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Objective To evaluate the clinical characteristics and prognostic predictors of patients with diffuse alveolar hemorrhage (DAH) and/or interstitial lung disease (ILD) secondary to microscopic polyangiitis (MPA) in a Chinese general hospital. Methods We retrospectively reviewed the medical records of MPA patients admitted to internal medicine departments between the year 2002 and 2012. The patients were divided into the ILD, DAH, DAH combined with ILD (DAHILD), and no pulmonary involvement (NPI) groups according to pulmonary involvement patterns. The clinical characteristics at diagnosis were analyzed. The risk factors associated with short-term death and long-term death were identified with Logistic regression and Cox analysis.Results Of 193 newly diagnosed MPA patients, 181 patients were enrolled in the research, of which 19 had DAH alone, 96 had ILD alone, 18 had DAH and DAH concurrently, and 48 had NPI. The median of serum creatine level in the DAH group was 449 μmol/L, significantly higher than that in the ILD group (123 μmol/L, Nemenyi = -35.215, P = 0.045) and DAHILD group (359 μmol/L, Nemenyi = -43.609, P = 0.007). The median follow-up time was 67 (range: 1-199) months. Patients in the ILD group were older than those in the DAH group (median: 69 years vs. 57 years, Nemenyi = 43.853, P= 0.005). The patients with both DAH and ILD had combined features of the two subtypes, and the highest mortality (72.2% at the end of follow-up). The elevated white blood cell count was a risk factor for short-term death (OR = 1.103, 95%CI: 1.008-1.207, P = 0.032 for one month; OR = 1.103, 95%CI: 1.026-1.186, P = 0.008 for one year). Old age (HR= 1.044, 95%CI: 1.023-1.066, P < 0.001), cardiovascular system involvement (HR = 2.093, 95%CI: 1.195-3.665, P = 0.010), poor renal function (HR = 1.001, 95%CI: 1.000-1.002, P = 0.032) were risk factors for long-term death. Pulmonary infections (38/54) were the leading causes of death, especially for the patients with ILD. Besides, 49 patients suffered from pulmonary infections in the first year after diagnosis. Conclusions MPA patients who presented with different pulmonary involvement patterns have completely different clinical features. These subtypes probably have different pathogenesis and should be studied separately.
Subject(s)
Humans , Microscopic Polyangiitis/diagnosis , Retrospective Studies , Lung Diseases, Interstitial/complications , Hemorrhage/complications , PrognosisABSTRACT
OBJECTIVE@#To explore the effect of Tangshen Formula (, TSF), a Chinese herbal medicine, on interstitial cells of Cajal (ICC) in the colon of diabetic rats.@*METHODS@#Fifty-four male Wistar rats were randomly divided into normal control (NC, n=14) and high-fat diet (HFD) groups (n=40). After 6 weeks, the rats in the HFD group were injected intraperitoneally streptozotocin once (30 mg/kg). Thirty rats with fasting blood glucose higher than 11.7 mmol/L were randomly divided into diabetes (DM) and TSF groups, 15 rats in each group. Rats in the NC and DM groups were intragastrically administered with saline, and those in the TSF group were given with TSF (2.4 g/kg) once daily for 20 weeks. Expression levels of Bax, Bcl-2, and caspase-3 in colonic smooth muscle layer were measured by Western blotting and immunohistochemical staining. The number of ICC was determined by immunohistochemical staining. Immunofluorescence was used for analyzing the ratio of classically activated macrophages (M1) and alternatively activated macrophages (M2) to total macrophages. Electron microscopy was used to observe the epithelial ultrastructure and junctions.@*RESULTS@#TSF appeared to partially prevented loss of ICC in DM rats (P<0.05). Compared with the NC group, expression levels of Bcl-2, Bax, caspase-3, and TNF-α as well as the ratio of M1 to total macrophages increased in DM rats (all P<0.05), and the ratio of M2 to total macrophages decreased (P<0.05 or P<0.01). Compared with the DM group, TSF decreased the expression levels of abovementioned proteins and restore M2 to total macrophages ratio (P<0.05 or P<0.01). TSF appeared to attenuate the ultrastructural changes of epithelia and improve the tight and desmosome junctions between epithelia reduced in the DM rats.@*CONCLUSION@#Reduced number of ICC in DM rats may be associated with damage of the intestinal barrier. The protective effects of TSF on ICC may be through repair of the epithelial junctions, which attenuates inflammation and inflammation-initiated apoptosis in colon of DM rats.
