Objective:To analyse the relationship of ultrastructural changes of glomerular basement membrane (GBM) and glomerular distributions of laminin α1 and laminin α5 in patients with Alport' s syndrome. Methods: Twenty patients with Alport' s syndrome were recruited. The thickness of GBM and the extension of thickening and splitting GBM were measured under transmission electron microscope. Normal renal tissues from 6 nephrectomies of renal carcinoma were taken as controls. Paraffin embedded sections of formalin-fixed renal tissue were processed for immunohistochemistry with monoclonal antibodies to laminin α1 and laminin α5. Their distributions in GBM were evaluated by a semiquantitative scale of positive extension; absent, 0≤25% , 1; 25%-50% , 2; 50%-75% , 3;≥75% , 4. Results: There were a variety of degrees of thickening or splitting GBM in patients with Alport' s syndrome. Laminin al was positive in glomerular mesangial area and absolutely negative in GBM and laminin α5 was evenly positive in GBM in normal tissue. In Alport' s syndrome, laminin α1 was much weaker in glomerular mesangial area, but strongly positive in GBM; laminin α5 in GBM was prominently reduced. There was a high negative correlation of semiquantitative scores between laminin al and laminin α5 (r =-0. 83, P＜0. 001). The extension of thickening or splitting GBM was positively correlated with scores of laminin al in GBM ( r = 0. 76, P＜0.001; r = 0. 56, P=0. 015 ) , and was negatively correlated with scores of laminin α5 in GBM ( r =-0. 59, P =0. 010; r=-0. 53, P =0.025). Conclusion: Abnormal distribution of laminin al and laminin α5 in GBM is correlated with GBM thickening and splitting in human Alport' s syndrome.

Objectlve To investigate the inhibition of Coxsackievirus B3(CVB3)infection in cardiac myocytes cultured by small interfering RNA(siRNA)-mediated RNA interference and to evaluate the feasibility of siRNA as the prophylaxis and therapy for CVB3 infection.Methods Cardiac myocytes were prepared in vitro and infected with CVB3,and transfected with siRNA by lipofectamin and electroporation.The numbers of beating cardiac myocytes were counted under the microscope.Neutral red staining was used to evaluate the mortality of cardiac myocytes.Antiviral activities of these siRNAs were estimated by observing cytopathic effect(CPE),plaque reduction assay,Western blot assay and RT-PCR.Results siRNA-3753,which aimed at sequence in 2B section of CVB3 genome,displayed a stronger inhibition of CVB3 infection through screening in HeLa cells,siRNA-3753,chosen to transfect cultured neonatal mice cardiac myocytes,Wag observed to keep a good states of growing and beating at 24 h after CVB3 infection.Whereas the cytopathic signature of controlled cells became stopping beating,round and finally the cell fell off the culture plate.The results showed that siRNA-3753 could protect cells significantly,98.1%inhibition of CVB3 replication with electroporation transfection and 78.2%inhibition of CVB3 with liposome transfection.Transfection efficiencies were 56.0 3%and 9.0%by electroporation and lipofectamin,respectively.Conclusion siRNA,which aims at sequence in 2B section of CVB3 genome,can inhibit CVB3 infection in cultured cardiac myocytes.

OBJECTIVETo compare the levels of STAT4 tyrosine phosphorylation in peripheral T-lymphocytes induced by IL-12 in rheumatoid arthritis (RA) and osteoarthritis (OA).

METHODSFrom May 2007 to August 2009, peripheral blood mononuclear cells (PBMCs) were isolated from RA patients [RA group, all the cases were female, the age was from 28 to 55 years with an average of (45.0 +/- 13.0) years] and OA patients [OA group, all the cases also were female; the age was from 55 to 75 years with an average of (67.0 +/- 9.6) years]. The purity of T-lymphocytes from PBMCs was accredited by flow cytometry. The IL-12 of 50 ng/ml added in T-lymphocytes, the levels of STAT4 tyrosine phosphorylation were detected by western blot after different time intervals (0, 10, 30, 60 min).

