Polyphyllin I enhances tumor necrosis factor-related apoptosis-inducing ligand-induced inhibition of human osteosarcoma cell growth downregulating the Wnt/ß-catenin pathway.

OBJECTIVE: To investigate the synergistic effects of polyphyllin I (PPI) combined with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on the growth of osteosarcoma cells through downregulating the Wnt/ß-catenin signaling pathway. METHODS: Cell viability, apoptosis and cell cycle distribution were examined using cell counting kit-8 and flow cytometry assays. The morphology of cancer cells was observed with inverted phase contrast microscope. The migration and invasion abilities were examined by xCELLigence real time cell analysis DP system and transwell assays. The expressions of poly (adenosine diphosphate-ribose) polymerase, C-Myc, Cyclin B1, cyclin-dependent kinases 1, N-cadherin, Vimentin, Active-ß-catenin, ß-catenin, p-glycogen synthase kinase 3ß (GSK-3ß) and GSK-3ß were determined by Western blotting assay. RESULTS: PPI sensitized TRAIL-induced decrease of viability, migration and invasion, as well as increase of apoptosis and cell cycle arrest of MG-63 and U-2 OS osteosarcoma cells. The synergistic effect of PPI with TRAIL in inhibiting the growth of osteosarcoma cells was at least partially realized through the inactivation of Wnt/ß-catenin signaling pathway. CONCLUSION: The combination of PPI and TRAIL is potentially a novel treatment strategy of osteosarcoma.

(5R)-5-hydroxytriptolide ameliorates diabetic kidney damage by inhibiting macrophage infiltration and its cross-talk with renal resident cells.

OBJECTIVE: Diabetic nephropathy (DN) is the main cause of end-stage renal disease, and there are no targeted treatment options at present. The efficacy of the new immunosuppressive drug (5R)-5-hydroxytriptolide (LLDT8) in improving kidney inflammation has been demonstrated in multiple studies. The present study was intended to investigate the preventive and therapeutic effects of LLDT8 on DN and to reveal its potential pharmacological mechanisms. METHODS: The effects of LLDT8 on liver and kidney functions, and urine microprotein of Streptozotocin (STZ) induced DN mice were detected. The protective effect of LLDT8 on the kidney tissue was observed by pathological staining and transmission electron microscopy. Cell culture experiments were performed to detect the effects of LLDT8 on the expression of chemokines and epithelial-mesenchymal transition (EMT) in high glucose-induced TCMK1 cells using real-time polymerase chain reaction (RT-PCR) and western blot (WB) techniques and to detect the influence of LLDT8 on the secretion of pro-inflammatory and pro-fibrotic factors in high glucose-induced RAW264.7 cells. RESULTS: In animal experiments, treatment with high-dose LLDT8 (0.25 mg/kg/2d) reduced 24 h urinary albumin excretion, improved structural kidney damage, and delayed fibrosis progression in DN mice. Immunofluorescence results showed that LLDT8 intervention reduced macrophage infiltration in kidney tissues of DN mice. PCR and WB results of kidney tissues showed reduced expressions of chemokines CCL2 and M-CSF1 in the LLDT8 intervention group compared to the DN group. In cellular assays, LLDT8 treatment reduced chemokine secretion in high glucose-induced TCMK1 cells, but had no effect on EMT of TCMK1 cells. LLDT8 treatment reduced the secretion of pro-inflammatory and pro-fibrotic factors in high glucose-induced RAW264.7 cells. CONCLUSIONS: The present study suggests that LLDT8 could effectively inhibit the secretion of pro-inflammatory and pro-fibrotic factors by macrophages, which could alleviate high glucose-induced renal tissue injury and slow down the process of tissue fibrosis and DN.

Expression pattern and signification of Cx43,beta-catenin and Smo in the second heart field / 中国组织工程研究

BACKGROUND:The second heart field is crucial for the development of the embryonic heart.Abnormal development of the second heart field can result in multiple cardiac malformations.After Cx43 gene knockout,reduced formation and proliferation of cells of the second heart field can be observed,but the specific reason remains unclear. OBJECTIVE:(1)To determine whether β-catenin,Smo and Cx43 were co-expressed in the second heart field and the endoderm,we observed the expression patterns of these proteins.(2)To explore whether Cx43 interacts with the Wnt/β-catenin pathway or the Shh pathway in the development of the second heart field. METHODS:Serial paraffin sections of the mouse embryos at embryonic days 10-12 were selected for immunohistochemical staining,hematoxylin-eosin staining and immunofluorescence staining.The primitive gut of mouse embryos at embryonic day 11 was separated for western blot assay and co-immunoprecipitation. RESULTS AND CONCLUSION:(1)Cx43 and Isl1 were co-expressed in some mesenchymal cells on the ventral side of the foregut and dorsal wall of the pericardial cavity of mouse embryos at embryonic days 10-12;Isl1 positive cells increased while Cx43 positive cells increased.(2)Cx43 and β-catenin were co-expressed in the ventral part of the endoderm at embryonic days 10-12.(3)Cx43 and Smo were co-expressed in the endoderm at embryonic days 10-12.(4)The co-immunoprecipitation results confirmed that there was an interaction between Cx43 and β-catenin,which suggested that Cx43 interacted with β-catenin to participate in the development of the second heart field.

