OBJECTIVE:To investigate the protective effect of Tibetan medicine Compound Duoxuekang capsules on the acute lung injury in mice induced by lipopolysaccharide. METHODS:60 KM mice were randomly divided into blank group,model group,dexamethasone group (positive control,1 mg/kg) and Compound Duoxuekang high-dose,medium-dose,low-dose groups (3.6,1.8,0.9 g/kg,calculated by crude drug),10 in each group. Intragastrically administrated,mice in blank group and model group intragastrically administrated equal volume of normal saline,once a day. After 7 d of administration,except for blank group, mice in other groups intraperitoneally injected lipopolysaccharide to induce acute lung injury. After 6 h modeling,pathological changes in the lung tissue was observed,lung tissue water content was measured,superoxide dismutase(SOD),glutathione peroxi-dase(GSH-Px),malondialdehyde(MDA)levels in lung tissue and IL-6,TNF-α levels in serum were detected. RESULTS:Com-pared with blank group,mice in model group showed pathological changes in congestion and edema,inflammatory cell infiltra-tion,obvious widened alveolar septum and alveolar wall;water content in lung tissue and IL-6,TNF-αlevels in serum were signifi-cantly increased (P<0.01);SOD,GSH-Px levels in lung tissue were significantly decreased (P<0.01). Compared with model group,injury degree of lung tissue reduced to varying degrees in each treatment group,except for the water content,MDA level in lung tissue and TNF-α level in serum in Compound Duoxuekang capsules low-dose group;the above-mentioned indexes in other groups were significantly improved (P<0.05 or P<0.01). CONCLUSIONS:Compound Duoxuekang capsules can obviously re-duce mice's oxidative stress and inflammatory response,and has certain protective effect on acute lung injury in mice.

Defibrillation is the most effective method of treating ventricular fibrillation(VF), this paper introduces wearable automatic external defibrillators based on embedded system which includes EGG measurements, bioelectrical impedance measurement, discharge defibrillation module, which can automatic identify VF signal, biphasic exponential waveform defibrillation discharge. After verified by animal tests, the device can realize EGG acquisition and automatic identification. After identifying the ventricular fibrillation signal, it can automatic defibrillate to abort ventricular fibrillation and to realize the cardiac electrical cardioversion.
Animals ; Defibrillators ; Electric Countershock ; Electric Impedance ; Equipment Design ; Heart ; Humans ; Monitoring, Physiologic ; instrumentation ; Ventricular Fibrillation ; therapy

Objective To evaluate the efficacy and safety of adding neoadjuvant chemotherapy following neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer.Methods A total of 80 patients confirmed with locally advanced rectal cancer were enrolled during January 2012 and December 2015 in Guizhou Medical University Affiliated Cancer Hospital and were randomized with the method of lottery into the experimental group and the control group.In the experimental group,40 patients received 4 cycles of FOLFOX4 after chemoradiotherapy and then had total mesorectal excision (TME).Another 4 cycles of FOLFOX4 were administered after surgery.In the control group,40 patients had TME surgery 6-8 weeks after chemoradiotherapy and received 8 cycles of FOLFOX4 as adjuvant chemotherapy.Pelvic radiotherapy dose was 50 Gy in 25 fractions,5 days per week for 5 weeks.5-Fu continuous infusion was administered throughout radiotherapy.The pCR rate,downstaging rate,R0 resection rate,local recurrence rate,distant metastasis rate,survival rate,incidence of toxicities,surgical complications and completion of treatment were observed.Results The pCR rate was 20.0％ in the experimental group and 5.0％ in the control group (x2 =4.114,P ＜ 0.05).The downstaging rate was 77.4％ in the experimental group and 55.6％ in the control group(P ＞ 0.05).No statistically significant difference was observed in R0 resection rate,3-year local recurrence rate,3-year distant metastasis rate and 3-year survival rate between the two groups (P ＞ 0.05).Patients in the experimental group had higher completion rate of 8 cycles of systemic chemotherapy (87.1％ vs.61.5％,x2 =4.985,P ＜0.05).No statistically significant difference was observed in acute toxicities and postoperative complications.Conclusions Adding systemic chemotherapy after neoadjuvant chemoradiotherapy for locally advanced rectal cancer has significantly higher pCR rate and lower toxicities and side events compared with chemoradiotherapy alone.Longer follow-up and larger scale of clinical research are needed.Trial registration Chinese clinical trial registry,ChiCTR-IPR-17010454.

