ObjectiveTo explore the expression of N-cadherin and β-catenin mRNA in human brainstem and supratentorial gliomas. MethodsN-cadherin and β-catenin mRNA expression in 18 cases of brainstem gliomas and 18 cases of supratentorial gliomas tissues were detected with PT-PCR. Resultsβ-catenin mRNA expression was more in human brainstem gliomas than in supratentorial gliomas （t=2.255,P<0.05）, but was not significantly different of N-cadherin mRNA (P＞0.05). The expression of N-cadherin mRNA in human brainstem gliomas of grades Ⅰ～Ⅱ were less than those in human gliomas of grades Ⅲ～Ⅳ (t=2.711，P<0.05), but was not of β-catenin mRNA (P＞0.05). N-cadherin mRNA expression was positively correlated with the β-catenin mRNA expression in either brainstem gliomas or supratentorial gliomas （r=0.480，r=0.809 respectively, P<0.05）. ConclusionThe over expressions of N-cadherin and β-catenin may play an important role in the invasion and malignant progress of human brainstem gliomas.

Objective To assess and optimize the dosage regimens of nor-vancomycin in patients with different renal functions.Methods The minimum inhibitory concentration ( MIC ) distribution was determined by agar dilution method with the target value of AUC 0-24/MIC≥638.Ten thousand cases in virtue of Monte Carlo simulation were performed in dif-ferent doses to obtain probabilities of target attainment ( PTA) and cumu-lative fractions of response ( CFR ) in patients with different renal func-tions.Results For the patients with normal renal function , when En-terococcus faecium and Enterococcus faecalis were treated with recommen-ded dose , from 0.8 to 1.6 g· d-1 , the CFR were lower than 59.77%.The CFR could reach to 83.95%and 73.10%when the dose was adjus-ted to 2.5 g· d -1.For the patients with moderate renal function insuffi-ciency , the CFR could reach to 82.81% at the dose of 0.8 g · d -1 against Enterococcus faecalis.The CFR could reach from 73.10% to 86.84%at the dose from 0.8 to 2.5 g · d-1 in the process of treating Enterococcus faecium.For the patients with severe renal function insuffi-ciency , the CFR could reach to 97.77% and 85.90% respectively a-gainst Enterococcus faecalis and Enterococcus faecium.Conclusion Monte Carlo simulation provides dosage regimens and the norvancomycin regimen is complemented and optimized.

Adenine ; analogs & derivatives ; therapeutic use ; Adolescent ; Adult ; Aged ; Creatinine ; blood ; Female ; Hepatitis B, Chronic ; blood ; drug therapy ; Humans ; Male ; Middle Aged ; Organophosphonates ; therapeutic use ; Phosphorus ; blood ; Retrospective Studies ; Young Adult

BACKGROUNDStudies have shown that abnormal activation of the sonic hedgehog pathway is closely related to tumorigenesis in central nervous system. This study aimed to investigate the role of the sonic hedgehog signaling pathway in the occurrence of brainstem and supratentorial glioma.

METHODSReal-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry were used to detect the expression of sonic hedgehog-related components in 5 specimens of normal brain tissue, 10 of grade II brainstem glioma, and 10 of grade II supratentorial glioma. The significance of differences between two groups was determined using the Mann-Whitney U test or the two-sample test according to the results of normality distribution tests.

RESULTSThe mRNA expression levels of sonic hedgehog-related genes were higher in brainstem astrocytomas than in supratentorial astrocytomas and normal brain tissue. The level of protein patched homolog 1 (PTCH1) was significantly higher in brainstem astrocytomas than in supratentorial astrocytomas and normal brain tissue (P < 0.01). Immunohistochemistry semi-quantitative analysis was consistent with the qRT-PCR result that PTCH1 expression was increased significantly in brainstem astrocytomas at the protein level (P < 0.05).

CONCLUSIONSEnhanced PTCH1 expression and activation of the sonic hedgehog pathway are involved in brainstem glioma. This may be related to the difference in malignant biological behavior between brainstem and hemispheric glioma, and could be an ideal therapeutic target in brainstem glioma.

Adolescent ; Adult ; Astrocytoma ; genetics ; metabolism ; Brain Stem Neoplasms ; genetics ; metabolism ; Female ; Glioma ; genetics ; metabolism ; Hedgehog Proteins ; genetics ; metabolism ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Patched Receptors ; Patched-1 Receptor ; Real-Time Polymerase Chain Reaction ; Receptors, Cell Surface ; genetics ; metabolism ; Signal Transduction ; genetics ; physiology ; Supratentorial Neoplasms ; genetics ; metabolism ; Young Adult