Correlations between brain function and olfactory function in patients with cerebral small vessel disease and Parkinson's disease based on resting-state functional magnetic resonance imaging / 中国组织工程研究

BACKGROUND:Olfactory dysfunction is an early biological marker of various diseases.However,the neuroimaging mechanism by which olfactory dysfunction occurs following cerebral small vessel disease is unclear. OBJECTIVE:To explore the different neuroimaging mechanisms of olfactory function regulation in patients with cerebral small vessel disease and Parkinson's disease,and explore the potential application value of olfactory function assessment in patients with cerebral small vessel disease. METHODS:Neuropsychological and olfactory tests,high-resolution structural magnetic resonance and resting-state functional magnetic resonance data were collected in 80 patients with cerebral small vessel disease,44 healthy controls and 29 patients with Parkinson's disease.DPABI,SPM12 and SPSS were used to analyze and compare the amplitude of low frequency fluctuation,regional homogeneity and functional connectivity values between the cerebral small vessel disease,control and Parkinson's disease groups.Correlations between the significantly altered resting-state functional magnetic resonance imaging measures and olfactory and cognitive scores were evaluated. RESULTS AND CONCLUSION:Compared with the control group,low-frequency fluctuation amplitude of the right dorsolateral superior frontal gyrus and the regional homogeneity of the left wedge leaf were significantly reduced in the cerebral small vessel disease and Parkinson's disease groups.The right dorsolateral superior frontal gyrus and the left cuneiform lobe are the seed points.Compared with the Parkinson's disease group,the functional connectivity values of the right anterior cunei,inferior temporal gyrus,anterior central gyrus and dorsolateral superior frontal gyrus,left posterior central gyrus and inferior temporal gyrus were significantly enhanced in the control and cerebral small vessel disease groups.The left cuneiform lobe was the seed point.Compared with the control group,the functional connectivity of the left lingual gyrus was significantly weakened in the cerebral small vessel disease and Parkinson's disease groups.The functional connectivity values of the left middle temporal gyrus and the right posterior central gyrus were enhanced in the control group compared with the cerebral small vessel disease and Parkinson's disease group,and that was enhanced in the cerebral small vessel disease group compared with the Parkinson's disease group.Correlation analysis showed that the olfactory score and cognitive score were positively correlated in the cerebral small vessel disease group,and the regional homogeneity of the left wedge lobe was negatively correlated with the Montreal Cognitive Assessment Scale score,while the functional connectivity of left wedge lobe-left middle temporal gyrus in the Parkinson's disease group was positively correlated with the olfactory recognition score,and the functional connectivity values of the left wedge lobe-left posterior central gyrus and left wedge lobe-left lingual gyrus were positively correlated with the olfactory identification score and the total olfactory score,respectively.The regulation of olfactory function in patients with cerebral small vessel disease has a different neuroimaging mechanism from that of olfactory dysfunction in patients with Parkinson's disease.The olfactory function of patients with cerebral small vessel disease is related to cognitive function.It is speculated that the olfactory function following cerebral small vessel disease is a secondary change of brain dysfunction,while olfactory dysfunction following Parkinson's disease is directly caused by abnormal function of olfactory-related brain areas.Olfactory function assessment in patients with cerebral small vessel disease has potential application in predicting cognitive function.

Study on the mechanism of herb cake-partitioned moxibustion inhibiting tumor growth in colitis-associated colorectal cancer based on KDM4D receptor / 针灸推拿医学（英文版）

Objective:To explore the inhibitory mechanism of herb cake-partitioned moxibustion on tumor growth in colitis-associated colorectal cancer(CAC)based on histone lysine demethylase 4D(KDM4D). Methods:Inbred male Sprague-Dawley rats were randomly divided into a normal group,a CAC group,a herb cake-partitioned moxibustion group,and an inhibitor group.Except the normal group,rats in the other three groups were treated with azoxymethane(AOM)combined with dextran sulfate sodium(DSS)to make CAC rat models.Rats in the normal group and the CAC group did not receive interventions;rats in the herb cake-partitioned moxibustion group received moxibustion at Qihai(CV6)and bilateral Tianshu(ST25),2 cones for one point each time,once a day for 30 d with 1-day rest every week;rats in the inhibitor group received intraperitoneal injection of KDM4D inhibitor,5-chloro-8-hydroxyquinoline(5-c-8HQ),once a day for 30 d.After intervention,the general condition,colon length,tumor number and volume,and histopathological colon changes were observed.The expression of adenomatous polyposis coli(APC),axis inhibitor(Axin),cyclin D1,matrix metalloproteinase(MMP)-7 and MMP-9 mRNAs were detected by real-time quantitative polymerase chain reaction.The proliferating cell nuclear antigen(PCNA),cleaved caspase3,KDM4D,APC,and Axin proteins were detected by immunohistochemistry. Results:Compared with the normal group,the general condition was poor,the colon length was significantly shortened(P<0.01),the number and volume of colonic tumors were increased(P<0.01),the structure of glandular duct was obviously disordered with"back-to-back"and cowall phenomenon,and also high-grade adenocarcinoma formed;the protein expression levels of PCNA and KDM4D were significantly increased(P<0.01),while cleaved caspase3,APC,and Axin were significantly reduced(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were significantly increased(P<0.01),while APC and Axin were significantly reduced(P<0.01)in the CAC group.Compared with the CAC group,the general condition was improved,the length of colon was significantly increased(P<0.01),the number and volume of the colonic tumors were reduced(P<0.05),and the colon tissues showed epithelial cell proliferation with enlarged and deep staining nuclei,dysplasia and inflammatory cell infiltration;the protein expression levels of PCNA and KDM4D were significantly reduced(P<0.01),while the cleaved caspase3,APC,and Axin were significantly increased(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were reduced(P<0.05),while the APC and Axin were increased(P<0.05)in the colon tissues of rats in the herb cake-partitioned moxibustion group and the inhibitor group. Conclusion:Herb cake-partitioned moxibustion regulated abnormally expressed KDM4D in CAC rats,activated APC and Axin,the upstream molecules of Wnt/β-catenin pathway,inhibited abnormally activated downstream molecules of Wnt/β-catenin pathway.This may be a key mechanism of herb cake-partitioned moxibustion in inhibiting CAC tumor growth.

