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Objective:To learn about the characteristics of natural foci and the spatial distribution of mosquitoes and ticks in Yadong County, Tibet Autonomous Region (Tibet for short).Methods:The eco-geographical characteristics, demographic information, agricultural and animal husbandry data of the natural foci in Yadong County, Tibet were collected from the Yadong County 2020 statistical yearbook, vector data were collected from the Yadong County Center for Disease Control and Prevention, and the data of the meteorological station in Yadong County from 2010 to 2021 were collected from the World Weather Network. In July 2021, a total of 20 mosquito and tick sampling points were selected for field investigation according to the distribution characteristics of vegetation and animal husbandry of Yadong County. The light trap method was used to trap mosquitoes, and the manual inspection and flag dragging method were used to catch ticks. The spatial distribution characteristics of mosquitoes and ticks were analyzed.Results:The natural epidemic foci in Yadong County, Tibet, were high in the north and low in the south, with an elevation difference of about 5 000 m. It was rich in water resources, and the average runoff of Yadong River was 20.1 m 3/s. The climate in the north was cold and dry, and the south was mild and humid. From 2010 to 2021, the annual average station air pressure in Yadong County was 452.8 mmHg (1 mmHg = 0.133 kPa), the maximum monthly average temperature, precipitation and relative humidity of air were 8.7 ℃, 134.5 mm and 81.3%, respectively, all in July. A total of 6 897 diptera insects were attracted by the light trap method, all of which were non-blood-sucking mosquitoes. The total density was 163.77 pieces/(lamp·h), the dominant population was Muscaridae, accounting for 89.69% (6 186/6 897). In different sampling areas, Xiayadong Township collected the most mosquitoes, accounting for 67.17% (4 633/6 897); the others were Yadong County and Shangyadong Township, accounting for 27.36% (1 887/6 897) and 5.47% (377/6 897), respectively. A total 2 014 host animals were examined, and 23 parasitic ticks were caught, of which 20 were of the genus Ixodes and 3 were of the genus Haemophilus. No free ticks were caught in all ticks sampling points. Conclusions:The climate and ecological environment of the natural foci in Yadong County, Tibet have obvious vertical gradient. Mosquitoes and ticks are active, but the density is not high, the density of mosquitoes is generally high in the south and low in the north.
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Cholangiocarcinoma (CCA) has emerged as an intractable cancer with scanty therapeutic regimens. The aberrant activation of Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are reported to be common in CCA patients. However, the underpinning mechanism remains poorly understood. Deubiquitinase (DUB) is regarded as a main orchestrator in maintaining protein homeostasis. Here, we identified Josephin domain-containing protein 2 (JOSD2) as an essential DUB of YAP/TAZ that sustained the protein level through cleavage of polyubiquitin chains in a deubiquitinase activity-dependent manner. The depletion of JOSD2 promoted YAP/TAZ proteasomal degradation and significantly impeded CCA proliferation
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Objective To investigate the effect of argatroban in repair of spinal cord injury in rats.Methods A total of 54 female Wistar rats were selected and divided into three groups according to the random number table:sham group,injury group and Argatroban group,with 18 rats in each group.The sham group only took the T101amina;the injury group used the spinal cord injury device to make the rat spinal cord injury model;the Argatroban group received Argatroban treatment after spinal cord injury.The recovery of hindlimb motor function was evaluated by BBB score and clined plate test before injury and 7,14,21,28,35 and 42 days after injury.The sensory evoked potentials (SEP) and motor evoked potentials (MEP) were detected 42 days after operation.HE staining was used to compare the size of the cavity in the local region 42 days after injury.Results