BACKGROUND:For the replacement treatment of long-segment tracheal defects,although tissue engineering research has made some progress in recent years,it is still not perfect,and one of the biggest difficulties is that the hemodynamic reconstruction of the tracheal replacement cannot be achieved rapidly. OBJECTIVE:To preliminarily explore the potential of polycaprolactone scaffolds modified with exosome-loaded hydrogels to construct a rapidly vascularized tracheal substitute. METHODS:Exosomes were extracted from bone marrow mesenchymal stem cells of SD rats.After preparation of hyaluronic acid methacrylate solution,the exosome solution was mixed with hyaluronic acid methacrylate solution at a volume ratio of 1:1.Hyaluronic acid methacrylate hydrogels loaded with exosomes were prepared under ultraviolet irradiation for 5 minutes.The degradation of exosome-unloaded hydrogels and the controlled release of exosome-loaded hydrogels were detected.Polycaprolactone scaffolds were prepared by 3D printing.The pure hyaluronic acid methacrylate solution and the exosome-loaded hyaluronic acid methacrylate solution were respectively added to the surface of the scaffold.Hydrogel-modified scaffolds and exosome-modified scaffolds were obtained after ultraviolet irradiation.Thirty SD rats were randomly divided into three groups with 10 rats in each group and subcutaneously implanted with simple scaffolds,hydrogel-modified scaffolds and exosome-modified scaffolds,respectively.At 30 days after surgery,the scaffolds and surrounding tissues of each group were removed.Neovascularization was observed by hematoxylin-eosin staining and Masson staining and the expression of CD31 was detected by immunofluorescence. RESULTS AND CONCLUSION:(1)As time went by,the hydrogel degraded gradually,and the exosomes enclosed in the hydrogel were gradually released,which could be sustained for more than 30 days.The exosome release rate was faster than the degradation rate of the hydrogel itself,and nearly 20%of the exosomes were still not released after 30 days of soaking.(2)Under a scanning electron microscope,the surface of the simple polycaprolactone scaffold was rough.After hydrogel modification,a layer of gel was covered between the pores of the scaffold,and the scaffold surface became smooth and dense.(3)After 30 days of subcutaneous embedding,hematoxylin-eosin staining and Masson staining showed that more neovascularization was observed inside the scaffolds of the exosome-modified scaffold group compared with the hydrogel-modified scaffold group.The hydrogels on the scaffolds of the two groups were not completely degraded.Immunofluorescence staining showed that CD31 expression in the exosome-modified scaffold group was higher than that in the hydrogel-modified scaffold group(P<0.000 1).(4)These results indicate that hyaluronic acid methacrylate hydrogels can be used as controlled-release carriers for exosomes.The 3D-printed polycaprolactone scaffold modified by hyaluronic acid methacrylate hydrogel loaded with exosomes has good biocompatibility and has the potential to promote the formation of neovascularization.

Objective To investigate clinical effect of tendons pulling,poking and kneading for the treatment of external humeral epicondylitis.Metods From January 2018 to December 2021,a multicenter randomized controlled study was per-formed to collect 192 patients with external humeral epicondylitis in Wangjing Hospital,Beijing Dianli Hospital,and Beijing Fengsheng Osteotraumatology Hospital,respectively,and they were divided into treatment group and control group by random number table method.There were 96 patients in treatment group,including 36 males and 60 females,aged from 28 to 60 years old with an average of(41.20±5.50)years old;the course of disease ranged from 1 to 14 days with an average of(5.24±1.35)days;they were treated once every other day for 2 weeks.There were 96 patients in control group,including 33 males and 63 females,aged from 26 to 60 years old with an average of(43.35±7.75)years old;the course of disease ranged from 1 to 14 days with an average of(5.86±1.48)days;they were treated with topical voltaalin combined with elbow joint fixation for 2 weeks.Visual analogue scale(VAS)and Hospital for Surgery Scoring System(HSS)elbow pronation and supination angles,wrist metacarpal flexion and dorsal extension angles,elbow tenderness between two groups were compared before treatment and at 1,3,5,7,11 and 13 days after treatment;Hospital for Surgery Scoring System 2(HSS2)was compared before treatment and the final treatment.Results All patients were followed up for 10 to 14 days with an average of(12±1.6)days.VAS between treatment group and control group before treatment were 6.83±1.36 and 6.79±1.58,respectively,and decreased to 1.49±1.09 and 2.11±1.81 after the final treatment.VAS of treatment group were significantly lower than those of control group at 1,3,5,7,9,11 and 13 days after treatment(P＜0.05).HSS between two groups were 61.73±11.00 and 36.47±12.45 before treatment,respectively,and increased to 94.42±5.9 and 91.44±9.11 at the final treatment.HSS of treatment group were signifi-cantly higher than those of control group at 1,3,5,7,9,11 and 13 days after treatment(P＜0.05).On the 5th day after treat-ment,the external and internal rotation angles of elbow in treatment group were(66.41±12.69)° and(66.35±13.54)°,while those in control group were(62.08±16.03)° and(61.77±16.35)°.On the 7th day after treatment,the external and internal ro-tation angles of elbow were(69.79±12.64)° and(70.02±13.55)° in treatment group,and(65.28±15.86)° and(65.09± 16.67)° in control group.Elbow joint motion in treatment group was higher than that in control group(P＜0.05).On the 5th day after treatment,angles of wrist dorsiflexion and palm flexion were(39.43±15.94)°and(46.68±11.10)° in treatment group,and(38.51±18.49)° and(44.27±13.58)° in control group.On the 7th day after treatment,angles of wrist dorsiflexion and palm flexion were(42.52±16.50)° and(49.23±10.96)° in treatment group,and(41.18±20.09)° and(46.64±14.63)° in control group.The motion of wrist joint in treatment group was higher than that in control group(P＜0.05).On the 13th day after treatment,HSS2 in treatment group 93.61±6.32 were higher than those in control group 92.06±7.94(P＜0.05).There was no significant difference in elbow tenderness between two groups at each time point(P＞0.05).Conclusion Voltaren external treatment combined with elbow fixation and tendons pulling,poking and kneading could effectively improve symptoms of exter-nal humeral epicondylitis.Compared with voltaren external treatment,tendons pulling,poking and kneading has advantages of longer analgesic time and better elbow function recovery.

