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Objective:To observe the expression of angiopoietin-like protein 4 (ANGPTL4) signaling pathway in adenine-induced chronic kidney disease (CKD) rat model, and to explore the role of this pathway in renal fibrosis.Methods:Thirty-six male Sprague-Dawley rats were randomly divided into control group (saline, intragastric administration, n=15) and CKD group (250 mg·kg -1·d -1 2.5% adenine, intragastric administration, n=21). At the end of the 1st, 2nd and 4th week, 5 rats were randomly selected from each group. Renal function and 24-hour urinary protein quantity were measured. HE and Masson staining were used to observe the pathological changes of kidneys. Immunohistochemistry and real-time PCR were used to detect renal protein and mRNA expressions of hypoxia-inducible factor-1α (HIF-1α), ANGPTL4, bone morphogenetic protein 7 (BMP7), Smad1, α-smooth muscle actin (α-SMA) and type Ⅰ collagen (Col-Ⅰ). Pearson correlation analysis was used to analyze the correlation between the different indicators. Results:(1) Compared with the control group, the expression levels of serum creatinine and blood urea nitrogen in CKD group were higher at each time point, and the expression levels of 24-hour urinary protein quantity were higher at the end of the 2nd and 4th week (all P < 0.05). (2) HE and Masson staining showed that there were obvious renal structural disorders and collagen fiber deposition at each time point in CKD group compared with the control group, which got worse with time. (3) The results of immunohistochemistry and real-time PCR showed that compared with the control group, the protein and mRNA expression levels of ANGPTL4, α-SMA and Col-Ⅰ were higher, while the protein and mRNA expression levels of BMP7 and Smad1 were lower at the end of the 1st, 2nd and 4th week, and the protein and mRNA expression levels of HIF-1α were higher at the end of 2nd and 4th week in CKD group (all P < 0.05). (4) Correlation analysis results showed that HIF-1α and ANGPTL4 mRNA expression were positively correlated with α-SMA mRNA ( r=0.919, P < 0.001; r=0.757, P < 0.001), and also positively correlated with Col-Ⅰ mRNA ( r=0.925, P < 0.001; r=0.777, P < 0.001). HIF-1α mRNA expression was positively correlated with ANGPTL4 mRNA ( r=0.766, P < 0.001). There were significant negative correlations between HIF-1α, ANGPTL4 mRNA and BMP7 mRNA ( r=-0.652, P < 0.001; r=-0.741, P < 0.001). Conclusions:ANGPTL4 signaling pathway may be activated in adenine-induced CKD rat model, and involved in the renal fibrosis process of CKD.
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Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.
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Objective:To analyze the changes in serum metabolites of patients with uremia using ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS), and provide a theoretical basis for the prevention and treatment of uremia.Methods:Uremia patients from the Department of Nephrology, the Affiliated Hospital of Southwest Medical University, and the volunteers from the Health Examination Center were enrolled in this study. According to the inclusion and exclusion criteria, 20 uremia patients (experimental group) and 20 volunteers (control group) were screened out. UHPLC-MS was used to detect the metabolites in the serum of subjects from the two groups, and difference analysis was made to screen the different metabolites, followed by correlation analysis and pathway enrichment study.Results:A total of 412 metabolites were identified by UHPLC-MS. Principal components analysis (PCA) proved that these metabolites could distinguish the control group and the experimental group well. The criteria [variable importance for the projection (VIP)>1, fold changes (FC)>1.25 or FC<0.8 and P value<0.05] was set to screen those significantly different metabolites. Finally, 28 significantly different metabolites were screened out, of which 18 metabolites increased significantly, the other 10 different metabolites decreased significantly. Correlation analysis results proved a certain correlation among 28 different metabolites and the experimental group and control group samples, and between the 28 differential metabolites themselves. Enrichment analysis found that 28 different metabolites might enrich the catecholamine biosynthetic pathway, and pathway analysis suggested that 28 different metabolites might affect glutamate, aspartame acid and glutamate metabolic pathways. Conclusion:Based on metabonomic analysis, some metabolites in the serum of patients with uremia have changed, which can affect some metabolic pathways, thus affecting the pathophysiological process of patients with uremia.