At day 7 after injury,the BBB score was (3.7 ±0.5) points and the inclined plane test was (28.0 ± 2.6) ° in the Argatroban group,which were better than those in the injury group [(3.3 ± 0.5) points,(24.3 ± 1.9) °] (p ＜ 0.05).At day 42 after injury,the BBB score was (13.0 ± 0.8) points and inclined plane test was (50.7 ± 2.7) ° in the Argatroban group,which were significantly better than those in the injury group [(9.7 ± 1.3) points,(40.5 ± 2.7)°] (p ＜0.05).But all the above values in the Argatroban group were significantly lower than those in the sham group [(21.0 ± 0.0) points,(60.0 ± 0.0) °] (P ＜ 0.05).At day 42 after operation,the SEP latency [(25.0 ± 0.9)ms] in the Argatroban group was significantly shorter than that in the injury group [(31.5 ± 1.9) ms];the amplitude [(2.1 ± 0.1) μV] in the Argatroban group was lower than that in the injury group [(0.5 ± 0.1) μV] (P ＜ 0.05).The MEP latency [(11.5 ± 1.0) ms]in the Argatroban group was significantly shorter than that in the injury group [(17.5 ± 1.1) ms],and the amplitude [(4.8 ± 0.8) μV] in the Argatroban group was lower than that in the injury group [(2.8 ± 0.7) μV] (P ＜ 0.05).And the SEP or MEP latency and amplitude in the Argatroban group showed significant differences compared to the sham group [(7.5 ± 1.0) ms,(7.5 ± 1.0) μV] (P ＜0.05) . HE staining showed that the central area of the lesion in the Argatroban group [(0.35 ± 0.04) mm2]was significantly smaller than that in the injury group [(0.71 ± 0.05)mm2].Conclusion After spinal cord injury,argatroban can protect the spinal cord tissue effectively in the injured area and promote recovery of sensory and motor function in the hind limbs of rats.
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Objective:To investigate the current situation of general practitioners' occupational pressure in Heilongjiang Province, and explore its relationship with professional identity and perceived organizational support. It aims to provide references for the construction of general practitioners and the development of general medical education.Methods:The general situation questionnaire, perceived organizational support scale, occupational pressure scale, and professional identity scale were applied through network and site surveys for collecting data. A total of 288 questionnaires were collected with 263 valid questionnaires (91.3%). Pearson correction analysis and bootstrap analysis were performed for data analysis.Results:The average score of occupational pressure among general practitioners was (115.95±22.40), and the results of Pearson correction analysis showed that perceived organizational support was negatively correlated with occupational pressure ( r=-0.413, P<0.01) and positive correlation with professional identity ( r=0.587, P<0.01). There were also significant negative correlations between professional identity and occupational pressure ( r=-0.442, P<0.01). Moreover, the mediating effect showed that professional identity had a certain mediating effect on the relationship between perceived organizational support and occupational pressure (LLCI=-0.2039, ULCI=-0.0760, P<0.05). Conclusion:General practitioners' occupational pressure was at a high level, which can be reduced through improving the perceived organizational support and professional identity.
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Objective@#To investigate the effect of argatroban in repair of spinal cord injury in rats.@*Methods@#A total of 54 female Wistar rats were selected and divided into three groups according to the random number table: sham group, injury group and Argatroban group, with 18 rats in each group. The sham group only took the T10lamina; the injury group used the spinal cord injury device to make the rat spinal cord injury model; the Argatroban group received Argatroban treatment after spinal cord injury. The recovery of hindlimb motor function was evaluated by BBB score and clined plate test before injury and 7, 14, 21, 28, 35 and 42 days after injury. The sensory evoked potentials (SEP) and motor evoked potentials (MEP) were detected 42 days after operation. HE staining was used to compare the size of the cavity in the local region 42 days after injury.