Objective To estimate the efficacy and safety of Voriconazole as antifungal prophylaxis of invasive fungal infection ( IFI) for malignant hematology patients. Methods The randomized controlled trials of Voriconazole treatment in invasive fungal infection for malignant hematology patients (ended in September 2014) were searched from Cochrane library, Medline, Embase, Pubmed, CBM, CNKI, Blood database. The meta analysis were performed by RevMan5.0. Results Ten literatures reported in 1 773 cases, in which there was significantly difference in effective rate between Voriconazole and other antifungal agents such as Amphotericin-B, Itraconazole, Micafungin and Fluconazole(P < 0.000 01); Four literatures indicated that there was significantly difference in adverse event rate between Voriconazole and amphotericin-B (P < 0.00 001); no significantly difference in adverse event rate between Voriconazole and amphotericin-B(P = 0.57); no significantly difference in adverse event rate between Voriconazole and Micafungin (P = 0.69); no significantly difference in adverse event rate between Voriconazole and Fluconazole (P = 0.70); Subgroup analysis indicated that adverse event rate between Voriconazole and Itraconazole is P=0.001, P = 0.17 respectively. Conclusion Voriconazole showed relative high efficient and low toxicity characteristics in treatment of malignant hematology accompanied by invasive fungal infection. But with its widely clinical application, the clinical value of Voriconazole needs to be further tested.

Objective To assess the outcomes of ischemic stroke patients with atrial fibrillation (AF).Methods Six thousand six hundred and ninety-five patients with acute ischemic stroke,admitted to our hospital from May 2005 to December 2013,were recruited consecutively.These patients were divided into combined AF group (n=583) and non-combined AF group (n=6112).The clinical data,including stroke subtypes,stroke severity,risk factors of stroke,NIHSS scores and Barthel index,and outcomes,including mortality,unfavourable prognosis and recurrence at 3,12,and 36 months after stroke were analyzed.Results The prevalence rate of AF in the patients enrolled in this study was 8.7％ (583/6695).There was a higher frequency of AF in female than that in male,with significant difference (45.8％ vs.33.0％,P＜0.05).The patients from combined AF group were older than those without AF.The percentage of severe stroke in AF patients (34.8％) was significantly higher than that in non-combined AF group (8.3％,P＜0.05).The patients with AF were less likely than the patients without AF to have hypertension (63.8％ vs.73.3％),diabetes (24.9％ vs.32.3％),dyslipidemias (26.1％ vs.31.5％),artery stenosis (17.2％ vs.23.4％),current smoking (22.6％ vs.39.0％),and alcohol consumption (7.5 ％ vs.18.9％),with significant differences (P＜0.05).After adjusting age,gender,stroke subtype,and severity,and risk factors,multivariate analysis showed that there was a higher recurrence risk in combined AF group at 3 months after stroke than that in non-combined AF group (P＜0.05);patients with AF had significantly higher mortality,dependency,and recurrence rates at 12 and 36 months after stroke than those without AF (P＜0.05).Conclusion The long-term prognosis of patients with stroke complicated with AF is poor;therefore,normalized anticoagulant therapy should be taken to decrease the recurrence rate and burdens of stroke in China.