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Objective To study the effect of moxibustion acupuncture and Chinese medicine external treatment for the severe knee osteoarthritis. Methods A total of 86 severe knee osteoarthritis patients were enrolled between December 2014 and December 2016, in Department of Integrated TCM & Western Medicine, Shijiazhuang first hospital. According to the enrolled sequency, patients were divided into observation group and control group, 43 in each group. The control group was treated with intra-articular injection of sodium hyaluronate of 2ml, and the observation group was treated with the combined acupuncture moxibustion and traditional Chinese medicine external treatment on the basis of the control group. Two groups were performed for 3 months of follow-up. The clinical effect, WOMAC values, VAS score and Lysholm scale, and the serum high sensitivity C reactive protein (hs-CRP), interleukin 1 (IL-1) and tumor necrosis factor a (TNF-a) changes before and after the treatment were observed and compared. Results The total effective rate of observation group was 93.0％ (40/43), while control group total effective rate was 76.7％ (33/43), and the differences between two groups was statistically significant (χ2=4.441, P=0.035). After treatment, the WOMAC joint stiffness scores (3.2 ± 1.2 vs. 4.8 ± 2.1, t=4.338), joint pain (4.2 ± 1.3 vs. 5.9 ± 1.7, t=4.903), daily activities (14.5 ± 2.8 vs. 18.7 ± 2.9, t=6.832) in observation group were significantly lower than those in the control group. The VAS score (2.5 ± 0.8 vs. 4.1 ± 1.2, t=7.275) in observation group was significantly lower than the control group, while the Lysholm score (74.2 ± 3.7 vs. 67.4 ± 3.9, t=8.295) was significantly higher than the control group (P<0.05). The serum hs-CRP (8.34 ± 2.24 mg/L vs. 13.67 ± 2.54 mg/L, t=10.321), IL-1 (0.85 ± 0.11 ng/L vs. 1.32 ± 0.42 ng/L, t=7.099), TNF-a (98.67 ± 15.74 ng/L vs. 178.44 ± 26.53 ng/L, t=16.955) in the observation group patients were significantly lower than those in the control group (P<0.05). Conclusions The acupuncture combined moxibustion and traditional Chinese medicine external treatment could treat severe knee osteoarthritis, improve the function of knee joint.
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Objective To observe the expression of Notch1 signaling pathway in the aorta of chronic kidney disease (CKD) rats with vascular calcification and to explore the role of this signaling pathway activation in aortic calcification of CKD.Methods A total of 40 male SD rats were randomly divided into normal group (Nor group) and CKD with vascular calcification group (CKD+VC group).Rats in each group were sacrificed at 4 weeks,6 weeks and 8 weeks respectively after the success of modeling.Their 24-hour urine was reserved to test 24 hour urine protein (24 h Upro);blood sample was collected from abdominal aorta to test blood urea nitrogen (BUN),serum creatinine (Scr),Ca and P.The histopathology of renal was detected by HE staining.The aortic calcification was detected by alizarin red S staining.Immunohistochemistry (IHC) was used to test the protein expressions of alpha-smooth muscle actin (or-SMA),Runt-related transcription factor 2 (Runx2),Notchl,recombination signal-binding protein for immunoglobulin kappa J region (RBP-Jκ),Msh homeobox 2 (Msx2),Jagged1 and Notch1 intracellular domain (N1-ICD) in the aorta.Real time PCR was applied to detect the mRNA expressions of α-SMA,smooth muscle 22 alpha (SM22α),Runx2,alkaline phosphatase (ALP),Notch1,RBP-Jκ,Msx2 and Jagged1.Results Compared with those in Nor group,24 h Upro,BUN and Scr increased in the CKD+VC group at 4th,6th and 8th weeks (all P ＜ 0.05).Numerous continuous calcified nodules were detected in the vascular wall of the CKD+VC group,but none in Nor group.As compared with Nor group,the expression of α-SMA was low,while the expression of Runx2 was relatively high in the CKD+VC rats at each time point (all P ＜ 0.05).The expressions of Notchl,RBP-Jκ,Msx2,Jaggedl and NI-ICD in the Nor group were slightly appeared in the aortic wall,while in CKD+VC group these signal protein expressions increased relatively during the experimental period (all P ＜ 0.05).As compared with Nor group,the expressions of α-SMA and SM22α mRNA were low,yet the expressions of Runx2 and ALP mRNA were high in the CKD+VC rats at each time point (all P ＜ 0.05).The mRNA levels of Notch1,RBP-Jκ,Msx2 and Jagged1 in the CKD+VC group at each time point were significantly up-regulated as compared with the Nor group (all P ＜ 0.05).Conclusions There exist phenotypic changes in smooth muscle cells and activations of Notch1/RBP-Jκ/Msx2 signaling pathway in CKD rats with vascular calcification.It may be one of the important signal transduction pathways.
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Angioimmunoblastic T-cell lymphoma (AITL) is one of the most common subtypes of peripheral T-cell lymphomas. It is a fol-licular T-helper-derived neoplasm, and characterized by the presence of some genetic alterations, such as mutations in TET2, DN-MT3A, IDH2, and RHOA. Anthracycline-containing regimens represent the most widely adopted first-line option; however, new biolog-ic agents should be designed and incorporated to improve treatment response. The elucidation of the specific roles of these genetic al-terations in AITL will facilitate the development of molecularly targeted therapies to treat this disease.
