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Ferroptosis (FPT), a novel form of programmed cell death, is characterized by overwhelming iron/reactive oxygen species (ROS)-dependent accumulation of lipid peroxidation (LPO). However, the insufficiency of endogenous iron and ROS level limited the FPT therapeutic efficacy to a large extent. To overcome this obstacle, the bromodomain-containing protein 4 (BRD4)-inhibitor (+)-JQ1 (JQ1) and iron-supplement ferric ammonium citrate (FAC)-loaded gold nanorods (GNRs) are encapsulated into the zeolitic imidazolate framework-8 (ZIF-8) to form matchbox-like GNRs@JF/ZIF-8 for the amplified FPT therapy. The existence of matchbox (ZIF-8) is stable in physiologically neutral conditions but degradable in acidic environment, which could prevent the loaded agents from prematurely reacting. Moreover, GNRs as the drug-carriers induce the photothermal therapy (PTT) effect under the irradiation of near-infrared II (NIR-II) light owing to the absorption by localized surface plasmon resonance (LSPR), while the hyperthermia also boosts the JQ1 and FAC releasing in the tumor microenvironment (TME). On one hand, the FAC-induced Fenton/Fenton-like reactions in TME can simultaneously generate iron (Fe3+/Fe2+) and ROS to initiate the FPT treatment by LPO elevation. On the other hand, JQ1 as a small molecule inhibitor of BRD4 protein can amplify FPT through downregulating the expression of glutathione peroxidase 4 (GPX4), thus inhibiting the ROS elimination and leading to the LPO accumulation. Both in vitro and in vivo studies reveal that this pH-sensitive nano-matchbox achieves obvious suppression of tumor growth with good biosafety and biocompatibility. As a result, our study points out a PTT combined iron-based/BRD4-downregulated strategy for amplified ferrotherapy which also opens the door of future exploitation of ferrotherapy systems.
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Liver fibrosis is a reversible pathological process caused by chronic liver damage and a major risk factor for hepatocellular carcinoma (HCC). Hepatic stellate cell (HSC) activation is considered the main target for liver fibrosis therapy. However, the efficiency of this strategy is limited due to the complex microenvironment of liver fibrosis, including excessive extracellular matrix (ECM) deposition and hypoxia-induced imbalanced ECM metabolism. Herein, nilotinib (NIL)-loaded hyaluronic acid (HA)-coated Ag@Pt nanotriangular nanozymes (APNH NTs) were developed to inhibit HSCs activation and remodel the microenvironment of liver fibrosis. APNH NTs efficiently eliminated intrahepatic reactive oxygen species (ROS) due to their inherent superoxide dismutase (SOD) and catalase (CAT) activities, thereby downregulating the expression of NADPH oxidase-4 (NOX-4) and inhibiting HSCs activation. Simultaneously, the oxygen produced by the APNH NTs further alleviated the hypoxic microenvironment. Importantly, the released NIL promoted collagen depletion by suppressing the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), thus synergistically remodeling the microenvironment of liver fibrosis. Notably, an in vivo study in CCl4-induced mice revealed that APNH NTs exhibited significant antifibrogenic effects without obvious long-term toxicity. Taken together, the data from this work suggest that treatment with the synthesized APNH NTs provides an enlightening strategy for remodeling the microenvironment of liver fibrosis with boosted antifibrogenic activity.
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The general practitioners are facing a series of issues in aspect of medical humanities:incomprehensive humanity care,insufficient subjective components in medical records,low service efficiency particularly during heavy work load in outpatient service.To adapt the challenges,a general hospital in Shanxi province had explored a pathway to integrate the medical social work into patient care in general practice since 2017.The medical social workers jointed the general practice team,involved in outpatient service and patient education,generated humanity records to improve the humanistic care,and to promote doctor-patient communication.The general medical services were significantly improved after the program implementation in the hospital.