Effects of Tuina static training on vascular endothelial cell dysfunction and adiponectin in obese rats / 针灸推拿医学（英文版）

Objective:To observe the effects and explore the mechanism of Tuina(Chinese therapeutic massage)static training on vascular endothelial cell dysfunction and adiponectin(APN)in obese rats. Methods:Eight of 40 Sprague-Dawley rats were randomly selected as a normal group to be fed a common diet.The remaining rats were fed a high-fat diet to induce obesity models and randomly divided into a model group,an aerobic exercise group,and a static training group after successful modeling,with 8 rats in each group.During the entire experiment,rats in the normal group were fed a common diet without intervention.Rats in the model group were fed a high-fat diet without intervention.Rats in the aerobic exercise group were given moderate-intensity running exercises.Rats in the static training group were given 6-day/week static training for 8 weeks.The body mass and length of rats were recorded throughout the experiment,and the Lee's index was calculated.After the intervention,the perirenal and peri-epididymal fat weights of rats were measured,and the fat/body mass ratio was calculated.Four items of blood lipids were detected by biochemical methods[triglyceride(TG),total cholesterol(TC),low-density lipoprotein(LDL),and high-density lipoprotein(HDL)];serum nitric oxide(NO),endothelin-1(ET-1),soluble thrombomodulin(sTM),and APN were detected by enzyme-linked immunosorbent assay.The morphological changes of the aorta in each group were observed under the microscope. Results:Compared with the normal group,the body mass,body length,Lee's index,perirenal fat mass,peri-epididymal fat mass,fat/body mass ratio,TG,TC,LDL,ET-1,and sTM in the model group were significantly increased(P<0.05),while the HDL,NO,and APN were significantly reduced(P<0.01).Compared with the model group,the body mass,Lee's index,perirenal fat mass,peri-epididymal mass,fat/body mass ratio,TC,LDL,ET-1,and sTM in the aerobic exercise group and the static training group were significantly reduced(P<0.05 or P<0.01),while the HDL,NO,and APN were significantly increased(P<0.05 or P<0.01).Compared with the aerobic exercise group,NO in the static training group was significantly higher(P<0.05).APN was positively correlated with NO(P<0.01),while APN was negatively correlated with ET-1 or sTM(P<0.01).Aortic morphological observation showed that the degree of endothelial injury in the aerobic exercise group and the static training group was less significant than that in the model group,and the improvement of endothelial cell morphology in the static training group was more notable than that in the aerobic exercise group. Conclusion:Tuina static training and aerobic exercise improved the aortic endothelial injury in obese rats,and the effect of Tuina static training was more significant.The mechanism of action may be related to regulating lipid metabolism and promoting APN secretion.

Effects of vibrating the abdomen on peripheral blood gastrointestinal hormones and gastrointestinal motility of young anorexia model rats / 针灸推拿医学（英文版）

Objective:To observe the therapeutic effect of vibrating the abdomen on anorexia model rats,as well as its effects on cholecystokinin octapeptide(CCK-8)and motilin(MTL)in the peripheral blood. Methods:Forty young rats were randomly divided into a normal group(n=10)and a modeling group(n=30).Rats in the normal group were fed common feed.The anorexia model was established by the etiological simulation method in the modeling group,and these rats were further randomly divided into a drug group,a vibrating abdomen group,and a model group 3 weeks after the anorexia model was induced,with 10 rats in each group.The drug group was given Jian Wei Xiao Shi Pian by intragastric administration at a dose of 0.72 g/(kg·bw)(0.72 g drug was dissolved in 10 mL purified water).The normal group and the model group were given purified water once a day in the morning.The vibrating abdomen group was treated with vibrating the abdomen once a day for 21 times.The body mass,food intake,serum CCK-8,MTL,gastrin(GAS),neurotensin(NT)levels,and the intestinal propulsion rate of rats in each group were measured. Results:Compared with the model group,the body mass,food intake,serum MTL and GAS levels,and the small intestine propulsion rate increased significantly,and the serum CCK-8 and NT levels,the gastric residual rate decreased significantly in the vibrating abdomen group and the drug group(P<0.05).There were no significant differences between the vibrating abdomen group and the drug group(P>0.05). Conclusion:Vibrating the abdomen increases the food intake and body mass of anorexia model rats,reduces the residue of gastric contents,improves the small intestine propulsion rate,and therefore has a good therapeutic effect on anorexia.The mechanism may be related to inhibiting the secretion of CCK-8 and NT in plasma and promoting the release of MTL and GAS in serum.

Effects of acupuncture and moxibustion at Feishu(BL13)on inflammatory responses and intestinal short-chain fatty acids in asthma model rats / 针灸推拿医学（英文版）

Objective:To observe the effects of acupuncture and moxibustion at Feishu(BL13)on inflammatory responses and intestinal short-chain fatty acids(SCFAs)in rats with asthma. Methods:Fifty-six Sprague-Dawley rats were randomly divided into a normal group(16 rats)and a modeling group(40 rats).Rats in the modeling group were subjected to establishing asthma models using ovalbumin(OVA).Model evaluation was conducted using 4 rats from each group.The remaining rats that successfully developed asthma were then randomly divided into a model group,an acupuncture group,and a moxibustion group,with 12 rats in each group.Rats in the acupuncture group received acupuncture treatments,and those in the moxibustion group received moxibustion treatments,both at Feishu(BL13)for 30 min.Following the treatments,the rats were exposed to atomization excitation with a 1%OVA solution for 20 min daily for 14 consecutive days.At the end of the experiment,inflammatory markers in the rats'peripheral blood were analyzed using a biochemical method.In addition,inflammatory cells in the bronchoalveolar lavage fluid(BALF)were counted using Wright-Giemsa staining.The lung tissue of rats was examined under a light microscope after staining with hematoxylin-eosin to observe morphological or pathological changes.Furthermore,real-time fluorescence quantitative polymerase chain reaction was utilized to measure the mRNA expression of inflammatory factors in the lung tissue.Lastly,the concentration of SCFAs in the rat's feces was determined using gas chromatography-hydrogen flame ionization. Results:The levels of eosinophils(Eos),neutrophils(Neu),and lymphocytes(Lym)in the peripheral blood,as well as Eos and Neu in the BALF,and the expression of interleukin(IL)-4,IL-5,IL-13,IL-33,and thymic stromal lymphopoietin(TSLP)mRNAs in the lung tissue were all found to be significantly increased(P<0.05 or P<0.01);the lung tissue structure displayed severe injuries;the levels of acetic acid,propionic acid,isobutyric acid,butyric acid,and valeric acid in the feces decreased significantly in the model group(P<0.05 or P<0.01).Compared with the model group,the peripheral blood levels of Eos,Neu,and Lym,as well as Eos in the BALF,and the mRNA expression levels of IL-4 and IL-5 in the lung tissue decreased significantly in both the acupuncture group and the moxibustion group(P<0.05 or P<0.01).This reduction was accompanied by alleviated pathological damage in the lung tissue.Additionally,there were significant increases in the levels of acetic acid,propionic acid,isobutyric acid,and butyric acid in the feces in both the acupuncture group and the moxibustion group(P<0.05 or P<0.01).In the acupuncture group,the expression levels of Lym in the BALF and IL-13 mRNA in the lung tissue decreased significantly(P<0.05 or P<0.01).In the moxibustion group,the mRNA expression levels of IL-33 and TSLP in the lung tissue also reduced significantly(P<0.05 or P<0.01).Furthermore,the level of valeric acid in the feces increased notably in the moxibustion group(P<0.01).Compared with the acupuncture group,it was found that the mRNA levels of IL-5 and IL-13 in the lung tissue,as well as the acetic acid level in the feces,were significantly higher in the moxibustion group(P<0.05 or P<0.01). Conclusion:Both acupuncture and moxibustion were effective in reducing abnormal inflammation and regulating intestinal SCFAs in asthma model rats.Acupuncture demonstrated superiority in inhibiting pro-inflammatory factors,particularly IL-5 and IL-13,while moxibustion exhibited better regulation on intestinal metabolites SCFAs,especially acetic acid.

