1.The efficacy and safety of low-dose rituximab in treatment of primary Sj(..o)gren's syndrome with thrombocytopenia
Li ZHOU ; Xiafei XIN ; Huaxiang WU
Chinese Journal of Internal Medicine 2012;51(1):37-41
Objective To investigate the clinical efficacy and safety of low-dose rituximab (RTX) for patients in primary Sj(..o)gren's syndrome (pSS) with thrombocytopenia.Methods Four pSS patients,2 with refractory thrombocytopenia and 2 with glucocorticoid-dependent thrombocytopenia,were treated with rituximab at 100 mg,intravenous,weekly for a total of two cycles,together with prednisone 1-2 mg · kg-1 ·d-1,and the counts of platelets and B-cells were evaluated.Results Efficacy of treatment was observed in all patients.The counts of platelets,at (3-39) x 109/L baseline,incleased in 1-2 weeks,and went up to ( 107-241 ) × 109/L in 3-8 weeks.Sustained remission had been achieved for 27-52 weeks.The doses of prednisone were tappered to 3.75-7.50 mg/day in 12 weeks.One patient who relapsed at the 27th week (platelet count 47 x 109/L),was retreated with 100 mg of RTX and still had good efficacy.The counts of B-cells reduced to (0.007-0.010) × 109/L,but they did not achieved the depletion.There were no severe adverse events during RTX therapy.Conclusions Our study has shown good efficacy and tolerability of lowdose RTX for pSS with thrombocytopenia.Low-dose RTX allows for reduction in corticosteroid doses and B-cells,while large-scale randomized double-blind controlled trials are needed to confirm the results.
2.Relationship between free radicals and microvascular complications in elderly patients with type 2 diabetes mellitus
Huaxiang WU ; Zuogui SONG ; Junfu ZHOU
Chinese Journal of Geriatrics 2000;0(04):-
Objective To investigate the plasma level of free radicals and antioxidative activity in elderly patients with type 2 diabetes mellitus and relation to microvascular complication. Methods The concentration of erythrocyte lipoperoxides(LPO), plasma vitamin E(VE), plasma vitamin C(VC), plasma betacarotene(? CAR), whole blood glutathione(GSH) and the activity of erythrocyte superoxide dismutase(SOD), erythrocyte catalase (CAT), erythrocyte glutathione peroxidase(GSH PX) in 65 elderly patients with type 2 diabetes and 65 healthy patients were measured. Meanwhile, fasting glucose, 2 hours post meal glucose, glycated hemoglobin, fasting and post meal C peptide, triglycerides, cholesterol, urine albumin excretion rate, electromyogram were measured. Results Compared with the healthy patients, the average value of LPO(42 97?6 99)nmol/g and (31 59?7 44)nmol/g, VC (40 98?10 51)?mol/L and (52 23?10 51)?mol/L, VE (16 44?2 45)?mol/L and (23 04?5 38)?mol/L, ? CAR (1 19?0 23)?mol/L and (1 63?0 40)?mol/L and GSH(0 98?0 16 vs 1 25?0 20) in elderly patients with type 2 diabetes were significantly increased, while the activities of SOD(1712 44?157 04)U/L and (1 928 38?143 44)U/L, CAT(217 01?29 36)?g/g vs (264 40?63 55)?g/g, GSH PX(21 01?3 38)?10 -10 U/RBC vs (25 16?6 41)?10 -10 U/RBC were obviously decreased. The change was more obvious in the patients with microvascular complication compared with those without microvascular complication. Plasma level of LPO were correlated positively with age(r=0 310, P
3.The effect of different inItension electrotherapy to rabbits' FERG
Yuezhu ZHAO ; Wenzhou LIU ; Huaxiang ZHOU ; Junguo DUAN
Chinese Journal of Primary Medicine and Pharmacy 2008;15(3):386-387,后插2
Objective To discuss the effect of different intension electrotherapy to rabbits'FERG,Methods Using the FERG as the target,to stimulate the TAIXI point with 0.2,0.8,2.0 and 4.0mA inrension eleetrotherapy,then observe the change of the rabbits'FERG during and after the stimulation.Results 0.8mA intension can lead to the delay of the FERG a-wave's latency obviously.The lower or higher.stimulation has little effect to the awave's latency.All kinds of stimulation to the b-wave's latency has little difference,but the effect to the amplitude has significant difference.While the stimulating intension below 2mA in 15 minutes,the b-wave's amplitude rise obviously with the intension's rising,but the amplitude will fall when the intension get to 4mA.Conclusion The effect of electrotherapy on the retina'function has osculation relationship with the electrotherapy intenmon,the best effect needs the most fitful intension of stimulation.