@*Results@#At day 7 after injury, the BBB score was (3.7±0.5)points and the inclined plane test was (28.0±2.6)° in the Argatroban group, which were better than those in the injury group [(3.3±0.5)points, (24.3±1.9)°] (P<0.05). At day 42 after injury, the BBB score was (13.0±0.8)points and inclined plane test was (50.7±2.7)° in the Argatroban group, which were significantly better than those in the injury group [(9.7±1.3) points, (40.5±2.7)°] (P<0.05). But all the above values in the Argatroban group were significantly lower than those in the sham group [(21.0±0.0)points, (60.0±0.0)°](P<0.05). At day 42 after operation, the SEP latency [(25.0±0.9)ms] in the Argatroban group was significantly shorter than that in the injury group [(31.5±1.9) ms]; the amplitude [(2.1±0.1)μV] in the Argatroban group was lower than that in the injury group [(0.5±0.1)μV] (P<0.05). The MEP latency [(11.5±1.0)ms] in the Argatroban group was significantly shorter than that in the injury group [(17.5±1.1)ms], and the amplitude [(4.8±0.8)μV] in the Argatroban group was lower than that in the injury group [(2.8±0.7)μV] (P<0.05). And the SEP or MEP latency and amplitude in the Argatroban group showed significant differences compared to the sham group [(7.5±1.0)ms, (7.5±1.0)μV](P<0.05). HE staining showed that the central area of the lesion in the Argatroban group [(0.35±0.04)mm2] was significantly smaller than that in the injury group [(0.71±0.05)mm2].@*Conclusion@#After spinal cord injury, argatroban can protect the spinal cord tissue effectively in the injured area and promote recovery of sensory and motor function in the hind limbs of rats.
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Hypoxia is a common feature of solid tumors. As transcription factors, hypoxia-inducible factors (HIFs) are the master regulators of the hypoxic microenvironment; their target genes function in tumorigenesis and tumor development. Intriguingly, both yes-associated protein (YAP) and its paralog transcriptional coactivator with a PDZ-binding motif (TAZ) play fundamental roles in the malignant progression of hypoxic tumors. As downstream effectors of the mammalian Hippo pathway, YAP and/or TAZ (YAP/TAZ) are phosphorylated and sequestered in the cytoplasm by the large tumor suppressor kinase 1/2 (LATS1/2)-MOB kinase activator 1 (MOB1) complex, which restricts the transcriptional activity of YAP/TAZ. However, dephosphorylated YAP/TAZ have the ability to translocate to the nucleus where they induce transcription of target genes, most of which are closely related to cancer. Herein we review the tumor-related signaling crosstalk between YAP/TAZ and hypoxia, describe current agents and therapeutic strategies targeting the hypoxia-YAP/TAZ axis, and highlight questions that might have a potential impact in the future.
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This study reported two women with extreme obesity who underwent metabolic surgery due to their mutations in leptin receptor (LEPR).Genomic DNA was extracted from the anticoagulant blood samples of the two patients and their parents.A panel of genes related to metabolic diseases or whole exon sequencing was screened and the results were confirmed by Sanger sequencing.This is the first time that these three mutations in LEPR were reported.Two patients complained insatiety and early-onset obesity since childhood at clinics.Patient 1 was a 39-year-old woman with height 150 cm,weight 130 kg,and BMI 57.8 kg/m2.Serum leptin level was 156.4 μg/L.A homozygous mutation of c.2317G＞T was found in exon 15 of LEPR gene in patient 1,which was descended from her father and mother respectively.Patient 2 was a 37-year-old woman with height 158 cm,weight 167 kg,and BMI 67 kg/m2.Serum leptin level was 193.4 μg/L.Genetic analysis showed compound heterozygous mutations of c.1482delT and c.1892C ＞ A.Her father showed heterozygous c.1482delT mutation,and her mother carried heterozygous c.1892C ＞ A mutation.Two patients all underwent metabolic surgery with body weight reduction of about 22 kg and 40 kg respectively after first six months.However,the follow-up studies showed that the body weight of patient 1 rebounded to pre-surgery level in two years and patient 2 did not further lose weight in the following six months.