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Objective@#To investigate the characteristics of acoustic impedance test and its diagnostic role for occupational noise induced deafness, in order to provide an objective basis for the differential diagnosis of occupational noise induced deafness.@*Methods@#A retrospective study was conducted to investigate the cases on the diagnosis of occupational noise-induced deafness in Guangdong province hospital for occupational disease prevention and treatment from January 2016 to January 2017. A total of 198 cases (396 ears) were divided into occupation disease group and non occupation disease group based on the diagnostic criteria of occupational noise deafness in 2014 edition, acoustic conductivity test results of two groups were compared including tympanograms types, external auditory canal volume, tympanic pressure, static compliance and slope.@*Results@#In the occupational disease group, 204 ears were found to have 187 ears (91.67%) of type A, which were significantly higher than those in the non occupational disease group 143/192 (74.48%) , the difference was statistically significant (χ2=21.038, P<0.01). Detection of Ad or As type, occupation disease group in other type were 16/204 (7.84%) , 3/204 (1.47%) , were lower than Ad or As type of occupation disease group (15.63%) , other type (9.38%) , the differences were statistically significant[ (χ2=5.834, P<0.05) , (χ2=12.306, P<0.01) ]. Occupation disease group canal volume average (1.68±0.39) ml higher than that of non occupation disease group (1.57±0.47) ml, the difference was statistically significant (t=2.756, P<0.01) ; occupation disease group mean static compliance (1.06±0.82) ml higher than that of non occupation disease group (0.89±0.64) ml. The difference was statistically singificant (t=2.59, P<0.01) .@*Conclusion@#We observed that acoustic impedance test had obvious auxiliary function in the differential diagnosis of occupational noise induced deafness, More than 90% of the confirmed cases showed an A-form tympanograms, it is one of the objective examination methods which can be used in the differential diagnosis of pseudo deafness.
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Inherited retinal diseases (IRDs), including retinitis pigmentosa, Usher syndrome, Cone-Rod degenerations, inherited macular dystrophy, Leber's congenital amaurosis, Leber's hereditary optic neuropathy are the most common and severe types of hereditary ocular diseases. So far more than 200 pathogenic genes have been identified. With the growing knowledge of the genetics and mechanisms of IRDs, a number of gene therapeutic strategies have been developed in the laboratory or even entered clinical trials. Here the progress of IRD research on the pathogenic genes and therapeutic strategies, particularly gene therapy, are reviewed.
Subject(s)
Humans , Biomedical Research , Methods , Clinical Trials as Topic , Genetic Predisposition to Disease , Genetics , Genetic Therapy , Methods , Mutation , Retinal Diseases , Genetics , Therapeutics , Treatment OutcomeABSTRACT
OBJECTIVE: To analyze the impact of GBZ 49-2014 Diagnosis of Occupational Noise-induced Deafness and GBZ49-2007 Diagnostic Criteria of Occupational Noise-induced Deafness on the diagnosis of occupational noise-induced deafness( ONID). METHODS: A total of 84 individuals,who were workers exposed to noise and diagnosed as observation subjects by GBZ 49-2007 were selected as the subjects of study by judgment sampling. They were diagnosed based on the criteria of GBZ 49-2014 and GBZ 49-2007. The impact of different diagnostic audiometry,different age and gender correction methods and the inclusion of a weighting of 0. 1 high-frequency 4. 0 k Hz hearing threshold of GBZ 49-2014 on the diagnosis of ONID was analyzed. RESULTS: The binaural high frequency threshold average( BHFTA) calculated by GBZ 49-2014 were lower than that of GBZ 49-2007 [( 52. 1 ± 10. 3) vs( 52. 8 ± 10. 1) d B,P < 0. 05 ],but monaural threshold of weighted value( MTWV) of the good ear calculated by GBZ 49-2014 were higher than speech frequency threshold average( SPTA) of the good ear of GBZ 49-2007 [( 23. 2 ± 4. 1) vs( 19. 3 ± 4. 8) d B,P < 0. 01]. All of the 84 patients had BHFTA ≥40 d B and SPTA < 26 d B when diagnosed by GBZ 49-2007,and could not be diagnosed as ONID. A total of33. 3% patients had BHFTA ≥40 d B and MTWV ≥26 d B when diagnosed by GBZ 49-2014 which could be diagnosed as mild ONID. The detection rate of ONID was 21. 4% to 34. 5%( P < 0. 01) when the threshold of 4. 0 k Hz was used as the weighting diagnostic threshold of hearing in the case of using different diagnostic audiograms and different age and sex correction methods. CONCLUSION: A high-frequency hearing threshold of 4. 0 k Hz with a weighting of 0. 1 was included in GBZ 49-2014 as a diagnostic threshold,which reduced the diagnostic threshold of ONID.