Subject(s)
Animals , Male , Rats , Colon , Diabetes Mellitus, Experimental/drug therapy , Drugs, Chinese Herbal/therapeutic use , Interstitial Cells of Cajal , Rats, WistarABSTRACT
Lipin1, a member of the lipin family, serves as a phospholipid phosphatase or a co-transcriptional regulator in lipid metabolism. Recent studies also show that lipin1 is involved in many other cellular metabolism processes. However, the clear regulatory mechanism for lipin1 is unknown. The 293T human renal epithelial cell line represents a commonly used and well established expression system for recombinant proteins. Herein, we used two-dimensional polyacrylamide gel electrophoresis (2D-GE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) to explore the changes in protein expression induced by lipin1 overexpression in 293T cells. Western blotting was used to confirm one of the expression changes of related proteins. Subsequently, the function and relationship of these proteins were analyzed by bioinformatics approach. By using 2D-PAGE, approximately 152 proteins were separated and eleven proteins were found to be significantly affected by lipin1 overexpression compared to the control. Among them, three proteins (eEF-1B γ, CCT1 and CCT3) were up-regulated and other eight proteins (NDKA, Stathmin, HNRNP A1, TK, KRT1, PKM, RanBP1 and LDHB) were down-regulated. These proteins were successfully identified with peptide mass fingerprinting using MALDI-TOF-MS after in-gel trypsin digestion. The bioinformatic analysis showed that these proteins are classified into seven protein species, including transferase, cleavage enzyme, cytoskeleton protein, chaperone protein, regulatory protein, structural protein and oxidoreductase. The results highlight the potential roles of lipin1 involved in many cellular metabolism processes, including myelin synthesis, extracellular domain formation, membrane bound vesicle synthesis and companion protein T complex synthesis.
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With the development of molecular pathology,many types of epidermal growth factor receptor (EGFR) mutations have been identified.The efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) patients with different types of EGFR mutations,especially in patients with single rare mutations or complex mutations (co-occurrence of two or more different mutations),has not been fully understood.This study aimed to examine the efficacy of EGFR-TKIs in NSCLC patients with different types of EGFR mutations.Clinical data of 809 NSCLC patients who harbored different types of EGFR mutations and treated from January 2012 to October 2016 at Renmin Hospital and Zhongnan Hospital,Wuhan,were retrospectively reviewed.The clinical characteristics of these patients and the efficacy of EGFR-TKIs were analyzed.Among these patients,377 patients had only the EGFR del-19 mutation,362 patients the EGFR L858R mutation in exon 21,33 patients single rare mutations and 37 patients complex mutations.Among these 809 patients,239 patients were treated with EGFR-TKIs.In all the 239 patients,the disease control rate (DCR) was 93.7％ with two patients (0.2％) achieving complete response (CR),the median progression free survival (PFS) was 13.0 months (95％ confidence interval [CI],11.6-14.4 months),and the median overall survival (OS) was 55.0 months (95％ CI,26.3-83.7 months).Subgroup analysis revealed that the DCR in patients harboring single rare or complex mutations of EGFR was significantly lower than in those with del-19 or L858R mutation (P＜0.001).Patients with classic mutations (del-19 and/or L858R mutations) demonstrated longer PFS (P＜0.001) and OS (P=0.017) than those with uncommon mutations (single rare and/or complex mutations).Furthermore,the patients with single rare mutations had shorter median OS than in those with other mutations.Multivariate Cox regression analysis identified that the type of EGFR mutations was an independent risk factor for PFS (hazard ratio [HR]=0.308,95％ CI,0.191-0.494,P＜0.001) and OS (HR=0.221,95％ CI,0.101-0.480,P＜0.001).The results suggest that the single rare or complex EGFR mutations confer inferior efficacy of EGFR-TKIs treatment to the classic mutations.The prognosis of the single rare EGFR mutations is depressing.EGFR-TKIs may be not a good choice for NSCLC patients with single rare mutations of EGFR.Further studies in these patients with uncommon mutations (especially for the patients with single rare mutations) are needed to determine a better precision treatment.
