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Rodent-infested bald spots are crucial indicators of rodent infestation in grasslands. Leveraging Unmanned Aerial Vehicle (UAV) remote sensing technology for discerning detrimental bald spots among plateau pikas has significant implications for assessing associated ecological hazards. Based on UAV-visible light imagery, we classified and recognized the characteristics of plateau pika habitats with five supervised classification algorithms, i.e., minimum distance classification (MinD), maximum likelihood classification (ML), support vector machine classification (SVM), Mahalanobis distance classification (MD), and neural network classification (NN) . The accuracy of the five methods was evaluated using a confusion matrix. Results showed that NN and SVM exhibited superior performance than other methods in identifying and classifying features indicative of plateau pika habitats. The mapping accuracy of NN for grassland and bald spots was 98.1% and 98.5%, respectively, with corresponding user accuracy was 98.8% and 97.7%. The overall model accuracy was 98.3%, with a Kappa coefficient of 0.97, reflecting minimal misclassification and omission errors. Through practical verification, NN exhibited good stability. In conclusion, the neural network method was suitable for identifying rodent-damaged bald spots within alpine meadows.

In high energy heavy-ion collisions, the high speed valence charges will produce intense electromagnetic fields within the resulting quark-gluon plasma. Utilizing the AMPT model, this paper presents a comprehensive analysis of the magnetic field distribution generated from non-central collisions between [Formula: see text] nuclei at [Formula: see text]. The initial geometric parameters of the collision and the electric conductivity of the quark-gluon plasma have a dominant influence on the evolution of the magnetic field, while the plasma diffusion and the CME effect have a lesser impact and only slightly involve the original magnetic field by inducing new magnetic fields. This finding suggests that the dynamics of the quark-gluon plasma can be roughly decoupled from the effect of the electromagnetic field., (© 2023. The Author(s).)

Ligularia virgaurea and Ligularia sagitta are two species of poisonous plants with strong invasiveness in natural grasslands in China that have caused considerable harm to animal husbandry and the ecological environment. However, little is known about their suitable habitats and the key environmental factors affecting their distribution. Although some studies have reported the distributions of poisonous plants on the Qinghai-Tibet Plateau (QTP) and predicted their potential distributions at local scales in some regions under climate change, there have been few studies on the widespread distributions of L. virgaurea and L. sagitta . In this study, we recorded 276 and 118 occurrence points of L. virgaurea and L. sagitta on the QTP using GPS, and then used the MaxEnt model to predict the distribution of suitable habitats. Results showed that (1) under current climate conditions, L. virgaurea and L. sagitta are mainly distributed in southern Gansu, eastern Qinghai, northwestern Sichuan, eastern Tibet, and southwestern Yunnan, accounting for approximately 34.9% and 39.8% of the total area of the QTP, respectively; (2) the main environmental variables affecting the distribution of suitable habitats for L. virgaurea and L. sagitta are the Human Footprint Index (52.8%, 42.2%), elevation (11%, 4.4%), soil total nitrogen (18.9%, 4.2%), and precipitation seasonality (5.1%, 7.3%); and (3) in the future, in the 2050s and 2070s, the area of habitat of intermediate suitability for L. virgaurea will spread considerably in northwest Sichuan, while that of high suitability for L. sagitta will spread to eastern Tibet and western Sichuan., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dong, Hua, Hua, Ye, Bao, Cai, Cai, Zhao, Chu and Tang.)

In this study, we aimed to investigate treatment options and the prognosis of patients with WM in China. This retrospective study included 1141 patients diagnosed with symptomatic WM between January 2003 and December 2019 at 35 tertiary hospitals in 22 provinces of China. Fifty-four patients (7.3%) received monotherapy, 264 (36.0%) received chemoimmunotherapy, 395 (53.8%) received other combination regimens without rituximab, and 21 (2.9%) received ibrutinib. Using a multivariable Cox regression model, age > 65 years old, platelets <100 × 10 9 /L, serum albumin <3.5 g/dl, β2 microglobulin concentration ≥4 mg/L and LDH ≥250 IU/L predicted poor OS. In summary, our study showed that frontline treatment choices for WM are widely heterogeneous. We validated most of the established prognostic factors in the rIPSS (age >65 years, LDH ≥250 IU/L, ALB <3.5 g/dl and β2 microglobulin ≥4 mg/L) together with PLT ≤ 100 × 10 9 /L indicate a poor prognosis for patients with WM.