4.Clinical analysis of bronchopulmonary amyloidosis secondary to primary Sj(O)gren's syndrome
Li ZHOU ; Xiafei XIN ; Huaxiang WU ; Jing XUE
Chinese Journal of Rheumatology 2012;16(6):398-401,后插1
Objective To investigate the clinical characteristics of bronchopulmonary amyloidosis secondmy to primary Sj(0)gren's syndrome (pSS).Methods One patient in our series and 42 patients in the literatures were analyzed.The clinical manifestations,imaging features,diagnosis,treatments and prognosis of these patients were described respectively.Results Among the 43 cases,42 patients were female (98%).The median age was 57 (range 29-79) years.The diagnosis of bronchopulmonary amyloidosis was made subsequently to that of pSS with a median delay of 8.9 (range 0-30) years.Thirty-eight cases (88%) were localized amyloidosis.Most cases were related to AL amyloidosis (21/28,75% ).The main clinical manifestations included cough (18/38,47%),short of breath (13/38,34% ),sputum (9/38,24%) and hemoptysis (5/38,13% ).Nine patients (9/38,24% ) had no clinical symptoms.The most common patterns of radiological manifestations included multiple nodules (40/43,93%),multiple cysts or bullae (16/43,37%),interstitial lung disease (16/43,37% ),irregular luminal narrowing and airway wall thickening (8/43,19% ).The pulmonary function test was done in 17 patients,which revealed moderate to severe reduced diffusion capacity for carbon monoxide (8/17,47% ).The diagnosis of amyloidosis was made based on pathological findings in all cases.Pathologic examination showed diffuse deposits of amorphous,eosinophilic,Congo-red positive staining material.The treatments were symptomatic.The prognosis of most patients was good.The median follow-up time was 26.5 (range 2-96) months,only 2 patients died during the follow-up.Conclusion The bronchopulmonary amyloidosis secondary to pSS is localized amyloidosis in most cases.Clinical manifestations depend on the location and extent of airway lesions.The appearance of multiple lung nodules with calcified or cysts in chest images should be considered as secondary amyloidosis.No specific therapy is available for these cases,however,this condition in majority of patients progresses slowly.