RESULTSThe purity of T-lymphocytes were above 91% through diremption and depuration for peripheral blood monouclear cells. The levels of STAT4 tyrosine phosphorylation in T-lymphocytes from RA induced by IL-12 were higher than that from OA in the different times (10, 30, 60 min); after 30 min, its levels from RA and OA achieved to crest value.

CONCLUSIONSTAT4 in peripheral T-lymphocytes of rheumatoid arthritis was more easily to be activated than osteoarthritis.

Adult ; Aged ; Arthritis, Rheumatoid ; immunology ; Female ; Humans ; Interleukin-12 ; pharmacology ; Middle Aged ; Osteoarthritis ; immunology ; Phosphorylation ; Polymorphism, Single Nucleotide ; STAT4 Transcription Factor ; genetics ; metabolism ; T-Lymphocytes ; drug effects ; metabolism ; Tyrosine ; metabolism

Acute altitude reaction is a stress response of organism to special altitude environmental factors such as hypoxia, low pressure, cold, dry and strong ultraviolet. As it is the most incident disease in high altitude areas, its prevention remains a problem to be solved. In China, the traditional Chinese (Tibetan) medicines have been recognized as an effective means of preventing and treating acute altitude sicknesses. Some single-recipe or compound traditional Chinese (Tibetan) medicines have been proved to be effective for acute altitude sicknesses. In this article, we will describe traditional Chinese (Tibetan) medicines of different types with efficacy in prevention and treatment of altitude sicknesses.
Acute Disease ; Altitude Sickness ; drug therapy ; prevention & control ; Humans ; Medicine, Chinese Traditional ; Medicine, Tibetan Traditional

OBJECTIVETo observe the effect of Qubi Recipe (QR) on the expression of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and hypoxia-inducible factor (HIF)-1alpha in rats with type II collagen-I induced arthritis (CIA), and to explore its therapeutic roles and mechanism.

METHODSTotally 72 male SD rats of SPF grade were recruited. Twelve were randomly selected as the blank control group. The CIA model was established in the rest 60 rats by subcutaneously injecting type II collagen of bovine emulsion from the tail root and induction of incomplete Freund's adjuvant. On day 15 after primary immunization rats were randomly divided into four groups, i.e., the CIA model group, the Tripterygium Glycosides (TG) group (at the daily dose of 9.68 mg/kg body weight), the high dose QR group (at the daily dose of 6.66 g/kg body weight), and the low dose QR group (at the daily dose of 3.33 g/kg body weight), 15 in each group. Corresponding medication was given to rats in all groups by gastrogavage once daily for 4 successive weeks. An equal volume of pure water was given to rats in the blank control group and the CIA model group by gastrogavage, once daily for 4 successive weeks. The swelling degree of the joints was measured. Rats were sacrificed after 4-week treatment. Plasma levels of SOD, MDA, and GSH-Px were measured with colorimetric method. The expression of HIF-1alpha was detected by immunohistochemistry.

RESULTS(1) Compared with the CIA model group, the swelling degree of the joints was significantly alleviated in the TG group and the high dose QR group (P < 0.01, P < 0.05), and it was obviously milder in the high dose QR group than in the TG group (P < 0.05). (2) Compared with the CIA model group, the activities of GSH-Px could be obviously elevated and activities of MDA lowered in the TG group, the high dose QR group, and the low dose QR group (P < 0.05). Plasma activities of SOD could be obviously elevated in the high dose QR group and the TG group (P < 0.05). (3) Compared with the CIA model group, the expression of HIF-1alpha obviously decreased in the TG group and the high dose QR group (P < 0.05), and it showed a decreasing tendency in the low dose QR group with no statistical difference (P > 0.05).

CONCLUSIONSQR could markedly alleviate the swelling degree of ankle joints in CIA model rats. Its therapeutic efficacy was superior to that of TG. Its mechanism might be achieved through down-regulating expression of HIF-1alpha in the joint, and regulating activities of SOD, MDA and GSH-Px in the plasma.