Objective: To evaluate the efficacy and safety profile of ixazomib/lenalidomide/dexamethasone (IRd) in Chinese patients with relapsed/refractory multiple myeloma (MM) . Methods: This study comprising 14 medical centers in China included patients with relapsed/refractory MM who received at least. Ixazomib at an initial oral dose of 4 mg was administered. Seven patients had dose adjustment to 3 mg at the time of first dose. The lenalidomide doses were adjusted according to creatinine clearance rate. The efficacy and safety were evaluated every cycle. Results: In the study cohort of 74 patients, the median age was 65 years and 11 (14.9% ) patients received over three lines of therapy. Overall response rate (ORR) was 54.1% (40/74) , and 7 (9.5% ) , 14 (18.9% ) , and 19 (25.7% ) patients achieved stringent complete response or complete response, very good partial response, and partial response, respectively. The median progression-free survival and overall survival were 9.9 and 20 months, respectively. The median time to response was 1 month. The efficacy and survival outcome were similar to those reported in the Tourmaline-MM1 China Continuous Study. The ORR of patients refractory to bortezomib, lenalidomide, and bortezomib plus lenalidomide were 52.0% (13/25) , 57.1% (4/7) , and 33.3% (6/18) , respectively. The rate of grade 3-4 adverse events was 36.5% (27/74) . Common hematological toxicities were anemia, thrombocytopenia, lymphopenia, and neutropenia. Common non-hematological toxicities were fatigue, gastrointestinal symptoms, and infections. Two cases of grade 3 peripheral neuropathy were reported. The patients eligible for the Tourmaline-MM1 China Continuous Study had a higher ORR than the ineligible patients [77.8% (14/18) vs 46.4% (26/56) , P =0.020]. There was no difference in the rate of grade 3-4 adverse events [33.3% (6/18) vs 37.5% (21/56) , P =0.749]. Conclusion: The IRd regimen had good efficacy and acceptable toxicity in Chinese patients with relapsed/refractory MM.

Background: Recent studies have reported that low-income adults living in more affluent areas of the United States have longer life expectancies. Less is known about the relationship between the affluence of a geographic area and morbidity of the low-income population., Objective: To evaluate the association between the prevalence of chronic conditions among low-income, older adults and the economic affluence of a local area., Design: Cross-sectional association study., Setting: Medicare in 2015., Participants: 6 363 097 Medicare beneficiaries aged 66 to 100 years with a history of low-income support under Medicare Part D., Measurements: Adjusted prevalence of 48 chronic conditions was computed for 736 commuting zones (CZs). Factor analysis was used to assess spatial covariation of condition prevalence and to construct a composite condition prevalence index for each CZ. The association between morbidity and area affluence was measured by comparing the average of condition prevalence index across deciles of median CZ house values., Results: The mean age of study participants was 77.7 years (SD, 8.2); 67% were women, and 61% were white. The crude prevalence of 48 chronic conditions ranged from 72.5 per 100 for hypertension to 0.6 per 100 for posttraumatic stress disorder. The prevalence of these 48 chronic conditions was highly spatially correlated. Composite condition prevalence was on average substantially lower in more affluent CZs., Limitation: Low-income status measured on the basis of receipt of Medicare Part D low-income subsidies and not capturing persons not enrolled in Medicare Part D., Conclusion: Low-income, older adults living in more affluent areas of the country are healthier, and areas with poor health in the low-income, older adult population tend to have a high prevalence of most chronic conditions., Primary Funding Source: National Institute on Aging.