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Objective@#Study of the results and the degree on occupational noise-induced deafness in-to the different high frequency hearing threshold weighted value, in order to provide theoretical basis for the re-vision of diagnostic criteria on occupational noise-induced deafness.@*Methods@#A retrospective study was con-ducted to investigate the cases on the diagnosis of occupational noise-induced deafness in Guangdong province hospital for occupational disease prevention and treatment from January 2016 to January 2017. Based on the re-sults of the 3 hearing test for each test interval greater than 3 days in the hospital, the best threshold of each frequency was obtained, and based on the diagnostic criteria of occupational noise deafness in 2007 edition, Chi square test, t test and variance analysis were used to measure SPSS21.0 data, their differences are tested among the means of speech frequency and the high frequency weighted value into different age group, noise ex-posure group, and diagnostic classification between different dimensions.@*Results@#1. There were totally 168 cases in accordance with the study plan, male 154 cases, female 14 cases, the average age was 41.18 ±6.07 years old. 2. The diagnosis rate was increased into the weighted value of different high frequency than the mean value of pure speech frequency, the weighted 4 kHz frequency increased by 13.69% (χ2=9.880, P=0.002) , 6 kHz increased by 15.47% (χ2=9.985, P=0.002) and 4 kHz+6 kHz increased by15.47% (χ2=9.985, P=0.002) , the difference was statistically significant. The diagnostic rate of different high threshold had no obvious differ-ence between the genders. 3. The age groups were divided into less than or equal to 40years old group (A group) and 40-50 years old group (group B) , there were higher the diagnostic rate between high frequency weighted 4 kHz (A group χ2=3.380, P=0.050; B group χ2=4.054, P=0.032) , weighted 6 kHz (A group χ2=6.362, P=0.012; B group χ2=4.054, P=0.032) , high frequency weighted 4 kHz+6 kHz (A group χ2=6.362, P=0.012; B group χ2=4.054, P=0.032) than those of speech frequency average value in the same group on oc-cupational noise-induced deafness diagnosis rate, the difference was statistically significant. There was no sig-nificant difference between age groups (χ2=2.265, P=0.944) . 4. The better ear's mean value of pure speech fre-quency and the weighted values into different high frequency of working years on each group were compared, working years more than 10 years group was significantly higher than that of average thresholds of each frequen-cy band in 3-5 group (F=2.271, P=0.001) , 6-10 group (F=1.563, P=0.046) , the difference was statistically significant. The different high frequency weighted values were higher than those of the mean value of pure speech frequency, and the high frequency weighted 4 kHz+6 kHz had the highest frequency difference, with an average increase of 2.83 dB. 5. The diagnostic rate into weighted different high frequency was higher in the mild, moderate and severe grades than in the pure speech frequency. In the comparison of diagnosis for mild occupational noise-induced deafness, in addition to the weighted 3 kHz high frequency (χ2=3.117, P=0.077) had no significant difference, the weighted 4 kHz (χ2=10.835, P=0.001) , 6 kHz (χ2=9.985, P=0.002) , 3 kHz+4 kHz (χ2=6.315, P=0.012) , 3 kHz+6 kHz (χ2=6.315, P=0.012) , 4 kHz+6 kHz (χ2=9.985, P=0.002) , 3 kHz+4 kHz+6 kHz (χ2=7.667, P=0.002) were significantly higher than the diagnosis rate of the mean value of pure speech frequency. There was no significant difference between the two groups in the moderate and se-vere grades (P>0.05) .@*Conclusion@#Bring into different high frequency hearing threshold weighted value in-creases the diagnostic rate of occupational noise-induced deafness, the weighted 4 kHz, 6 kHz and 4 kHz+ 6 kHz high frequency value affects the result greatly, and the weighted 4 kHz+6 kHz high frequency hearing threshold value is maximum the effect on occupational noise-induced deafness diagnosis.
