokinetic muscle strength flexion/extension ratio (H/Q), joint position sense measurement (JPS) and Hamilton anxiety scale (HAMA) score were compared in the two groups.@*RESULTS@#After treatment, the knee joint Lysholm scores and H/Q were increased compared with those before treatment in the two groups (P<0.001), and the knee joint Lysholm score and H/Q in the observation group were higher than those in the control group (P<0.001); the JPS and HAMA scores were decreased compared with those before treatment in the two groups (P<0.001), the JPS and HAMA score in the observation group were lower than those in the control group (P<0.05).@*CONCLUSION@#Acupuncture exercise therapy synchronizing isokinetic muscle strength training can effectively improve the motor function, stability and proprioception of knee joint, as well as the anxiety emotion in patients after meniscectomy under arthroscopy.