Infrared spectrum analysis of Taichong(LR3)and Taixi(KI3)points before and after menstruation in healthy women / 针灸推拿医学（英文版）

Objective:To investigate the variations in infrared radiation at Taichong(LR3),Taixi(KI3),and control points before and after menstruation and to examine the infrared radiation patterns associated with Yuan-primordial points of Zang-Fu organs during the physiological menstrual cycle. Methods:Using a point infrared radiation spectrum detection system,we detected the infrared radiation spectra of Taichong(LR3),Taixi(KI3),and the control points located 1 cm away from the two points,in a range of 1.50-18.00 μm wavelengths during the premenstrual,menstrual,and postmenstrual phases in 32 healthy adult women.Subsequently,data mining and analysis were conducted. Results:Before,during,and after menstruation,the infrared spectral shapes of bilateral Taichong(LR3),Taixi(KI3),and their control points were generally consistent,with characteristic infrared spectral wavelengths located at 11.25 μm.Prior to menstruation,the total intensity of infrared radiation at the right Taixi(KI3)was significantly lower than that at the control point(P<0.05),and that at the left Taichong(LR3)was significantly lower than that at the control point(P<0.01).During and after menstruation,the total infrared radiation intensity at both Taixi(KI3)was significantly lower than that of the control point(P<0.05).The wavelength points exhibiting significant differences in the infrared radiation intensity between points and control points were concentrated at the primary peak of 7.50-14.25 μm and the secondary peak of 15.00-17.25 μm. Conclusion:During different menstrual phases,the infrared radiation spectra of Taichong(LR3)and Taixi(KI3)exhibited distinct point specificity,mainly evident in the infrared radiation intensity and wavelength.

Relationship between sensory characteristics and gray matter volumes in children with autism spectrum disorders / 中国学校卫生

Objective@#To investigate the potential relationship between sensory characteristics and gray matter volumes in children with autism spectrum disorders (ASD), to provide a basis for the diagnosis and treatment of children with ASD.@*Methods@#A total of 40 ASD children who were treated or recovered in Xi an medical institutions and 16 typically developing (TD) children who were from several kindergatens in Xi an were invited for participation. Sensory characteristics were evaluated by the sensory processing and self regulation checklist, 3D structural brain images were obtained with TIWI, and gray matter volumes were analyzed by voxel based morphometry. Sensory characteristics and gray matter volumes were compared between groups and the relationship between sensory characteristics and different gray matter volumes were analyzed.@*Results@#The scores of auditory, visual, tactile, sensory processing ability and sensory under responsivity in the ASD group were lower than those in the TD group ( Z/t =-2.63, -2.57 , -3.11, -2.19, -3.83, P <0.05). Gray matter volumes in nine brain regions increased in the ASD group compared to the TD group, including the left and right posterior inferior lobe, right parahippocamal gyrus, left insula, left media frontal gyrus, left superion occipital gyrus, right superion occipital gyrus, right superion parietal lobe, and right posterion central gyrus ( t =3.53, 3.69 , 3.37, 3.86, 3.61, 3.37, 4.04, 3.38, 3.16, P <0.01). In the ASD group, the scores of visual, vestibular, proprioceptive, sensory processing ability, sensory seeking behavior and sensory over responsivity were negatively correlated with gray matter volumes of left superior occipital gyrus ( r =-0.36, -0.40, -0.39, -0.36, -0.40, -0.36), and the scores of visual, vestibular, and sensory over responsivity were negatively correlated with gray matter volumes of the right superior parietal lobule ( r =-0.36, -0.50, -0.42)( P <0.05).@*Conclusion@#The presence of paresthesia in children with ASD is associated with gray matter volumes of the left superior occipital gyrus and right superior parietal lobule.

Distribution of pathogenic bacteria of bloodstream infection after chemotherapy in patients with acute leukemia and risk factors analysis of the occurrence of adverse events and prediction model construction / 白血病·淋巴瘤