Objective: To investigate the phenotype and molecular mechanism of DCA on MDS cell model, and to study the response of chemotherapeutic medicines to MDS cells through multiple dimensions, such as cell proliferation, invasion, migration and apoptosis, thus revealing the molecular mechanism of DCA treatment of MDS and its relationship with SHP-1 gene methylation., Methods: MTT assay was used to determine the survival rate of MDS cells after treated by different concentrations of DCA. The effect of DCA on the invasion and migration of MDS cells was detected by Transwell assay method. Apoplexin V-FITCPI was used to detect apoptosis, the MDS treatment on the mechanism of DCA was investigated by Western blot and Real-time PCR experiment., Results: According to the experiment, it was found that tumor proliferation could be inhibited when MDS skm-1 cells was treated by DCA, and the absorbance was lower and the inhibitory effect was more obvious in the 2.0, 5.0 μmol/L DCA group than in the 0.5 μmol/L DCA group and the negative control group. Compared with the control group, the number of MDS skm-1 cells crossing through the transwell upper chamber was significantly decreased after DCA application. After treated with 0.5, 2.0 and 5.0 μmol/L DCA, the apoptosis rate of MDS cells was 4.54%, 9.31% and 16.58% respectively, while the apoptosis rate of the control group was 3.20%, which shows the apoptosis rate increased significantly with the concentration of DCA. After treatment of MDS cell lines with different concentration of DCA, the methylation status of SHP-1 gene was decreased with the increase of drug concentration, the expression of SHP-1 was increased, the expression of STAT3 was decreased and the level of phosphorylation was decreased., Conclusion: By analyzing the phenotypic response of DCA treatment on MDS cells, it was found that interfere with MDS can be performed by inhibiting proliferation, metastasis, and inducing apoptosis in a dose-dependent way. It revealed that the molecular mechanism by DCA treatment can improve the methylation of SHP-1 gene and inhibit the expression of p-STAT3.

Objective: To assess the methylation level of SHP-1 promoter region and the effects on the phosphorylation of the Signal Transducers and Activators of Transcription 3 (STAT3) protein in bone marrow specimen of patients with myelodysplastic syndrome (MDS), and to explore the relationship of SHP-1 methylation and prognosis of the patients. Method: Bone marrow specimens of 93 patients with MDS were collected from the General Hospital of Tianjin Medical University from September 2010 to June 2014. The enrolled subjects included 54 males and 39 females and they were divided into the low-risk group (IPSS score:0-1.0, median: 0.5) and the high-risk group (IPSS score: 1.5-3.0, median: 2.5) according to the International Prognostic Score System (IPSS). The methylation level of SHP-1 was detected by methylation-specific polymerase chain reaction, and the level of p-STAT3 was detected using Western blot. Results: In the high-risk group, 64.44% (29/45) of the patients had methylation in the SHP-1 promoter region, which was significantly higher than the low-risk group 22.92% (11/48). Therefore, SHP-1 methylation was frequently presented in the patients of the high-risk group. Similarly, 66.67% (30/45) of the patients in the high-risk group had positive STAT3 phosphorylation status, whereas only 20.83% (10/48) were tested positive in the low-risk group. In addition, correlation analysis also revealed that the SHP-1 methylation rate was positively correlated with the positive rate of STAT3 phosphorylation ( r= 0.57, P< 0.001). Conclusions: SHP-1 methylation is significantly correlated with the risk of MDS patients. It may be used as an independent predictor of shorter survival in patients of the high-risk group. The increased level of SHP-1 methylation will lead to the uncontrolled activation of the downstream JAK/STAT3 pathway, which in turn can cause further positive feedback to amplify the carcinogenic signal.

Objective: To investigate a reliable clinical indication for predicting the therapeutic response of decitabine therapy in the patients with myelodysplastic syndromes (MDS)., Methods: The clinical efficacy of decitabine for 55 cases of MDS was analyzed retrospectively. According to the lymphocyte level at d28 after the first time treatment with decitabine, the patients were divided into high lymphocyte level group (H-Lym≥1.2×10 9 /L) and low lymphocyte level group (L-Lym<1.2×10 9 /L), and the overall response rate (ORR) and the progression-free survival (PFS) time in 2 groups were compared., Results: As compared with L-Lym group, the ORR and PFS time in H-Lym group were significantly enhanced ［(76.0% vs 50.0%) (P<0.05) and median time (15.7 months vs 8.5 months)(P<0.05), respectively］;the ratio of platelet level ≥100×10 9 /L in H-Lym group was very significantly higher than that in L-Lym group (72.0% vs 20.0%)(P<0.01). Multivariat analysis showed that the risk of disease progression in L-Lym group was 4.45-fold of H-Lym group (95% CI:1.58-12.59)(P<0.05)., Conclusion: The patients with lymphocyte level ≥1.2×10 9 /L at day 28 after the first time treatment with decitabine show the higher ORR and longer PFS time, therefore. the lymphocyte level at day 28 after first time treatment with decitabine can be used as an early clinical indicator for predecting the response to decitabine treatment.