OBJECTIVE: To determine the frequencies of deafness gene mutations among patients with non-syndromic hearing loss (NSHL) from northern Jiangsu province. METHODS: A total of 117 patients with NSHL were enrolled. The coding region of GJB2 gene, IVS7-2A>G and 2168A>G mutations of SLC26A4 gene, and 1555A>G and 1494C>T mutations of mitochondrial DNA 12S rRNA were subjected to Sanger sequencing. Patients in whom no mutation was detected were further tested by targeted gene capture and high-throughput sequencing. RESULTS: Among the 117 patients, 86 (73.50%) were found to carry mutations. GJB2 gene mutations were found in 61 patients (52.14%), including 22 (18.80%) with homozygous mutations and 39 (33.33%) with heterozygous mutations. SLC26A4 gene mutations were found in 19 patients (16.24%), including 4 (3.42%) with homozygous mutations and 15 with heterozygous mutations (14.53%). Mitochondrial 12S rRNA gene mutation was found in 6 patients (5.13%). Targeted gene capture and high-throughput sequencing of 8 patients identified 4 further cases, including 1 with RDX gene 129_130del and 76_79del compound heterozygous mutations, 1 with OTOF gene 1274G>C homozygous mutation, 1 with SLC26A4 gene 919-2A>G and IVS16-6G>A compound heterozygous mutation, and 1 with SLC26A4 gene 919-2A>G and A1673T compound heterozygous mutation. CONCLUSION The frequency of mutation among patients with NSHL from north Jiangsu was 73.50%, and GJB2 gene was most commonly mutated.
China ; Connexins ; DNA Mutational Analysis ; DNA, Mitochondrial ; Hearing Loss ; genetics ; Humans ; Membrane Proteins ; Mutation ; Sulfate Transporters

Objective To investigate the clinical severity,etiological classification and risk factors of severe cases with hand,foot and mouth disease (HFMD).Methods A total of 1 489 records on severe and fatal HFMD cases reported to the national pilot surveillance system of HFMD were used to analyze the demographic,medical treatment,etiological classification of the cases.Treatment outcome related risk factors were also studied with multi-variable stepwise logistic regression method.Results Seven out of the 1 489 severe HFMD cases died of this disease.A total of 960 (72.9％) were under three years old and 62.9％ were male and most of the cases (937,62.9％) resided in rural areas.Among all the cases,494 (33.2％) went to seek the first medical assistance at the institutions of village or township level.Durations between disease onset and first medical attendance,being diagnosed as the disease or diagnosed as severe cases were 0(0-1) d,1 (0-2) d and 2 (1-4) d,respectively.In total,773 (51.9％) of the severe HFMD cases were diagnosed as with aseptic meningitis,260 (17.5％) with brainstem encephalitis,377 (25.3 ％) with non-brainstem encephalitis,6 (0.4％) with encephalomyelitis,1 (0.1％) with acute flaccid paralysis,4 (0.3％) with pulmonary hemorrhage/pulmonary edema and 68 (4.6％) with cardiopulmonary failure.Of the etiologically diagnosed 1 217 severe and fatal HFMD cases,642 (52.8％) were with EV71,other enterovirus 261 (21.5％),Cox A16 36 (3.0％),1 (0.1％) with both EV71 and Cox A16.However,277 (22.8％) showed negative on any pathogenic virus.Complication (Z=3.15,P=0.002) and duration between onset and diagnosed as severe cases (Z=3.95,P＜0.001) were shown as key factors related to treatment outcomes.Conclusions Most severe HFMD cases appeared in boys,especially living in the rural areas.Frequently seen complications would include aseptic meningitis,non-brainstem encephalitis and brainstem encephalitis.EV71 was the dominant etiology for severe and fatal cases.Early diagnosis and complication control were crucial,related to the treatment outcome of HFMD.

Background: Interleukin-34 (IL-34) is an important immunomodulatory factor that plays a crucial role in a variety of autoimmune diseases. Aims: To investigate the expression of IL-34 in primary biliary cholangitis (PBC) and its influence on intrahepatic inflammation and bile duct damage. Methods: Liver tissues were obtained from 26 PBC patients and 10 hepatic hemangioma patients without PBC. Expression and localization of IL-34 were detected by immunohistochemistry. In animal experiment, Poly I:C intraperitoneal injection was used to construct PBC model in wild-type and IL-34-knockout C57BL/6 mice (WT-PBC group and IL-34KO-PBC group). Subsequently, the intrahepatic inflammation and bile duct damage were evaluated pathologically, and the expressions of IL-34 and associated cytokines in liver tissues were detected by real-time PCR and Western blotting. Results: Expression of IL-34 in liver tissues of PBC patients and PBC model mice was significantly higher as compared with those of the controls (all P<0.05). No morphological changes in hepatic pathological evaluation were observed in IL-34KO mice receiving intraperitoneal saline injection. In IL-34KO-PBC mice, the portal area inflammation and biliary epithelial cell damage were more severe than those in WT-PBC mice (all P<0.05). Expressions of proinflammatory cytokine interleukin-1β (IL-1β) and monocyte chemotactic protein-1 (MCP-1) in liver tissues of IL-34KO-PBC mice were significantly increased than those of WT-PBC mice, whereas expressions of antiinflammatory cytokine IL-10 and CD163, the surface marker of M2 macrophages, were significantly reduced (all P<0.05). Conclusions: IL-34 expression is increased in liver tissues of PBC patients and animals. It might reduce the portal area inflammation and bile duct damage via modulating cytokines expression and driving macrophages polarization to the M2 phenotype. IL-34 might act as a self-rescue factor which negatively regulates hepatic immune microenvironment and prevents disease progression.