Animals ; Arthritis, Experimental ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Glutathione Peroxidase ; blood ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Joints ; metabolism ; pathology ; Male ; Malondialdehyde ; blood ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Superoxide Dismutase ; blood

Objective: To compare bioelectrical impedance analysis (BIA) and dual energy X ray absorptiometry (DXA) for measuring body mineral content (BMC) of children and adolescents, and to provide a basis for BIA to accurately measure BMC in children and adolescents. Methods: By using the convenience sampling method, among 1 469 children and adolescents aged 7-17 were recruited in Guangzhou from April to May 2019, the BMC was measured by DXA and BIA. The intraclass correlation coefficient ( ICC ) and Bland Altman analysis were used to evaluate the agreement between BIA and DXA. Bland Altman analysis was performed on log transformed data. The BMC was categorized into age and specific tertiles, and the agreement between methods was evaluated based on the kappa coefficients. Treating the BMC with DXA as the dependent variable, a prediction model was constructed for correcting the BIA measure. Results: The ICC s were 0.93 and 0.94 for boys and girls, respectively. In Bland Altman analysis, the limits of agreements for the BIA to DXA ratio were wide in boys and girls, ranging from 0.27-0.76 and 0.17-0.72, respectively. The kappa coefficients for categorized BMC levels were 0.57 and 0.45 for boys and girls, respectively, showing a fair to good degree of agreement. When sub grouped by BMI, the kappa coefficients for all BMI groups of boys and overweight girls were all >0.75 , with an excellent agreement. The prediction models for boys and girls were as follows: BMC DXA =-0.51+0.44× BMC BIA + 0.06× Age +0.02× BMI ; and BMC DXA =-0.55+0.43× BMC BIA +0.06× Age +0.02× BMI , respectively. The R 2 for models of boys and girls were 0.87 and 0.87, respectively. Conclusion The agreement between BIA and DXA was poor for measuring BMC, but acceptable when evaluating the categorized BMC levels, suggesting the BIA may be applied in assessment of the BMC levels when compared to the age and gender specific population. Additionally, the prediction model for correcting BMC by BIA fis well to the measurement by DXA.

OBJECTIVETo investigate the lymph node metastasis and its risk factors in T1-2 staging invasive rectal carcinoma.

METHODSThe data of 1116 patients with rectal cancer treated with total mesorectal excision (TME) technique from January 2000 to April 2009 was analyzed retrospectively. The clinicopathological factors analyzed included gender, age, primary symptom type, number of symptoms, duration of symptom, synchronous polyps, preoperative serum carcino-embryonic antigen level, preoperative serum CA19-9 level, the distance of tumor from the anal verge, tumor size, tumor morphological type, tumor circumferential extent, tumor differentiation and tumor T staging. Statistical analysis was performed by using Logistic regression analysis and Chi-square test.

RESULTSA total of 1116 patients were enrolled, and 358 cases (32.1%) were classified as with T1-2 staging tumor. Two cases (5.6%, 2/36) in patients with a T1 staging tumor were found with lymph node metastasis, and 75 cases (23.3%, 75/322) in patients with a T2 staging tumor, respectively. Compared with patients with T3-4 staging tumor, lymph node metastasis rate of the patients with T1-2 staging tumor was significantly lower [21.5% (77/358) vs. 51.6% (391/758), P < 0.05]. Only the tumor T staging was found as the independent risk factor for the lymph node metastasis in patients with T1-2 staging tumor on multivariate Logistic regression analysis (odds ratio: 5.162; 95%CI: 1.212 to 21.991; P = 0.026).

CONCLUSIONSA substantial proportion of T1-2 staging rectal cancers harbor metastatic lymph nodes and the clinicopathological features except for T staging fail to predict the lymph node metastasis. Further research is warranted to identify the risk factors and guide the clinical practice in patient with T1-2 staging tumor.