Hypomethylating agents(HMA) currently are widely used in the treatment of myelodysplastic syndromes (MDS), provide a significant improvement in the treatment of MDS. However, resistance to HMA is an almost universal phenomenon. This review was focused on immune effects related to DNA methylation, and to explore the mechanism underlying HMA resistance involved in immune checkpoint pathways. However, the optimal role of checkpoint blockade therapy (CBT) and immune checkpoint pathways remain in HMA failure questionable. The better understanding of immune checkpoint pathways in resistance of HMA offers a compelling rationale to introduce CBT in patients as a novel treatment option. CBT is an established strategy in solid tumors with potential as an adjunctive therapy in hematologic malignancies, therefore, may alter the treatment landscape in MDS. The suitability and effectiveness of combining HMA with CBT need to be confirmed by the results of ongoing clinical trials, so as to find novel strategies to improve outcome after failure of HMA.

The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal myeloid disorders characterized by ineffective hematopoiesis and increased risk of transformation to acute myelogenous leukemia (AML). The treatment of MDS is highly dependent on the reliability of the prognostic evaluation model. Current clinical prognostic scoring systems are comprised of morphology, pivotal clinical trials and cytogenetic findings. However, none of the available prognostic systems incorporates disease-related molecular abnormalities, such as somatic mutations. Cumulative evidence suggests that genomic data can also be used clinically to assist the diagnosis, prognosis, prediction of response to specific therapies, and the development of novel and accurate targeted therapies. Therefore, it is not possible to predict the response of patients to molecular targeted drugs, such as demethylation drugs. With the recent advance in whole- genome sequencing technologies, cumulative evidence suggests that genomic data can also be associated with the genesis, prognosis, prediction of response to specific therapies, and the development of novel accuvate targeted therapies, the issue of having some mechanism to dissect this heterogeneity and precision treatment is coming to the fore. However, there are still several hindrances to its clinical application. If these problems can be solved, molecular genetics will further provide a theoretical basis for the application of precision medicine in MDS.

Objective: To investigate the effects of absolute lymphocyte count(ALC) before start of the first cycle of consolidation chemotherapy(CC) on the relapse free survival in the patients with acute myeloid leukemia(AML), so as to explore a simple and easy method for predicting AML relapse., Methods: The clinical data of 132 patients with newly diagnosed AML (all non-acute promyelotic leukemia) from 2011 to 2017 were analyzed retrospectively. The 132 AML patients were treated with standard induction chemotherapy (IC) and consolidation chemotherapy (CC). According to lymphocyte count of patients before start of the first cycle of CC, the AML patients were divided into 2 group: high lymphocyte count group (H-Lym≥1.2×10 9 /L) and low lymphocyte count group (L-Lym<1.2×10 9 /L). The differences in ralapse rate and relapse-free survival between 2 groups were analyzed., Results: Among 132 patients with AML, patients who could be valuated and were elicible for the study accounted for 65 (49.24%). The absolute leukocyte count, age, chromosome karyotypes before IC of patients did not show statistical difference between H-Lym group (40 cases) and L-Lym group (25 cases). Unvarvate analysis showed that the Low lymphocyte count and unfavorable chromosome karyotypes were poor prognostic factors for the relapse-free survival time, and there was significant difference between 2 groups (P<0.01). The relapse risk in patients of L-Lym group increased, the hazard ratio (HR)=3.01 (95% CI=1.55-4.98) (P<0.01). In multivariate analysis containing unfavorable prognostic karyotypes, this trend still existed (HR=2.52, 95% CI 1.28-9.98)(P<0.01)., Conclusion: The AML patients with high lymphocyte count before the first CC have more long relapse free survival time suggesting that the lymphocyte count before the first CC may be prognostic factor for relapse free survival of AML patients.