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Objective To explore the relationship between the objective indexes and TCM syndromes of occupational hand arm vibration disease ,and to provide clinical data for the objectification of TCM syndrome differentiation. Methods 101 patients with occupational hand arm vibration disease were collected ,including 24 patients with Xingbi,39 with Tongbi and 38 with Zhuobi,according to the theory of traditional Chinese medicine syndrome differentiation ,the relationship was observed between different TCM Syndrome types and various of parameters,such as 5-and 10-minute rewarming rates in cold water rewarming test,terminal latency,amplitude, conduction velocity ,average time ,average amplitude of abductor pollicis brevis and abductor digiti minimi in electromyography. Results 5-and 10-minute rewarming rate in cold water rewarming test did not differ significantly among the three groups(P > 0.05). Amplitude of median nerve motor conduction differed significantly among the three groups of Xingbi,Tongbi and Zhuobi(χ2 = 6.14,P < 0.05),Further comparison between the groups was made in Xingbi and Tongbi(χ2=0.132,P=0.895),Xingbi and Zhuobi(χ2=2.277,P=0.023),Tongbi and Xingbi (χ2 = 2.172 ,P = 0.030). There were no significant differences among the three groups in latency and conduction velocity of the median nerve motor conduction and latency ,amplitude and conduction velocity of ulnar nerve motor conduction(P>0.05). The differences of conduction velocity and amplitude of median nerve and ulnar nerve sensory conduction,average time and average amplitude of abductor pollicis brevis and abductor muscle among the three groups had no statistical differences(P>0.05). Conclusions The distribution is different in the amplitude of median nerve motor conduction among the three groups of Xingbi,Tongbi and Zhuobi,further analysis shows that the difference is mainly reflected in the Xingbi group. We conclude that the median nerve axonal injury is lighter in Xingbi group than in the other two groups.
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Objective To explore the relationship between the objective indexes and TCM syndromes of occupational hand arm vibration disease ,and to provide clinical data for the objectification of TCM syndrome differentiation. Methods 101 patients with occupational hand arm vibration disease were collected ,including 24 patients with Xingbi,39 with Tongbi and 38 with Zhuobi,according to the theory of traditional Chinese medicine syndrome differentiation ,the relationship was observed between different TCM Syndrome types and various of parameters,such as 5-and 10-minute rewarming rates in cold water rewarming test,terminal latency,amplitude, conduction velocity ,average time ,average amplitude of abductor pollicis brevis and abductor digiti minimi in electromyography. Results 5-and 10-minute rewarming rate in cold water rewarming test did not differ significantly among the three groups(P > 0.05). Amplitude of median nerve motor conduction differed significantly among the three groups of Xingbi,Tongbi and Zhuobi(χ2 = 6.14,P < 0.05),Further comparison between the groups was made in Xingbi and Tongbi(χ2=0.132,P=0.895),Xingbi and Zhuobi(χ2=2.277,P=0.023),Tongbi and Xingbi (χ2 = 2.172 ,P = 0.030). There were no significant differences among the three groups in latency and conduction velocity of the median nerve motor conduction and latency ,amplitude and conduction velocity of ulnar nerve motor conduction(P>0.05). The differences of conduction velocity and amplitude of median nerve and ulnar nerve sensory conduction,average time and average amplitude of abductor pollicis brevis and abductor muscle among the three groups had no statistical differences(P>0.05). Conclusions The distribution is different in the amplitude of median nerve motor conduction among the three groups of Xingbi,Tongbi and Zhuobi,further analysis shows that the difference is mainly reflected in the Xingbi group. We conclude that the median nerve axonal injury is lighter in Xingbi group than in the other two groups.
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Objective To investigate the value of emergency hysterectomy on arresting severe postpartum hemorrhage Methods A retrospective analysis was performed on 10 cases of hysterectomy by reason of postpartum hemorrhage between Jan 1990 and Dec 2000 Results All the patients were severe postpartum hemorrhage that couldn't be controlled by conservative treatment. Among them,there were 5 cases of DIC,2 cases of placental adherence,1 case each of uterine atony,uterine rupture and infection of uterine incision. Blood loss averaged 2 427 ml. All the 10 patients were recovered. Emergency hysterectomy was related to times of gestation and delivery and also to delivery pattern Conclusion Emergency hysterectomy is one of the effective methods on arresting severe postpartum hemorrhage.