OBJECTIVE: To explore the effect of advanced glycation end products (AGEs) on osteoclasts at different stages of differentiation. METHODS: Raw264.7 cells cultured were induced for osteoclastogenesis using RANKL, and the stages of differentiation of the osteoclasts were determined with TRAP staining. The cells were then randomly divided into control group, early-stage AGEs intervention group and late-stage AGEs intervention group. The viability of the cells after AGEs treatment was assessed using CCK-8 method. The cells were examined after the induction for osteoclastogenesis using TRAP staining, and the expression levels of RANK, NFATC-1, TRAF-6, TRAP and CTSK mRNAs were tested with RT-PCR; the expressions of CTSK and RANK proteins were detected using Western boltting. RESULTS: We defined the initial 3 days of induction as the early stage of differentiation and the time beyond 3 days as the late stage of differentiation of Raw264.7 cells. Intervention with AGEs at 100 mg/L produced no significant effects on the viability of the cells, but AGEs suppressed the cell proliferation at a concentration exceeding 100 mg/L. The number of osteolasts in the early- and late-stage intervention groups was greater than that in the control group, but the cell count differed significantly only between the early-stage intervention group and control group ( < 0.05). The gene expressions of RANK, NFATC-1, TRAF-6, TRAP and CTSK all increased after the application of AGEs in both the early and late stages of differentiation, but the changes were significant only in the early-stage intervention group ( < 0.05). The changes in CTSK and RANK protein expressions were consistent with their mRNA expressions. CONCLUSIONS AGEs can affect the differentiation of osteoclasts differently when applied at different stages, and intervention with AGEs at the early stage produces stronger effect to promote osteoclast differentiation than its application at a late stage.
Animals ; Bone Resorption ; Cell Differentiation ; Mice ; Osteoclasts ; RANK Ligand ; RAW 264.7 Cells ; Receptor Activator of Nuclear Factor-kappa B

OBJECTIVES: Excessive production of AGEs in diabetic patients will affect the normal function of osteoblasts, and this process may be related to autophagy of osteoblasts. This study aims to explore the effect of advanced glycation end products (AGEs) on autophagic activity during osteogenic differentiation in rat bone marrow mesenchymal stem cells (BMSCs). METHODS: BMSCs were isolated and cultured in vitro, treated with different concentrations (0, 50, 100, 200, and 400 mg/L) of AGEs for different time (3, 6, 12, 24, 48, and 72 h). The proliferation activity was detected by CCK-8 method. The mRNA and protein expression levels of Beclin1 and LC3 in cells were detected by real-time PCR and Western blotting, respectively.The autophagic vacuoles were observed under the transmission electron microscope. The cells were treated with autophagy promoter rapamycin or autophagy inhibitor 3MA. After 7 days of osteogenic induction, we performed alkaline phosphatase (ALP) staining and real-time PCR to detect the mRNA expression levels of osteogenesis-related genes. RESULTS: In the low-concentration groups, the proliferation activity in BMSCs was increased ( CONCLUSIONS Low concentration of AGEs can enhance the proliferative activity of BMSCs and promote osteogenic differentiation by accelerating autophagy. High concentration of AGEs can suppress the proliferation of BMSCs and inhibit osteogenic differentiation by reducing autophagy.
Animals ; Autophagy ; Bone Marrow Cells ; Cell Differentiation ; Cells, Cultured ; Glycation End Products, Advanced/pharmacology* ; Humans ; Osteoblasts ; Osteogenesis ; Rats ; Rats, Sprague-Dawley