The Affordable Care Act (ACA) has increased the number of Americans with health insurance. Yet many policy makers and consumers have questioned the value of Marketplace plan coverage because of the generally high levels of cost sharing. We simulated out-of-pocket spending for bronze, silver, or gold Marketplace plans (those having actuarial values of 60 percent, 70 percent, and 80 percent, respectively). We found that for the vast majority of consumers, the proportion of covered spending paid by the plans is likely to be far less than their actuarial values, the metric commonly used to convey plan generosity. Indeed, only when annual health care spending exceeds $16,500 for bronze plans, $19,500 for silver plans, and $21,500 for gold plans do plans in these metal tiers cover the proportion of costs matching their actuarial values. While Marketplace plans substantially reduce consumers' exposure to financial risk relative to being uninsured, the use of actuarial values to communicate plan generosity is likely to be misleading to consumers.

The research selected the alpine meadow located in the northeastern margin of the Qinghai-Tibet Plateau to study the changes of vegetation community and soil properties under different grazing intensities, as well as the quantitative relation between the distribution patterns of plant species and the physical and chemical properties of soil. The results showed that the grazing caused the differentiation of the initial vegetation community with the dominant plants, Elymus nutans and Stipa grandis. In the plots with high and low grazing intensities, the dominant plants had changed to Kobresia humilis and Melissitus ruthenica, and E. nutans and Poa crymophila, respectively. With the increase of grazing intensity, the plant richness, importance value and biomass were significantly decreased. The sequence of plant species importance value in each plot against grazing intensity could be fitted by a logarithmic model. The number of required plant species was reduced while the importance value of the remaining plant species accounted for 50% of the importance value in the whole vegetation community. The available P, available K, soil compaction, soil water content, stable infiltration rate and large aggregate index were significantly changed with grazing intensity, however, the changes were different. The CCA ordination showed that the soil compaction was the key factor affecting the distribution pattern of the plant species under grazing. The variance decomposition indicated that the soil factors together explained 30.5% of the distribution of the plant species, in particular the soil physical properties alone explained 22.8% of the distribution of the plant species, which had the highest rate of contribution to the plant species distribution. The soil physical properties affected the distribution pattern of plant species on grazed alpine meadow.

Objective: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in prophylaxis neutropenia after chemotherapy in patients with lymphoma. Methods: This was a multicenter, single arm, open, phase Ⅳ clinical trial. Included 410 patients with lymphoma received multiple cycles of chemotherapy and PEG-rhG-CSF was administrated as prophylactic. The primary endpoint was the incidence of Ⅲ/Ⅳ grade neutropenia and febrile neutropenia (FN) after each chemotherapy cycle. Meanwhile the rate of antibiotics application during the whole period of chemotherapy was observed. Results: ①Among the 410 patients, 8 cases (1.95%) were contrary to the selected criteria, 35 cases (8.54%) lost, 19 cases (4.63%) experienced adverse events, 12 cases (2.93%) were eligible for the termination criteria, 15 cases (3.66%) develpoed disease progression or recurrence, thus the rest 321 cases (78.29%) were into the Per Protocol Set. ②During the first to fourth treatment cycles, the incidences of grade Ⅳ neutropenia after prophylactic use of PEG-rhG-CSF were 19.14% (49/256) , 12.5% (32/256) , 12.18% (24/197) , 13.61% (20/147) , respectively. The incidences of FN were 3.52% (9/256) , 0.39% (1/256) , 2.54% (5/197) , 2.04% (3/147) , respectively. After secondary prophylactic use of PEG-rhG-CSF, the incidences of Ⅳ grade neutropenia decreased from 61.54% (40/65) in the screening cycle to 16.92% (11/65) , 18.46% (12/65) and 20.75% (11/53) in 1-3 cycles, respectively. The incidences of FN decreased from 16.92% (11/65) in the screening cycle to 1.54% (1/65) , 4.62% (3/65) , 3.77% (2/53) in 1-3 cycles, respectively. ③The proportion of patients who received antibiotic therapy during the whole period of chemotherapy was 34.39% (141/410) . ④The incidence of adverse events associated with PEG-rhG-CSF was 4.63% (19/410) . The most common adverse events were bone pain[3.90% (16/410) ], fatigue (0.49%) and fever (0.24%) . Conclusion: During the chemotherapy in patients with lymphoma, the prophylactic use of PEG-rhG-CSF could effectively reduce the incidences of grade Ⅲ/Ⅳ neutropenia and FN, which ensures that patients with lymphoma receive standard-dose chemotherapy to improve its cure rate.