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Monoclonal antibodies (mAbs) are widely used in many fields due to their high specificity and ability to recognize a broad range of antigens. IL-17A can induce a rapid inflammatory response both alone and synergistically with other proinflammatory cytokines. Accumulating evidence suggests that therapeutic intervention of IL-17A signaling offers an attractive treatment option for autoimmune diseases and cancer. Here, we present a combinatorial approach for optimizing the affinity and thermostability of a novel anti-hIL-17A antibody. From a large naïve phage-displayed library, we isolated the anti-IL-17A mAb 7H9 that can neutralize the effects of recombinant human IL-17A. However, the modest neutralization potency and poor thermostability limit its therapeutic applications. affinity optimization was then used to generate 8D3 by using yeast-displayed random mutagenesis libraries. This resulted in four key amino acid changes and provided an approximately 15-fold potency increase in a cell-based neutralization assay. Complementarity-determining regions (CDRs) of 8D3 were further grafted onto the stable framework of the huFv 4D5 to improve thermostability. The resulting hybrid antibody 9NT/S has superior stabilization and affinities beyond its original antibody. Human fibrosarcoma cell-based assays and analyses in mice indicated that the anti-IL-17A antibody 9NT/S efficiently inhibited the secretion of IL-17A-induced proinflammatory cytokines. Therefore, this lead anti-IL-17A mAb might be used as a potential best-in-class candidate for treating IL-17A related diseases.
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Objective To evaluate the efficacy of Qingfei-Jiedu decoction in the treatment of Acne. Methods A total of 93 female patients with acne were randomly divided into 3 groups according to random number table, 31 in each group. The observation group took the oral Qingfei-Jiedu decoction, and the Chinese medicine control group took the oral tanshinone capsule, and the western medicine control group took the oral acetic acid ring propyl alcohol progesterone. All 3 groups were treated for 4 weeks. The levels of serum dihydro (DHT), IL-6 and IL-8 were measured by ELISA. The changes of the lesions before and after treatment were observed and the adverse events were recorded during the treatment. The clinical effect was evaluated. Results After treatment, the serum DHT (56.94 ± 15.74 pg/ml vs. 74.48 ± 18.53 pg/ml, t=2.089), IL-6 (22.84 ± 11.77 pg/ml vs. 30.37 ± 14.50 pg/ml, t=2.135), IL-8 (22.64 ± 7.38 pg/ml vs. 29.54 ± 9.65 pg/ml, t=2.057) in the observation group were significantly lower than those in the Chinese medicine control group (P<0.05). After treatment, the disappearance rate of skin lesions (65.4% ± 15.0% vs. 44.7% ± 12.9%, 42.7% ± 13.6%, F=6.862) and comprehensive syndrome effective rate (57.2% ± 12.6% vs. 46.3% ± 12.8%, 44.8% ± 11.7%, F=5.322) in the observation group were significantly higher than those in the other two control groups (P<0.05). The observation group and the traditional Chinese medicine control group did not have adverse events, but the western medicine control group showed one case nausea. Conclusions The Qingfei-Jiedu decoction can reduce the level of serum DHT, IL-6 and IL-8 in female patients with acne vulgaris, and improve the skin lesion disappearance rates and comprehensive syndrome rates.
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In this paper, carbon nanotubes [CNTs] were added into chitosan [CS] hydrogels in the form of chitosan modified CNTs [CS-CNTs] composites to prepare carbon nanotubes hydrogels [CNTs-GEL]. The products, named CS-MWCNTs, were characterized by scanning electron microscope [SEM] and Fourier transform infrared [FTIR] spectroscopy. Swelling properties and effect of pH on controlled release performance of the two kinds of hydrogels, CNTs-GEL and pure chitosan hydrogels without CNTs [GEL], were investigated respectively. The results showed that CNTs-GEL possess better controlled release performance than GEL. The releasing equilibrium time of CNTs-GEL was longer than that of GEL in both pH = w7.4 and pH=1.2 conditions, although the release ratios of the model drug are similar in the same pH buffer solutions. It is found that release kinetics is better fitted Ritger-Peppas empirical model indicating a fick-diffusion process in pH = 1.2, while in pH = 7.4 it was non-fick diffusion involving surface diffusion and corrosion diffusion processes