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Objective To compare the differences in cognitive function and behavioral and psychological symptoms between patients with Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD). Methods Thirty-six AD patients and 20 bvFTD patients at mild-to-moderate stage, who were biomarker-confirmed by positron emission tomography (PET), were assessed with a neuropsychological battery and neuropsychiatry inventory (NPI). Cognitive domains, including memory, language, information processing speed and executive function, and behavioral and psychological symptoms were assessed and compared. Results AD patients had lower scores in immediate recall, delayed recall and recognition than bvFTD patients (all P<0.05); while bvFTD patients had poorer performance in language and executive function than AD patients (all P<0.05). The NPI total score was significantly higher in patients with bvFTD compared with patients with AD (17.5±5.7 vs 9.3±3.5, P<0.05). In respect to the 12 items of NPI, the incidence of agitation and irritability was higher in AD group than in bvFTD group (72.2%vs 35.0%, 55.6%vs 20.0%, all P<0.05);while the incidence of apathy, disinhibition, euphoria, aberrant motor behavior and appetite/eating was higher in bvFTD group than in AD group (65.0%vs 33.3%, 80.0% vs 5.5%, 70.0% vs 5.6%, 40.0% vs 11.1%, 50.0% vs 5.6%, all P<0.05). Conclusion Comprehensive neuropsychological assessment and evaluation of behavioral and psychological symptoms of patients with dementia are helpful in distinguishing AD from bvFTD.
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Objective To investigate the effect of education in pregnant women’s school on primipara mode of delivery and puerperal behavior.Methods Two hundred and twenty cases who delivered in our hospital and paid postpartum visits were divided into observation group and control group equally according to whether they had attended the pregnant women’s school.The observation group included those having attended the school and the control those who had not.The two groups were compared in terms of primipara mode of delivery and puerperal behavior.Results The rates of maternal vaginal delivery and cesarean section rate in observation group were 71.8%and 28.2%,both significantly higher than those of the control group(52.7%and 47.3%)(P<0.01).The rate of caesarean section due to social factors in the observation group was significantly lower than that of the control group(P<0.05).Besides,the observation group had higher rates of puerperiumal shampoo, showering, eating vegetables and fruits,brushing,use of air-conditioners than the control group did(all P<0.01).Conclusions Prenatal maternal health education in the pregnant women’s school affects puerperous behavior.It suggests that prenatal parturients actively participate in related education on maternal health care,which can help establish a good pregnancy and puerperium maternal behavior,reduce maternal cesarean section and thus help them live through puerperium.
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Objective To study the effect of community health education on lactation mastitis and breast feeding.Method Ninety parturients were given community health education for 6 months and then the rates of mastitis and breast feeding were recorded.Results The mastitis morbidity was 3.3%and the rate of breast feeding was 97.8%.Conclusion The implementation of the community health education can reduce the morbidity of maternal mastitis and raise the rate of breast feeding.
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Objective To observe the expression of HER-2 and TOPO-Ⅱα in ovarian epithelial cancer,analyze the correlation between their expression and provide theoretical basis for clinical diagnosis,prognosis and treatment. Methods Expression levels of HER-2 and TOPO- Ⅱα in 10 normal ovarian tissues,20 benign tumors and 58 cases of ovarian epithelial cancers were detected by immunohistochemical method, and their correlations with pathological features were analyzed. Results The positive expression rate of HER-2 in normal ovarian and benign tumor tissues were significantly lower than ovarian epithelial cancers respectively ( 10. 0% , 15.0% VS 46. 6% ;P ＜ 0. 05 ). The positive expression rate of TOPO- Ⅱα in ovarian epithelial cancers was significantly higher than normal and benign epithelial ovarian tumor tissue (53.4% vs 10. 0%, and 15.0%,Ps ＜ 0. 05 ), but we did not find significant difference in the comparison between normal and benign epithelial ovarian tumor tissue ( Ps ＞ 0. 05 ). The expression of HER-2 and TOPO- Ⅱα were significantly correlated with clinical stages, histological differentiation of tumor cells (Ps ＜ 0. 05 ) ,but there were no correlations between the age or histological type. In ovarian cancer tissues, a positive correlation between the expression of HER-2 and TOPO- Ⅱα was observed ( r = 0. 324, P ＜ 0. 05 ) . Conclusion The overexpression of HER-2 and TOPO- Ⅱαplay an important role in ovarian carcinogenesis and development. The expression of HER-2 is positively correlated with TOPO- Ⅱα in ovarian epithelial cancers. Coexpression of the two moleculars may be involved in the development and progression of ovarian epithelial cancer, which should be further studied.