5.The expression of Semaphorin 5A in patients with rheumatoid arthritis and its effect on osteoclastogenesis
Yan DU ; Jiawei WANG ; Meiju ZHOU ; Xinyu WU ; Jing XUE ; Huaxiang WU
Chinese Journal of Internal Medicine 2018;57(9):661-666
Objective To investigate the clinical significance of soluble Semaphorin 5A(Sema 5A) in patients of rheumatoid arthritis(RA) and the effect of Sema 5A on osteoclastogenesis in RAW264.7 cells.Methods (1)Soluble Sema 5A was detected in the serum of 62 RA patients,30 osteoarthritis(OA) patients and 48 healthy controls(HC) by enzyme-linked immunosorbent assay(ELISA).The relationships between serum Sema 5A and disease activity,radiographic severity and laboratory parameters were investigated in RA patients.(2)RAW264.7 cells were treated with different concentrations of Sema 5A(0,0.5,1,2.5,5 μg/ml).After 7 days,tartrate-resistant acid phosphate(TRAP) staining was performed.The mRNA levels of TRAP,cathepsin-K and matrix metallopeptidase 9(MMP-9) were tested using real-time polymerase chain reaction (RT-PCR).(3)Bone resorption area of dentine slides cultured with RAW264.7 cells was calculated after Sema 5A (5μg/ml) treatment.Results (1)The serum Sema 5A in RA patients[(5.24±0.59)μg/L] was significantly higher than those in healthy controls[(2.93±0.34)μg/L,P<0.01] and OA patients[(2.68±0.47)μg/L,P<0.05].The Sema 5A level in RA patients was positively correlated with disease activity score with 28 joint using C-reactive protein(DAS28-CRP),clinical disease activity index (CDAI),C-reactive protein(CRP) and sharp scores(P<0.05 or P<0.01).In addition,the serum Sema 5A in RA patients with positive anti-cyclic citrullinated peptide(CCP) antibody was significantly greater than that of anti-CCP antibody-negative patients (P<0.05).(2)After RAW264.7 cells were treated with Sema 5A,the number of TRAP positive osteoclasts increased according to the increase of Sema 5A concentration with maximal effect at 5 μg/ml.Meanwhile,Sema 5A promoted mRNA expression of TRAP,Cathepsin-K and MMP-9.(3)Bone resorption area increased when RAW264.7 cells were treated with Sema 5A(5 μg/ml).Conclusions Serum Sema 5A is elevated in RA patients and correlated with disease activity and radiographic severity.Sema 5A promotes osteoclastogenesis of RAW264.7 cells.
6.Prenatal diagnosis of a novel SOX10 mutation in a patient with syndromic hearing loss.
Chiyan ZHOU ; Xiaodan LIU ; Qinhao SONG ; Suping LI ; Shaoping ZHONG ; Huaxiang SHEN
Chinese Journal of Medical Genetics 2019;36(5):477-479
OBJECTIVE:
To explore the genetic basis for a patient with syndromic hearing loss.
METHODS:
Genomic DNA of the patient was extracted, for which 127 deafness-related genes were enriched with a chip. Following next generation sequencing, pathogenic loci in exonic regions were analyzed through comparison against the databases. Genotype of her fetus for the suspected site was determined by testing the amniotic fluid sample. qPCR method was applied to verify the deletion of a large fragment.
RESULTS:
The proband was diagnosed with Waardenburg syndrome type 2, and had harbored a novel heterozygous deletion of the exons 3 and 4 of the SOX10 gene. Her fetus was found to carry the same deletion and presented with blue eyes and deafness after birth.
CONCLUSION
Waardenburg syndrome type 2 due to SOX10 gene deletion may feature autosomal dominant inheritance with incomplete penetrance. The deletion of exons 3 and 4 of the SOX10 gene probably underlies the disease in this family.