Objective:To investigate the distribution of pathogenic bacteria of bloodstream infection after chemotherapy in patients with acute leukemia (AL), to analyze the risk factors for the occurrence of adverse events and to construct a nomogram model to predict the occurrence of adverse events.Methods:The clinical data of 313 AL patients with bloodstream infection who were admitted to the First Hospital of Jilin University from January 2018 to December 2020 were retrospectively analyzed, and the incidence, fatality and distribution characteristics of pathogenic bacteria after chemotherapy in AL patients were analyzed; the occurrence of adverse events (death or infectious shock) in patients with different clinicopathological characteristics were compared. Unconditional logistic binary regression model multifactor analysis was used to screen independent risk factors for the occurrence of adverse events in AL patients with bloodstream infection after chemotherapy; the nomogram model for predicting the occurrence of adverse events was developed by using R software; the Hosmer-Lemeshow test was used to verify the predictive effect of the model.Results:Of the 313 AL patients, the overall fatality rate was 4.2% (13/313), the all-cause fatality rate of bloodstream infection was 3.5% (11/313). Of the 313 cases, 254 cases (81.1%) were Gram-negative bacteria infection, mainly including 115 cases (45.3%) of Escherichia coli, 80 cases (31.5%) of Klebsiella pneumoniae, and 29 cases (11.4%) of Pseudomonas aeruginosa, and 10 cases (3.9%) died; 51 cases (16.3%) were Gram-positive cocci infection, mainly including 22 cases (43.1%) of Streptococcus spp., 20 cases (39.2%) of Staphylococcus spp., 7 cases (13.7%) of Enterococcus faecalis, and 0 case died; 8 cases (2.6%) were fungal infection, including 4 cases (1.3%) of Candida tropicalis, 2 cases (0.6%) of Candida subsmoothis, 1 case (0.3%) of Candida smooth, 1 case (0.3%) of new Cryptococcus, and 3 cases (37.5%) died. The differences in the occurrence rates of adverse events were statistically significant when comparing different treatment stage, risk stratification, timing of sensitive antibiotic use, total duration of fever, and glucocorticoid use in chemotherapy regimen, infecting bacteria carbapenem resistance, and leukemia remission (all P < 0.05). The results of logistic binary regression analysis showed that the use of glucocorticoid in chemotherapy regimen, the total duration of fever ≥7 d, the timing of sensitive antibiotic use ≥24 h, and carbapenem resistance of the infecting bacteria were independent risk factors for the occurrence of adverse events in AL patients with bloodstream infection after chemotherapy (all P < 0.05). A nomogram prediction model for the occurrence of adverse events in AL patients with bloodstream infection was established, and the nomogram model was calibrated and validated with good calibration and discrimination. Conclusions:The pathogenic bacteria of bloodstream infection after chemotherapy in AL patients is mainly Gram-negative bacteria, and the presence of glucocorticoid in chemotherapy regimen, long total duration of fever, poor timing of sensitive antibiotics, and infecting bacteria carbapenem resistance are risk factors for the occurrence of adverse events in AL patients with bloodstream infection after chemotherapy, and the nomogram prediction model based on these factors has a reliable predictive ability for the occurrence of adverse events.

Study progression on mechanism of long non-coding RNAs regulating drug resistance in osteosarcoma / 国际肿瘤学杂志

Osteosarcoma is the most common primary solid bone malignancy. The main factor leading to recurrence and metastasis of osteosarcoma is resistance to chemotherapy drugs. Long non-coding RNAs can affect drug resistance in osteosarcoma by regulating epithelial-mesenchymal transition, cell autophagy, apoptosis, drug efflux, and cell cycle, suggesting that long non-coding RNAs may become new targets for drug resistance in osteosarcoma treatment.

Predictive value of thromboelastography combined with conventional coagulation tests for deep vein thrombosis in preoperative trauma patients / 中华急诊医学杂志

Objective:To analyze the relationship between preoperative deep vein thrombosis (DVT) and parameters of conventional coagulation tests (CCTs) and thromboelastography (TEG) in patients with acute trauma, and to establish a prediction model to screen out high-risk patients with preoperative DVT.Methods:The clinical data of patients with acute traumatic fracture admitted to the Emergency Intensive Care Unit of Shanghai Sixth People’s Hospital from January 2021 to June 2021 were retrospectively collected. According to whether preoperative DVT occurred, the patients were divided into the DVT group and non-DVT group. The differences of CCTs and TEG parameters at the same time were compared between the two groups. Logistic regression analysis was applied to identify independent risk factors for DVT after trauma. The receiver-operating characteristic curve analysis was employed to analyze the clinical value of those parameters to predict preoperative DVT.Results:Among 123 patients with acute traumatic fracture, 101 patients were treated with anticoagulation before operation, and 51 patients were diagnosed with DVT. There were significant differences in activated partial thromboplastin time, fibrinogen (Fib), D-Dimer, fibrinogen degradation products (FDPs), reaction time, clotting time, α angle, maximum amplitude (MA) and coagulation index between the DVT and non-DVT groups. D-Dimer and MA were independent risk factors for preoperative DVT in patients with traumatic fracture. Logistic regression equation was used to establish a prediction model: the predicting index = 0.101×D-Dimer +0.241×MA + (-18.190). The α angle (AUC=0.833, P<0.001), MA (AUC=0.904, P<0.001), coagulation index (AUC=0.914, P<0.001) of TEG versus Fib (AUC=0.684, P=0.001), D-Dimer (AUC=0.685, P<0.001) and FDPs (AUC=0.656, P=0.003) of CCTs had a higher diagnostic efficacy in developing DVT of lower extremity in patients with traumatic fracture, and of all the coagulation index was the best. However, the predictor of D-Dimer combined with MA had a better predictive value (AUC=0.926, P<0.001), and the best cut-off value was 0.32 with a sensitivity and specificity of 90.2% and 79.8%, respectively. Conclusions:Compared with CCTs, TEG has more advantages in predicting preoperative DVT in patients with traumatic fracture, and the predictor of D-Dimer combined with MA can screen out patients with high risk of DVT, which can be recommended for clinical application.

Electroacupuncture stimulation attenuates corpus striatum white matter injury in rats with cerebral ischemia by inhibition of Nogo-A/NgR pathway / 针灸推拿医学（英文版）