OBJECTIVELyme disease and Human granulocytic anaplasmosis are tick-borne diseases caused by Borrelia burgdorferi and Anaplasma phagocytophilum respectively. We have investigated infection and co-infection of the two diseases in the population of forest areas of eight provinces in China by measuring seroprevalence of antibodies against B. burgdorferi and A. phagocytophilum.

METHODSForest areas in 8 provinces were chosen for investigation using whole sampling and questionnaire survey methods. 3 669 serum samples from people in the forest areas were tested for the presence of antibodies by indirect immunofluorescent assay (IFA).

RESULTSSeroprevalence against B. burgdorferi was 3% to 15% and against A. phagocytophilum was 2% to 18% in the study sites in the 8 provinces in China. We also found co-infection of B. burgdorferi and A. phagocytophilum in 7 of the 8 provinces (the exception being the Miyun area in Beijing). The seroprevalence for both B. burgdorferi and A. phagocytophilum was significantly higher among people exposed to ticks than among people who were not exposed to ticks.

CONCLUSIONWe conclude that both pathogens are endemic in the forest areas in the eight provinces, but the prevalence of B. burgdorferi and A. phagocytophilum differs between the provinces.

Adolescent ; Adult ; Anaplasma phagocytophilum ; pathogenicity ; Anaplasmosis ; blood ; epidemiology ; Animals ; Borrelia burgdorferi ; pathogenicity ; Child ; China ; Coinfection ; Female ; Humans ; Lyme Disease ; blood ; epidemiology ; Male ; Middle Aged ; Seroepidemiologic Studies ; Tick-Borne Diseases ; blood ; epidemiology ; Trees ; Young Adult

Objective:To study the life characteristics and related risk factors of patients with depression in Shandong Province.Methods:Based on the 2015 mental epidemiological survey database in Shandong Province,a total of 832 patients with depression,807 high-risk individuals with depression,and 819 low-risk individuals were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ)and the Structured Clinical Interview for DSM-Ⅳ-TR Axis I Disorders,Research Version(SCID-I/P).In 2020,SCID-I/P was used for re diagnosis,and the General Health Questionnaire(GHQ-12),Simple Quality of Life question-naire,Pittsburgh sleep quality index(PSQI),Childhood Trauma Questionnaire(CTQ),Social Support Rating Scale(SSRS),Global Pain Scale(GPS),Montreal Cognitive Assessment(MoCA),Simplified Coping Style Question-naire(SCSQ)were used for evaluation.Compare changes in the quality of life of depression patients and construct a risk factor model.Results:Patients with depression had lower scores on the simple quality of life questionnaire at baseline and at retest after 5 years than those in the high-and low-risk groups,those in remission of depression had higher scores on the simple quality of life questionnaire at baseline and at retest after 5 years than those in non-re-mission,and those with new-onset disorder in the high-and low-risk groups had lower scores on the simple quality of life questionnaire at baseline and at retest after 5 years than those with no-onset disorder(Ps＜0.001).Depres-sion diagnosis and PSQI scale scores at baseline negatively predicted at retest after 5 years(β=-0.06,-0.15),while coping style tendencies at baseline positively predicted(β=0.06).The simple quality of life questionnaire at baseline negatively predicted depression diagnosis at retest after 5 years,GHQ-12 scores at retest after 5 years,and PSQI scale scores at retest after 5 years(β=-0.11,-0.17,-0.09),while the simple quality of life question-naire at baseline positively predicted coping style tendencies at retest after 5 years(β=0.13).Depression diagnosis at retest after 5 years,GHQ-12 scores at retest after 5 years,PSQI scale scores at retest after 5 years,coping style tendencies at retest after 5 years,SSRS scale scores,CTQ scale scores,GPS scale scores,and the simple quality of life questionnaire at baseline all influenced the simple quality of life questionnaire at retest after 5 years through ei-ther direct or indirect pathways.Conclusion:It suggest that the quality of life is lower in patients with depression than in the general population.Depression diagnosis,sleep,mental health,pain,social support,childhood trauma and coping are direct and indirect risk factors affecting life.