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BACKGROUND:Total knee arthroplasty is always associated with peripheral blood loss.Blood transfusion not only involves additional cost and prolongs rehabilitation time,but also carries substantial risk of immunologic reaction and disease transmission.Therefore it is very important to reduce blood loss of total knee arthroplasty.OBJECTIVE:To investigate the efficacy and safety of tranexamic acid on reducing blood loss after total knee arthroplasty.METHODS:We enroled 64 patients with primary osteoarthritis undergoing a unilateral total knee arthroplasty and randomized them into two groups,with 32 patients in each group.Tranexamic acid group: patients received intravenous drop infusion of tranexamic acid dissolved in 250 mL normal saline (10 mg/kg) at 15 minutes before operation; control group: patients just received 250 mL normal saline.Intraoperative blood loss,postoperative blood loss,postoperative hemoglobin levels,amount of blood transfusion,and number of patients requiring blood transfusion were compared.Fibrinogen,prothrombin time and other coagulation indicators were also examined before operation and 3 hours after operation.Deep vein thrombosis in both limbs of al patients was examined bythe color Doppler ultrasonography 30 days after operation.RESULTS AND CONCLUSION:There was no significant difference in intraoperative blood loss between the two groups (P＞0.05).Postoperative volume of blood loss was lower in the tranexamic acid group than in the control group (P＜0.001).The amount of blood transfusion and number of patients requiring blood transfusion were lower in the tranexamic acid group than in the control group (P＜0.001).The postoperative hemoglobin levels were obviously higher in the tranexamic acid group than in the control group (P＜0.001).There was no significant difference in coagulation indicators between two groups at postoperative 3 hours,but D-dimer value in the two groups was significantly higher than that before surgery,and the tranexamic acid group was lower than the control group (P＜0.001).No cases appeared deep vein thrombosis after operation.Experimental findings indicate that,tranexamic acid can effectively reduce postoperative blood loss and blood transfusion,as wel as number of blood transfusions after total knee arthroplasty.And it did not increase the risk of deep vein thrombosis.
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<p><b>OBJECTIVE</b>To compare the clinical results of early and delayed intramedullary nailing and locked plating for the treatment of multi-segments tibial fractures of type AO/ASIF-42C2.</p><p><b>METHODS</b>Between January 2010 and January 2013,45 patients with multi-segments closed tibial fractures of AO/ASIF-42C2 were treated by early primary intramedullary nailing and locked plating in 20 cases as early group and delayed in 25 cases as delayed group. In early group,20 cases included 13 males and 7 females with an average age of (37.9±14.3) years old ranging from 20 to 56 years;according to soft tissue injury Tscherne classification, 8 fractures were frade I,12 were grade II. In delayed group, 25 cases included 17 males and 8 females with an average age of (38.7±17.2) years old ranging from 24 to 55 years,4 fractures were grade I ,19 were grade II ,2 were grade III. The operative time, blood loss, hospital stay,fracture healing time and complications were recorded. At final follow-up, the Johner-Wruhs score were used to evaluate functional efficacy, and the posterior-anterior and lateral X-ray to evaluate fracture reduction and alignment.</p><p><b>RESULTS</b>All the patients were followed up for (12.5±2.5) months in early group and (13.2±2.8) months in delayed group (P>0.05). No wounds infections were happened. At the last follow-up, the mean range of knee joint was 10°-0°-120°. According to Johner-Wruhs scoring,there were 15 cases in excellent,3 in good,fair in 2 in early group; 21 in excellent,2 in good,2 in fair. The average operative time,blood loss had no significant differences between two groups (P>0.05), but hospital stay in early group was significantly shorter than those in delayed group(P<0.05). Average fracture healing time of early group and delayed group were (5.3±2.6) months and (6.0±2.9) months, respectively (P>0.05).</p><p><b>CONCLUSION</b>For multi-segments tibial fractures of type AO/ASIF-42C2 with preoperative minor soft tissue injuries lighter of Tscherne grade I or II, early primary intramedullary nailing and locked plating does not significantly increase the postoperative incidence of soft tissue complications for patients. The early and delayed primary intramedullary nailing and locked plating for treatment of AO/ASIF-42C2 proximal third tibial fractures can get similar curative effect.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Bone Plates , Fracture Fixation, Intramedullary , Methods , Tibial Fractures , General SurgeryABSTRACT