Objective:To investigate the effect and the mechanism of electroacupuncture(EA)on corpus striatum white matter injury in rats with focal cerebral ischemia(FCI).Methods:Forty-four specific-pathogen-free Sprague-Dawley rats were divided into a normal group(n=10),a sham-operation group(sham group,n=10),and a modeling group(n=24)using the random number table method.The normal group was a blank control.In the sham group,only the vessels and vagus nerve were isolated without embolization.The FCI rat model in the modeling group was replicated using the middle cerebral artery occlusion embolization method.The 20 successfully modeled rats were randomly divided into a model group and an EA group,with 10 rats in each group.Rats in the model group did not receive further treatment.Rats in the EA group received EA stimulation at Baihui(GV20)and the left Zusanli(ST36)24 h after the successful modeling,30 min each time,once a day for 14 d.On the 14th day of the experiment,rats in each group were scored for neurological deficits and then sacrificed,and brain tissues containing corpus striatum around the ischemic focus were paraffin-embedded from 5 rats in each group.Luxol fast blue(LFB)staining was used to detect damage changes in the white matter.The positive immunoreactive expression of myelin basic protein(MBP),myelin-associated growth inhibitor A(Nogo-A)and its receptor(NgR)in rat corpus striatum tissue was detected by immunohistochemistry staining,and then the protein expression of MBP,Nogo-A,and NgR in the corpus striatum tissue around the ischemic focus was determined by Western blotting.Results:Compared with the normal group and the sham group,the model group had a significantly higher neurological deficit score(P＜0.05)and fiber bundle injuries in the corpus striatum white matter,evidenced by a significantly lower mean optical density value of corpus striatum LFB staining(P＜0.05),a significantly lower MBP expression level(P＜0.05),and significantly higher Nogo-A and NgR protein expression levels(P＜0.05).Compared with the model group,the neurological deficit score was significantly lower(P＜0.05),the mean optical density value of LFB staining was significantly higher(P＜0.05),the MBP expression level was increased(P＜0.05),and the expression levels of Nogo-A and NgR proteins were decreased(P＜0.05)in the EA group.Conclusion:EA reduces the ischemia-induced corpus striatum white matter injury and improves neurological deficits.The mechanism may be related to the inhibition of Nogo-A/NgR activation.

Study on the antipyretic mechanism of large pushing Tianheshui for young rabbits with endotoxin-induced fever / 针灸推拿医学（英文版）

Objective:To observe the effect of large pushing Tianheshui manipulation intervention on the body temperature of young rabbits with endotoxin-induced fever and discuss its antipyretic mechanism.Methods:Thirty-two young rabbits meeting the standards were selected from 40 ordinary young male New Zealand rabbits after being adapted for 7 d,and randomly divided into a normal group,a model group,a large pushing Tianheshui group,and an ibuprofen group according to the random number table method,with 8 rabbits in each group.Rabbits in the model group,the large pushing Tianheshui group,and the ibuprofen group were subjected to preparing the endotoxin-induced fever model by intravenous lipopolysaccharide from the marginal ear vein.Rabbits in the large pushing Tianheshui group received Tuina(Chinese therapeutic massage)manipulation intervention 1.5 h and 2.5 h after modeling,respectively.Rabbits in the ibuprofen group were intragastrically given ibuprofen suspension 1.5 h after modeling.The dynamic changes in body temperature were observed for the young rabbits after fever modeling.Enzyme-linked immunosorbent assay was used to determine the content changes in positive mediators of hypothalamic body temperature,including prostaglandin(PG)E2 and cyclic adenosine monophosphate(cAMP),as well as negative mediators of hypothalamic body temperature,including arginine vasopressin(AVP)and α-melanocyte stimulating hormone(α-MSH).Results:The body temperature of the young rabbits in the model group was significantly higher than that in the normal group at 0.5-4.0 h,5.0 h,and 5.5 h after modeling(P＜0.01),showing two obvious fever peaks in the model group at 1.5 h and 3.0 h after modeling,respectively,with the highest peak at 1.5 h.Compared with the model group,body temperatures of the large pushing Tianheshui group and the ibuprofen group decreased significantly after 0.5 h of intervention(P＜0.05).Compared with the normal group,the contents of PGE2 and cAMP were significantly increased(P＜0.05),and the contents of AVP and α-MSH were significantly decreased(P＜0.01)in the hypothalamus of the model group.Compared with the model group,the contents of PGE2 and cAMP were significantly decreased(P＜0.01),and the levels of AVP and α-MSH were significantly increased(P＜0.01)in the hypothalamus in the large pushing Tianheshui group and the ibuprofen group.There were no significant differences in the PGE2,cAMP,AVP,and α-MSH contents in the hypothalamus between the ibuprofen group and the large pushing Tianheshui group(P＞0.05).Conclusion:Large pushing Tianheshui manipulation has a significant antipyretic effect on endotoxin-induced fever in young rabbits.The mechanism may be related to inhibiting the positive regulators(PGE2 and cAMP)and promoting the negative regulators(AVP and α-MSH)of hypothalamic control of body temperature.

Effects of different moxibustion time on knee cartilage morphology and the expression of TNF-α and IL-10 in rats with knee osteoarthritis / 针灸推拿医学（英文版）

Objective:To observe the effects of different moxibustion time on cartilage morphology,tumor necrosis factor(TNF)-α and interleukin(IL)-10 of the knee joint in rats with knee osteoarthritis(KOA),and to explore the best treatment time of moxibustion for KOA.Methods:Healthy male Wistar rats were randomly divided into a blank group,a model group,a 15-minute-moxibustion group,a 30-minute-moxibustion group,and a 60-minute-moxibustion group,with 10 rats in each group.Except for the blank group,the KOA model was established in all groups by injecting sodium iodoacetate solution into the knee joint cavity of rats.Rats in the 15-minute-moxibustion group,the 30-minute-moxibustion group,and the 60-minute-moxibustion group were all treated with mild moxibustion intervention for 15 min,30 min,and 60 min,respectively at Neixiyan(EX-LE4)and Dubi(ST35)points near the patella,3 times a week for 4 weeks,12 times in total.Rats in the blank group and the model group were fixed for 30 min without moxibustion intervention.Macroscopic observation for the smoothness of knee cartilage surface was performed after the intervention.Hematoxylin-eosin staining,toluidine blue staining,and Mankin score were used to evaluate the pathological changes in the cartilage.The expression levels of TNF-α and IL-10 in the serum were detected by enzyme-linked immunosorbent assay.Results:Compared with the blank group,the articular cartilage surface in the model group was rough,the chondrocyte arrangement was irregular,the Mankin score and the serum TNF-α expression were significantly increased(P＜0.05),while the expression of serum IL-10 was significantly decreased(P＜0.05).Compared with the model group,the articular cartilage surface was smoother,the chondrocytes were arranged neatly,the Mankin score and serum TNF-α expression level were significantly lower in the three moxibustion intervention groups(P＜0.05);the serum IL-10 level in the 30-minute-moxibustion group and the 60-minute-moxibustion group was increased significantly(P＜0.05).Compared with the 15-minute-moxibustion group,the articular cartilage surface in the 30-minute-moxibustion group and the 60-minute-moxibustion group was smoother,the chondrocyte arrangement was more regular,the Mankin score and the serum TNF-α level were decreased significantly(P＜0.05),and the serum IL-10 level was increased(P＜0.05).There was no significant difference in the serum TNF-α or IL-10 level between the 30-minute-moxibustion group and the 60-minute-moxibustion group(P＞0.05).Conclusion:Moxibustion can obviously improve the morphology and structure of KOA articular cartilage,protect articular cartilage,inhibit cartilage inflammation,and delay KOA cartilage degeneration.Moxibustion's effect is closely related to moxibustion time;the therapeutic effect of the 30-minute-moxibustion and the 60-minute-moxibustion is better than that of the 15-minute-moxibustion.