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Objective To study the clinical significance ofneutrophil gelatinase-associated lipocalin (NGAL), which in serial plasma and urine samples was measured in participants with lupus nephritis (LN)and healthy persons. Methods NGAL in serial plasma and urine samples was measured by enzyme-linked immunosorbent assay (EL.ISA) in 35 patients with LN by 1997 ACR systemic lupus erythematosus (SLE)standard with varied degree of kidney damage and 30 healthy persons with matching sex and age in physical examination center. Disease activity was measured by the SLE disease activity index (SLEDAI-2K),and 35LN patients were classified in active group and (25 cases) non-active group (10 cases) according to the SLEDAI-2K. Results Urinary NGAL were significantly increased in LN patients [(78.94 ± 81.97) μg/L]compared with healthy persons[(28.50 ± 18.08) μ g/L] (P = 0.002). And urinary NGAL were significantly increased in active group [(92.90 ± 94.88) μg/L] compared with non-active group [(48.20 ± 24.77)μ g/L] (P = 0.049). NGAL in serial plasma had no statistically significant difference between active group and non-active group (P ＞0.05). Conclusions NGAL in urine but not in plasma represents a novel biomarker for renal disease activity in LN. The increase might be related to renal tubule pathological changes.
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Objective To investigate the influence of early rehabilitation and defibrase on the hemodynamic cerebral vascular dynamic index (CVDI) of hemiplegic patients with acute cerebral infarction. Methods Ninety hemiplegic patients with acute infarction were randomly divided into a rehabilitation and a control group. Both groups received defibrase routine treatment. The rehabilitation group received systematic rehabilitation training in addition. The Fugl-Meyer assessment ( FMA) , the Scandinavian Scoring Scale ( SSS) and Barthel's index ( MBI) were employed to evaluate the functioning of the two groups. The CVDIs of all patients were quantified before and after treatment. Results The FMA, MBI and SSS scores as well as the CVDIs of both groups had improved after 4 weeks of treatment, but all were more improved in the rehabilitation group than in the control group. Conclusions Early rehabilitation was effective for relieving neurological impairment and improving ability in the activities of daily living for patients with acute cerebral infarction.
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AIM: To investigate the effect of Qingrehuayuziyin Fang on lymphocyte apoptosis and expression of Fas and FasL in peripheral blood in the patients with systemic lupus erythematosus(SLE).METHODS: Eighty patients with SLE were selected and divided randomly into two groups,40 in the therapy group and 40 in control group respectively.Patients were get the treatment of Qingrehuayuziyin Fang combined hormone(prednisone) as therapy group and get hormone treating only as control group.After treating three months,lymphocyte were collected to be detected the rate of apoptosis by flow cytometer.Meanwhile,the expression of Fas and FasL were analyzed by RT-PCR.RESULTS: After three months treating,the rate of lymphocyte apoptosis was decreased significantly in therapy group compared with that in control group(P
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OBJECTIVE： To observe the therapeutic effects of 0.3％ levofloxacin eyedrops on the acute bacterial conjunctivitis and keratitis.METHODS： The patients were randomly divided into treated group and control group.They were given 0.3％ levofloxacin and 0.3％ ofloxacin eyedrops respectively.The effects were compared between two groups.RESULTS： From April 1998 to December 1998， 132 cases were enrolled in the study： treated group 67 cases， control group 65 cases.The positive rates of bacterial culture were over 80％ in both groups.It showed that there was no significant difference between two eyedrops in the curative and effective rates， but the mean cure day of keratitis in levofloxacin group was significantly shorter than that in ofloxacin group.CONCLUSION： Levofloxacin eyedrops is effective and safe in treating bacterial conjunctivitis and keratitis， and the therapeutic course is short and no obvious ARDs occur.
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To study action mechanism and time of administration of indomethacin in SMAO shock rabbits. Method:Thirty-two SMAO shock rabbits were randomly divided into four groups: control group A,indomethacin 5mg/kg I.V. at the occlusion of superior mesenteric artery (group B), indomethacin 5mg/kg L V. immediately after clamp being removed(group C) and the same dose 30min after clamp being removed(group D). Survival rate,hemodynamics, plasma calcium, myocardial calcium, TXB_2 and 6-keto-PGF_1. levels were observed in 4h shock period. Myocardial apecmen were examined with electronic microscope. Result: After indomethacin I.V,the survival rate was higher and bemodynamie better than those of controll. The plasma calcium level remained stable in indomethacin groups. Myocardial calcium content of group B and C was lower than that of group D and A. The TXB_2 and 6-ketoPGF_1. contents were similar in all groups. Under electronic microscope, the damages were slightest in group C and most serious in group D and A among the four groups. Conclusion:Indomethacin has a beneficial effect on the SMAO shock rabbits ,the mechanism of which can be related to improving myocardium contractivity as well as to blocking calcium channel,rather than the action through prostaglandins. The time of administration should be early as possible after shock.