<p><b>OBJECTIVE</b>To verify the improving effect of transcutaneous electrical nerve stimulation (TENS) at Dingchuan (EX-B 1) on the pulmonary function of COPD patients at acute stage.</p><p><b>METHODS</b>Forty cases of COPD patients at acute stage were randomly divided into group A (20 cases) and group B (20 cases). TENS at Dingchuan (EX-B 1) with the frequency of 4 Hz and wave width of 200 ms was used in group A, and sham stimulation without current output at Dingchuan (EX-B 1) was used in group B. The changes of pulmonary function tests before and after treatment and the therapeutic effect after 10 days' treatment were observed and evaluated. The pulmonary function tests included forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and forced expiratory volume in one second to forced vital capacity ratio (FEV1 %).</p><p><b>RESULTS</b>There were no significant differences in all the pulmonary function indices between the two groups before treatment (all P > 0.05). There were also no significant differences in all the pulmonary function indices between the two groups after treatment (all P > 0.05). No statistical significance was obtained before and after treatment in each group (all P > 0.05).</p><p><b>CONCLUSION</b>The adjuvant therapeutic effect of TENS at Dingchuan (EX-B 1) with the frequency of 4 Hz and wave width of 200 ms on the pulmonary function indices of COPD patients at acute stage is not obvious.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Acupuncture Points , Acute Disease , Forced Expiratory Volume , Lung , Pulmonary Disease, Chronic Obstructive , Therapeutics , Transcutaneous Electric Nerve Stimulation , Vital CapacityABSTRACT
<p><b>OBJECTIVE</b>To study the status and influencing factors of malnutrition in rural children under 7 years of age in Gansu Province.</p><p><b>METHODS</b>By stratified random cluster sampling, 9 390 rural children under 7 years of age from 4 counties of Gansu Province were enrolled. A cross-sectional investigation on children's nutritional status was performed. The major influencing factors of malnutrition were evaluated by logistic regression analysis.</p><p><b>RESULTS</b>The detection rate of under-weight was 3.60% (338 cases). The growth retardation occurred in 992 cases (10.56%). Athrepsy was found in 196 cases (2.49%) out of 7 868 children under 5 years of age. Gender, age, birth weight, life style, parents' educational level and family income were influencing factors of malnutrition.</p><p><b>CONCLUSIONS</b>More attention should be paid to the issue of malnutrition of rural children under 7 years of age in Gansu Province. The prevalence of malnutrition may be reduced through increasing family income and nutrition education, and improving parents' education level and children's life style.</p>
Subject(s)
Child , Humans , Infant , Cross-Sectional Studies , Malnutrition , Epidemiology , Prevalence , Rural Population , Surveys and QuestionnairesABSTRACT
<p><b>BACKGROUND</b>Little is known about the role of dual angiotensin II forming pathways during heart failure. In the present study, the changes of chymase and angiotensin converting enzyme (ACE) expressions in the failing hearts of hamsters were analysed.</p><p><b>METHODS</b>Heart failure was induced by ligation of left anterior descending branch of the coronary artery. Chymase, ACE and angiotensin II type 1 receptor (AT1R) mRNA levels were analysed by reverse transcription polymerase chain reaction (RT-PCR). The activities of chymase and ACE were determined by radioimmunoassay (RIA). Myocardial collagen fibre analysis was performed under optical microscope.</p><p><b>RESULTS</b>Left ventricular systolic pressure (LVSP) and maximum left ventricular developed pressure increase rate (dp/dtmax, mmHg/s) gradually moved lower at 2, 3, 4 and 8 weeks after operation. On the other hand, left ventricular end-diastolic pressure (LVEDP) increased gradually after operation. Compared with the control group (3.55 +/- 0.06, 4.79 +/- 0.70), the heart weight/body weight ratio in operation group had increased significantly at 4 weeks and 8 weeks (4.28 +/- 0.43, 6.17 +/- 0.73) (P < 0.01). Collagen staining showed that the quantity of myocardial collagen fibre increased significantly in the operation group. RT-PCR showed that the chymase mRNA level in the operation group was consistently greater than that in the control group. AT1R mRNA level was also increased significantly at 3 weeks and 4 weeks, both being 1.3 times that of the control group (P < 0.01), whereas ACE mRNA level was not changed. Higher activity of chymase was detected in operation group, being 4, 8, 13 and 19 times that of the control group at 2, 3, 4 and 8 weeks (P < 0.01), respectively. ACE activity was also significantly higher at the same time, being 7, 10, 10 and 3.5 times that of the control (P < 0.01). Angiotensin II (Ang II) level in operation group increased significantly, being 2.5, 2.7, 3.5 and 2 times that of the control group at 2, 3, 4 and 8 weeks, respectively (P < 0.01).</p><p><b>CONCLUSIONS</b>A dual Ang II forming pathway from both ACE and chymase in the hamster hearts plays an important role during the development of heart failure. At the decompensatory stage, the reduction of AngII level may be associated with the decrease of ACE activity.</p>