Regulating effects of Neiguan(PC6)and Gongsun(SP4)on hypothalamic-pituitary-adrenal axis in rats with functional dyspepsia / 针灸推拿医学（英文版）

Objective:To investigate the effects and the possible mechanisms of Neiguan(PC6)and Gongsun(SP4)on the hypothalamic-pituitary-adrenal(HPA)axis in rats with functional dyspepsia(FD),thus to provide a theoretical basis for the clinical application of the Eight Confluent Points.Methods:Forty specific-pathogen-free Sprague-Dawley rats were divided into a blank group,a model group,an electroacupuncture(EA)group,and a Western medicine group by the random number table method,with 10 rats in each group.Rats in the blank group did not receive modeling or intervention.Rats in the other three groups were subjected to the FD with mood disorder model using the compound etiology modeling method.After the successful modeling,rats in the model group did not receive any interventions,rats in the Western medicine group received deanxit and mosaprid intervention,and those in the EA group received EA intervention on the ipsilateral Neiguan(PC6)and Gongsun(SP4)for 21 d.The sugar-water consumption rate was measured before the experiment and before and after interventions to assess the emotional status.The gastric emptying rate was measured after interventions to assess the gastrointestinal dynamics.The expression levels of hypothalamic corticotropin-releasing hormone(CRH),pituitary adrenocorticotropic hormone(ACTH),and adrenal corticosterone(CORT)were measured by enzyme-linked immunosorbent assay.Results:Compared with the blank group,the sugar-water consumption rate and the gastric emptying rate were decreased(P<0.01),and the hypothalamic CRH,pituitary ACTH,and adrenal CORT expression levels were increased(P<0.01)in the model group.Compared with the model group,the sugar-water consumption rate and the gastric emptying rate were significantly increased(P<0.01),while the expression levels of hypothalamic CRH,pituitary ACTH,and adrenal CORT were significantly decreased(P<0.01)in the EA group and the Western medicine group.The differences between the EA group and the Western medicine group were not statistically significant(P>0.05).Conclusion:The Eight Confluent Points Neiguan(PC6)and Gongsun(SP4)can improve the mood and gastrointestinal dynamics in FD rats,which may be achieved by down-regulating the hypothalamic CRH,pituitary ACTH,and adrenal CORT,as well as by correcting the HPA axis hyperfunction.

Effects of acupuncture at Houxi(SI3)and Huantiao(GB30)on NF-κB/iNOS/NO pathway in lumbar disc herniation model rats / 针灸推拿医学（英文版）

Objective:To observe the effects of acupuncture at Houxi(SI3)and Huantiao(GB30)on the expression levels of nuclear factor kappa B(NF-κB),inducible nitric oxide synthase(iNOS),and nitric oxide(NO)of NF-κB inflammatory signaling pathway in L5 spinal nerve root of lumbar disc herniation(LDH)model rats and explore the mechanism of acupuncture in LDH treatment.Methods:Forty specific-pathogen-free healthy male Sprague-Dawley rats were randomly divided into a sham operation group,a model group,acupuncture group 1,and acupuncture group 2,with 10 rats in each group.The non-compression nucleus protrusion model was made by puncturing L4-L5 spinous process space and injecting autologous nucleus suspension.Acupuncture at bilateral Shenshu(BL23),Dachangshu(BL25),and Weizhong(BL40)was carried out in acupuncture group 1,and acupuncture at bilateral Houxi(SI3)and Huantiao(GB30)in acupuncture group 2.All rats were treated with balanced reinforcing and reducing needling manipulations,and the needles were retained for 30 min/time with one episode of needling manipulation every 10 min,once a day,14 times in total.The threshold value of paw withdrawal pain was measured by a thermal stimulation pain instrument;the serum NF-κB,iNOS,and NO levels were measured by enzyme-linked immunosorbent assay.The pathomorphological changes of spinal nerve roots were observed by hematoxylin-eosin(HE)staining;quantitative reverse transcription polymerase chain reaction was used to detect iNOS mRNA expression in spinal nerve roots;the NF-κB and iNOS protein expression in spinal nerve roots was detected by the immunofluorescence method.Results:Compared with the sham operation group,the threshold of paw withdrawal pain in the model group was decreased,and the expression levels of serum NF-κB,iNOS,and NO were increased;HE staining showed many degenerated and dissolved Schwann cells in spinal nerve roots with vacuolar changes;meanwhile,the expression levels of NF-κB and iNOS proteins,and the iNOS mRNA in spinal nerve roots were increased.Compared with the model group,the paw withdrawal pain thresholds in acupuncture group 1 and acupuncture group 2 were increased,and the increase in acupuncture group 2 was greater(P<0.05);the expression levels of serum NF-κB,iNOS,and NO in acupuncture group 1 and acupuncture group 2 were decreased,especially in acupuncture group 2(P<0.01);the vacuolar changes of spinal nerve roots,and the degeneration and lysis of Schwann cells in acupuncture group 1 and acupuncture group 2 were decreased,which were more obvious in acupuncture group 2;the NF-κB and iNOS protein expression and the iNOS mRNA expression levels in spinal nerve roots of acupuncture group 1 and acupuncture group 2 were decreased,especially in acupuncture group 2(P<0.01).Conclusion:Acupuncture at Houxi(SI3)and Huantiao(GB30)can improve the morphology of spinal nerve roots,inhibit the NF-κB and iNOS protein expression levels in spinal nerve roots and the serum NO level,and relieve the pain caused by inflammation of spinal nerve roots,which may be one of the mechanisms of acupuncture in LDH treatment.