Eye Color
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Female
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Hearing Loss
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Humans
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Mutation
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Pedigree
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Pregnancy
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Prenatal Diagnosis
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SOXE Transcription Factors
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genetics
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Waardenburg Syndrome
7.Experimentation of effect of PD-1 inhibitor on myocardial inflammation microenvironment and radiation-induced injury
Kaiyan ZHOU ; Lingfeng LIU ; Li CAO ; Gang WANG ; Chaofen ZHAO ; Huaxiang KUANG ; Yinxiang HU ; Haojia ZHANG ; Shengfa SU ; Bing LU
Chinese Journal of Radiation Oncology 2022;31(1):79-84
Objective:To explore the potential mechanism of PD-1 inhibitor P on RIMI from the perspective of immune microenvironment.Methods:To establish a mouse model of radiation-induced myocardial injury (RIMI), twenty C57BL/6 mice were randomly divided into 4 groups, 5 in each group. Group A was the healthy control group; Group B was the PD-1 inhibitor group; Group C was the simple irradiation group, with a heart irradiation of 15 Gy; Group D was the irradiation+ PD-1 inhibitor group. One month after irradiation, the mice were anesthetized and sacrificed. The morphological changes of myocardial tissues were observed by HE staining. The myocardial fibrosis was assessed by Masson staining. CD 3+ , CD 3+ CD 4+ , CD 3+ CD 8 lymphocyte subsets and cytokines (IL-4, IL-6, IL-17A, TNF-α, TGF-β 1 and INF-γ) levels were determined by flow cytometry. The apoptosis rate of myocardial cells was detected by TUNE. Results:One month after irradiation, there was no obvious myocardial fibrosis in group B, and collagen fibers were distributed in the interstitium of myocardial cells in groups C and D. Semi-quantitative analysis results showed that the myocardial collagen volume fraction (CVF) of groups A, B, C and D were (1.97±0.36)%, (2.83±1.03)%, (5.39±0.77)% and (7.72±1.43)%, respectively. The CVF between group A and group B was similar ( P=0.314), and the differences in CVF between the other groups were statistically significant (all P<0.05). Compared with group A, the absolute value and percentage of CD 3+ T lymphocytes were significantly increased in groups B, C and D (all P<0.01). The values in group D were significantly higher than those in group B and group C (all P<0.01); The absolute value and percentage of CD 3+ CD4 T lymphocytes were similar among four groups (all P>0.05); The absolute value and percentage of CD 3+ CD 8 T lymphocytes in group D were significantly higher than those in groups A, B and C (all P<0.001). The expression levels of IL-6, IL-17A, and TGF-β 1 in group D were significantly higher compared with those in groups A, B and C (all P<0.001). The apoptotic index was gradually increased in four groups, and the differences in apoptotic index among four groups were statistically significant (all P<0.001). Conclusion:PD-1 inhibitors can aggravate RIMI by promoting myocardial immune inflammatory response.
8.Sodium cyanide exacerbates hypoxia induced brain nerve damage in mice and its mechanism
Pengfei LI ; Huaxiang SHI ; Mengwei ZHOU ; Jiabin GUO ; Yongan WANG ; Liyun WANG
Chinese Journal of Pharmacology and Toxicology 2024;38(2):89-96
OBJECTIVE To investigate the effect and mechanism of acute exposure to sodium cyanide(NaCN)on brain nerve damage induced by closed hypoxia in mice.METHODS ① Mice were randomly divided into hypoxia+NaCN 0(hypoxia control group),2.56,3.8,and 5.1 mg·kg-1 groups.After ip adminis-tration of different concentrations of NaCN,the mice were immediately placed into a closed hypoxic tank and the hypoxia survival time was observed.②Mice were divided into normal control,NaCN 3.8 mg·kg-1,hypoxia(30 and 60 min)and NaCN 3.8 mg·kg-1+hypoxia(30 and 60 min)groups.After grouping,the pH,oxygen saturation(sO2),oxygen tension(pO2)and carbon dioxide partial pressure(pCO2)of arterial blood of mice were detected using an arterial blood gas analyzer.The cortical cerebral blood flow of mice was detected using a laser speckle imager.The dry and wet brain tissue were weighed separately,and the brain moisture content was calculated.The kit was used to detect the activity of total superoxide dismutase(T-SOD)and the content of malondialdehyde(MDA)in the hippocampus.TUNEL staining was used to detect the apoptosis rate of cells in the hippocampus.HE staining was used to detect path-ological changes in the hippocampus.RESULTS ①Compared with the hypoxic control group,the sur-vival time of mice in the hypoxic+NaCN groups was significantly prolonged(P<0.01).