Objective To understand the unhealthy related behaviors of echinococcosis patients in Tibetan region in Sich-uan Province,so as to provide the references for the health education of echinococcosis.Methods The echinococcosis patients who were registered in the Tibetan region in Sichuan Province were selected as target population. The basic situation and un-healthy related behaviors of them were surveyed by individual interviews.Results Totally 368 echinococcosis patients were in-vestigated.The proportion of patients who lived with dogs was 53.3%,who did not wash hands before meals was 23.4%,who ate raw food was 15.5%,who fed dogs with diseased livestock visceral organs was 9.8%,who drank unboiled water was 8.7%,and who played with dogs was 5.4%.The proportion of nomads'unhygienic behaviors was higher than that of sedentary residents'un-hygienic behaviors.The proportion of playing with dogs and feeding dogs with diseased livestock visceral organsin students was higher than that in nomads.Conclusion There are some unhealthy related behaviors in echinococcosis patients in Garzê Prefec-ture,and the different health education modes for echinococcosis patients with different characteristics should be applied.

OBJECTIVE: To explore the mechanism of nuclear factor-kappa B (NF-κB), phosphatidylinositol 3-kinase (PI3K)/protein kinase B(PKB/Akt) and mitogen-activated protein kinase (MAPK) signaling pathways after intervention of advanced glycosylation end products (AGEs) in peripheral blood mononuclear cells (PBMCs) and osteoblasts (OB) in rats, so as to provide certain experimental basis and theoretical basis for further research on the clinical treatment of periodontal tissue inflammation caused by diabetes mellitus. METHODS: AGEs were prepared, PBMCs and OB were isolated and cultured in vitro. CCK-8 was used to detect the cell viability intervened by different concentrations and time of AGEs. Western blot and qRT-PCR were used to detect the expression changes of genes related to NF-κB, PI3K/PKB and MAPK signaling pathways. RESULTS: OB and PBMCs were successfully isolated and cultured in vitro. The activity of PBMCs and OB cells was significantly correlated with the concentration, time and interaction of AGEs. With the increase of AGEs concentration and time, the activity of PBMCs and OB cells significantly decreased (P < 0.001). AGEs stimulation significantly increased the expression of NF-κB in PBMCs and the contents of tumor necrosis factor α(TNF-α), interleukin-1β(IL-1β) (P < 0.01). TNF-α, IL-1β levels were significantly reduced after inhibition of NF-κB pathway (P < 0.01). NF-κB p65, JNK, and p38 phosphorylated and non-phosphorylated proteins increased significantly after AGEs stimulation of OB (P < 0.05). The phosphorylated protein expression of IκB was significantly increased, while the expression of non-phosphorylated protein was decreased (P < 0.01).The expressions of NF-κB p65, JNK, and IκB were significantly increased at the mRNA levels, and the expressions of IκB mRNA were significantly decreased (P < 0.05). There was no difference in the expression of Akt in either phosphorylated or non-phosphorylated proteins or at the mRNA level (P>0.05). With the addition of MAPK signaling pathway inhibitors, the phosphorylation and non-phosphorylated protein expressions of NF-κB p65, p38 and JNK were significantly reduced, and the phosphorylated protein of IκB was significantly decreased and the non-phosphorylated protein was significantly increased compared with the group with AGEs alone (P < 0.05). The results of qRT-PCR showed that the expression of IκB increased significantly after the addition of the JNK pathway blocker (P < 0.05), and the expression of NF-κB p65, p38 and JNK decreased, but the difference was not significant (P>0.05). While NF-κB p65, p38 and JNK were significantly decreased and IκB was significantly increased in the AGEs group after the addition of the p38 pathway blocker (P < 0.05). At this time, there was still no significant change in the expression of Akt at the protein level and mRNA level (P>0.05). CONCLUSION AGEs inhibit the proliferation of PBMCs and OB, and the NF-κB and MAPK pathways are likely involved in regulating this process, but not the PI3K/PKB pathway.
Animals ; Cell Proliferation ; Glycation End Products, Advanced ; Leukocytes, Mononuclear ; NF-kappa B ; Osteoblasts ; Phosphatidylinositol 3-Kinases ; Rats ; Tumor Necrosis Factor-alpha ; p38 Mitogen-Activated Protein Kinases