Effects of sparrow-pecking moxibustion on the temperature and blood flow perfusion of moxibustion point area and uterus and serum AVP,PGF2α,and TXB2 in rats with dysmenorrhea / 针灸推拿医学（英文版）

Objective:To observe the effects of sparrow-pecking moxibustion at Shenque(CV8)and Guanyuan(CV4)on the writhing reaction and score,the temperature and blood flow perfusion of moxibustion point area and uterus,the serum levels of arginine vasopressin(AVP),prostaglandin(PG)F2α,and thromboxane(TX)B2 in rats with primary dysmenorrhea(PD)due to cold-dampness stagnation,and to explore the possible mechanism of sparrow-pecking moxibustion in treating PD.Methods:Thirty-two healthy non-pregnant female Wistar rats were randomly divided into a normal group,a model group,an ibuprofen group,and a sparrow-pecking moxibustion group,with 8 rats in each group.Except for the normal group,the other three groups were subjected to modeling with cold water bath combined with estradiol benzoate and oxytocin injection.Rats in the sparrow-pecking moxibustion group were treated with sparrow-pecking moxibustion at Shenque(CV8)and Guanyuan(CV4)on the 8th day of modeling,30 min/time,once a day for 3 d;those in the ibuprofen group were treated with 0.8 mL ibuprofen solution(a specification of 125 mg in 10 mL)on the 8th day of modeling,once a day for 3 d;those in the normal group and the model group were given 0.8 mL normal saline,once a day for 3 d.On the 11th day,rats in each group were intraperitoneally injected with oxytocin(2 U/rat),and the writhing incubation period and writhing score in 20 min were observed;the temperature and the blood perfusion of Shenque(CV8),Guanyuan(CV4),and uterus in vivo were detected;the serum levels of AVP,PGF2α,and TXB2 were determined.Results:The writhing incubation period was significantly longer(P<0.01)and the writhing score was significantly lower(P<0.01)in the sparrow-pecking moxibustion group and the ibuprofen group than in the model group;compared with the ibuprofen group,the writhing incubation period was prolonged(P<0.01)and the writhing score was decreased(P<0.01)in the sparrow-pecking moxibustion group;compared with the normal group,the temperature and the blood perfusion of Shenque(CV8),Guanyuan(CV4),and uterus were significantly decreased,while the serum PGF2α,AVP,and TXB2 levels were significantly increased(P<0.01)in the model group;compared with the model group,the temperature and the blood perfusion of Shenque(CV8),Guanyuan(CV4),and uterus were significantly increased,and the serum levels of PGF2α,AVP,and TXB2 were significantly decreased in the ibuprofen group and the sparrow-pecking moxibustion group(P<0.05 or P<0.01);compared with the ibuprofen group,the temperature and the blood perfusion of Shenque(CV8),Guanyuan(CV4),and uterus were significantly increased(P<0.05),the serum AVP and TXB2 levels were significantly decreased(P<0.05),while the serum PGF2α level had no statistical difference in the sparrow-pecking moxibustion group(P>0.05).Conclusion:Sparrow-pecking moxibustion had a remarkable analgesic effect on the rats with PD due to cold-dampness stagnation,and the mechanism may be related to the increased temperature and blood perfusion of the moxibustion point area and uterus,as well as the decreased serum PGF2α,AVP,and TXB2 levels.

LRG1 inhibits hepatic macrophage activation by enhancing TGF-β1 signaling to alleviate MAFLD in mice / 南方医科大学学报

OBJECTIVE@#To explore the effect of leucine-rich α-2-glycoprotein (LRG1) derived from hepatocytes on activation of hepatic M1 Kupffer cells.@*METHODS@#A metabolic dysfunction-associated fatty liver disease (MAFLD) model was established in BALB/c mice by high-fat diet (HFD) feeding for 16 weeks. Oleic acid was used to induce steatosis in primary cultures of mouse hepatocytes. The mRNA and protein expressions of LRG1 in mouse liver tissues and hepatocytes were detected by real-time PCR and Western blotting. Primary hepatic macrophages were stimulated with the conditioned medium (CM) from steatotic hepatocyte along with LRG1 or transforming growth factor-β1 (TGF-β1), or both for 24 h, and the expression levels of inducible nitric oxide synthase (iNOS) was detected with Western botting, and the mRNA expressions of iNOS, chemokine ligand 1 (CXCL-1) and interleukin-1β (IL-1β) were measured by RT-PCR. The MAFLD mice were injected with LRG1 (n=6), TGF-β1 (n=6), or both (n=6) through the caudal vein, and the live tissues were collected for HE staining and immumohistochemical detection of F4/80 expression; the mRNA expressions of iNOS, CXCL-1 and IL-1β in liver tissues were detected using RT-PCR.@*RESULTS@#The mRNA and protein expression levels of LRG1 were significantly downregulated in the liver tissues of MAFLD mice and steatotic hepatocytes (P < 0.05). Treatment of the hepatic macrophages with CM from steatosis hepatocytes significantly enhanced the mRNA expression levels of iNOS, CXCL-1 and IL-1β, and these changes were significantly inhibited by the combined treatment with TGF-β1 and LRG1 (P < 0.05). In MAFLD mice, injections with either LRG1 or TGF-β1 alone reduced hepatic lipid deposition and intrahepatic macrophage infiltration, and these effects were significantly enhanced by their combined treatment, which also more strongly inhibited the mRNA expression levels of iNOS, CXCL-1 and IL-1β (P < 0.05).@*CONCLUSION@#LRG1 inhibits hepatic macrophage infiltration by enhancing TGF-β1 signaling to alleviate fatty liver inflammation in MAFLD mice.