②Compared with the normal control group,the hypoxia 30 min group showed upregulation of arterial blood p CO2(P<0.05),downregulation of p O2(P<0.05).The hypoxia 60 min group showed upregulation of arterial blood p CO2(P<0.05)and downregulation of cortical cerebral blood flow(P<0.05).In the NaCN 3.8 mg·kg-1 group,arterial blood p O2 and s O2 were significantly downregulated(P<0.05),so was cortical cerebral blood flow(P<0.01),but MDA content and T-SOD activity were significantly upregulated(P<0.01),and the brain moisture content was increased(P<0.01).Compared with the hypoxia 30 min group,s O2 and p O2 of arterial blood in the NaCN+hypoxia 30 min group were significantly upregulated(P<0.05),while p CO2 was significantly downregulated(P<0.05).Compared with the hypoxia group at corresponding time points,the NaCN+hypoxia 30 or 60 min groups showed significant downregulation of cerebral blood flow(P<0.01),significant upregulation of MDA content and T-SOD activity(P<0.01),and signifi-cant upregulation of brain moisture content(P<0.01).HE staining results showed that the NaCN 3.8 mg·kg-1 group and the NaCN+hypoxia group(30 or 60 min)showed significant cell swelling and vacuolization in cells in the hippocampal tissue,a decrease in the number of neurons,nuclear pyknosis and deep staining.TUNEL fluorescence results showed that the NaCN 3.8 mg·kg-1 group significantly increased the apop-tosis rate of the mouse hippocampus compared with the normal control group(P<0.05).The NaCN+ hypoxia 30 and 60 min groups significantly increased the apoptosis rate of the mouse hippocampus compared with the hypoxia group at corresponding time points(P<0.05).CONCLUSION NaCN can exacerbate hypoxia induced decrease in cerebral blood flow,oxidative stress in brain tissue,and neuro-nal apoptosis in mice,thereby reducing oxygen consumption in closed hypoxic tanks and prolonging their survival time.The mechanism is related to reduced utility of cell oxygen,delaying CO2 accumulation and increasing free oxygen in vivo.
9.Expression of leukocyte immunoglobulin-like receptor A3 in CD14 monocytes of patients with rheumatoid arthritis.
Meiju ZHOU ; Jiawei WANG ; Wenjia SUN ; Xinyu WU ; Jing XUE ; Huaxiang WU ; Yan DU
Journal of Zhejiang University. Medical sciences 2018;47(4):395-399
OBJECTIVE:
To investigate the expression of leukocyte immunoglobulin-like receptor A3 (LILRA3) in CD14 monocytes of patients with rheumatoid arthritis (RA).
METHODS:
Fifty three RA patients admitted in the Second Affiliated Hospital of Zhejiang University School of Medicine from February 2017 to August 2017, and 21 healthy subjects were enrolled in the study. The expression of LILRA3 in CD14 monocyte subset was determined by flow cytometry, and its correlations with clinical features, laboratory examination results, antibodies and disease activity were analyzed.
RESULTS:
LILRA3 percentage in the CD14 monocyte subset of RA patients was higher than that in the healthy controls (<0.01). The percentage of LILRA3 was positively correlated with number of tenderness joints, number of swollen joints and erythrocyte sedimentation rate (=0.280, 0.371, 0.341, <0.05 or <0.01), but was not correlated with the age, course of disease, Sharp score, C reactive protein, blood routine index and immunoglobulin (all >0.05). In addition, the percentages of LILRA3 in the monocytes of rheumatoid factor (RF)-positive or anti-cyclic citrullinated peptide (CCP) antibody-positive patients were significantly higher than those of the RF-or anti-CCP antibody-negative patients (all < 0.05); and the percentage of LILRA3 in patients with DAS28>5.1 was higher than that in patients with DAS28 ≤ 5.1 (<0.05).
CONCLUSIONS
The expression of LILRA3 is up-regulated in CD14 monocyte subset isolated from RA patients, and it is correlated with disease activity.
Arthritis, Rheumatoid
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blood
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physiopathology
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Autoantibodies
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blood
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Biomarkers
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blood
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Flow Cytometry
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Humans
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Monocytes
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metabolism
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Receptors, Immunologic
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genetics
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Up-Regulation