Female ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Rectal Neoplasms ; pathology ; Retrospective Studies ; Risk Factors

OBJECTIVETo investigate the clinical and genetic features of two families with late-onset glutaric aciduria type II caused by ETFDH mutations.

METHODSTarget gene sequence capture and next generation sequencing were used for sequencing of suspected patients and their family members. The patients' clinical features were retrospectively analyzed and literature review was performed.

RESULTSThe probands of the two families had a clinical onset at the ages of 10 years and 5.5 years respectively, with the clinical manifestations of muscle weakness and muscle pain. Laboratory examinations revealed significant increases in the serum levels of creatine kinase, creatine kinase-MB, and lactate dehydrogenase. Tandem mass spectrometry showed increases in various types of acylcarnitines. The analysis of urine organic acids showed an increase in glutaric acid. Electromyography showed myogenic damage in both patients. Gene detection showed two novel mutations in the ETFDH gene (c.1331T>C from the mother and c.824C>T from the father) in patient 1, and the patient's younger brother carried the c.1331T>C mutation but had a normal phenotype. In patient 2, there was a novel mutation (c.177insT from the father) and a known mutation (c.1474T>C from the mother) in the ETFDH gene. Several family members carried such mutations. Both patients were diagnosed with glutaric aciduria type II. Their symptoms were improved after high-dose vitamin B2 treatment.

CONCLUSIONSFor patients with unexplained muscle weakness and pain, serum creatine kinase, acylcarnitines, and urinary organic acids should be measured, and the possibility of glutaric aciduria type II should be considered. Genetic detection is helpful to make a confirmed diagnosis.

Child ; Computational Biology ; Electron-Transferring Flavoproteins ; genetics ; Female ; Humans ; Iron-Sulfur Proteins ; genetics ; Male ; Multiple Acyl Coenzyme A Dehydrogenase Deficiency ; drug therapy ; genetics ; Mutation ; Oxidoreductases Acting on CH-NH Group Donors ; genetics

Angelica sinensis(Umbelliferae)is a worldwide-known medicinal plant and also a famous traditional Chinese medicinal herb. It is recorded to possess the efficacy of enriching the blood and invigorating the circulation of blood of the individual.Danggui was extensively applied to the treatment of gynecological disorders. Modern researches indicate that phthalides are main chemical components related to the bioactivities of A.sinensis, such as anti-tumor, analgesic and neuroprotective effect.The advances in studies on the structures and pharmacological activities of phthalides from A.sinensis are reviewed to provide references for further researches and utilization of their medicinal value.

Objective To analysis the current situation of hospitalized patients seeking medical treatment across different counties and the influencing factors from both the inflow and outflow perspectives.Methods Using the fourth quarter data of 2019 from the medical record index,with Sichuan Province as the research area,it analyzed the spatial flow of patients based on the patient's county of residence,the county where the hospital is located,and the number of mobile patients.By combining information at the individual patient level,healthcare institution level,and county level,it established two-level random intercept logistic regression analysis to explore the influencing factors from the perspectives of inflow and outflow.Results The proportion of patients seeking medical treatment across different counties in Sichuan is 22.90%.The majority of patients,with a population of over one thousand,are concentrated in the eastern region.However,the western region has a higher proportion of patients seeking medical treatment across counties.Chengdu and Mianyang are both the largest sources and recipients of patient flows.Being Han Chinese(49%,P＜0.001),male(2%,P＜0.001),Stable income(6%,P＜0.001)and better medical insurance coverage(16%,P＜0.001)at the patient level,as well as better healthcare resources at the institutional level,and higher economic(20%,P＜0.001)and medical levels(5%,P＜0.001)at the district and county level promote patients seeking medical treatment across counties.Conclusion Hospitalized patients in Sichuan Province tend to seek medical treatment from surrounding counties towards the county centers,as well as flowing to Chengdu from various locations.Promoting hierarchical medical treatment and encouraging patients to seek appropriate medical services can be achieved through strengthening patient health education,improving healthcare service levels,and promoting coordinated development between the economy and medical industry.