The research selected the plots of six grazing intensities in an alpine meadow in north-eastern Tibet Plateau in four years (2012-2015) and studied the relation between ten species diversity indexes, including two measured indexes (Richness and Abundance) in field and two indexes of each dominance, evenness, richness, integrated indexes, and grazing intensity as well as grazing time aiming at scientific selection of biodiversity index under grazing disturbance. The results indicated that the abundance was a better index than importance value to calculate biodiversity level because it was more sensitive to grazing disturbance. Dominance indexes, including Berger-Parker and Dominance, were not sensitive to grazing intensity and grazing time because they could not clarify the effect of grazing disturbance on dominant species in plant community. Evenness indexes, including Equitability and Evenness, had not relation with grazing intensity, however, the evenness index had a negative correlation with grazing time and it was not influenced by occasional species as well as the variation coefficient of species abundance. Hereby, the evenness index could be chosen for studying evenness change at temporal scale. Richness indexes, including Menhinick and Margalef, had no relation with grazing time, however, the Margalef index had a positive correlation with grazing intensity and the index was not influenced by occasional species. Integrated index, including Shannon and Simpson indexes, had no relation with grazing intensity, however, the Shannon index had a significant positive correlation with species richness and abundance and the index was not influenced by occasional species, and it significantly increased along grazing time. Hereby, Shannon index could be used as an index of studying plant species diversity in long-term. In ten diversity indexes, only the measured indexes in field, including richness and abundance, were signifi-cantly negatively correlated with grazing intensity, and positively correlated with grazing time, and the two indexes were not influenced by occasional species. Hereby, the combination of species richness and abundance mea-sured in field could be considered as the most important indexes for studying plant species diversity under grazing disturbance. Besides, the selection of biodiversity indexes must consider the spatial-temporal feature of grazing, diversity components and research purpose.

For understanding the effect of aspect and altitude of hill on soil moisture and temperature as well as the vegetation community, we selected an alpine meadow located on a hill in north-eastern Tibet Plateau as our study area. Data on soil moisture and temperature, as well as plant distribution pattern in this mountain ecosystem were collected. We used regression analysis, CCA ordination and variance decomposition, to determine the impacts of the key factors (aspect, altitude, soil temperature and moisture) on plant diversity distribution in 189 sample sites of the hill. The results showed that the plant diversity of shady aspect and bottomland was highest and lowest, respectively. The plant diversity of the shady aspect and on the ridge of the hill increased initially and then decreased with the increasing altitude, but the plant diversity of the sunny aspect increased with the increasing altitude. At 0-30 cm soil layer, the soil temperature of the sunny aspect was higher than that of other aspects, but the soil temperature at 0-20 cm soil layer did not change with the increa-sing altitude. The soil moisture of shady aspect was higher than that of other aspects, and increased with the increasing altitude. The aspect and altitude explained 100% of soil temperature changes and 51.8% of soil moisture variation. Aspect alone explained 72.2% of soil temperature variation and altitude alone explained 51.8% of soil moisture variation, which had the highest contribution rate individually. Most plants were distributed on the shady aspect and on the ridge, and at medium altitude. Sedges mainly grew on the shady aspect, while Gramineae grew on the sunny aspect, the ridge was an ecotone. Cyperaceae, Gramineae and Leguminosae were mainly distributed in low altitude zone. Hill aspect and altitude totally explained 28.6% of plant abundance variation, hill aspect alone explained 19.9% of plant abundance variation. The management of grassland production and ecological restoration in alpine meadow ecosystem should consider the effect of landform on soil and vegetation, and the hill aspect should be priority factor instead of altitude when planning management interventions.

Probiotic treatment has been shown to improve bone formation, increase bone mass density and prevent bone loss. We aimed to assess the effect of probiotic treatment on functional recovery in elderly patients with a distal radius fracture. A total of 417 elderly patients with an acute distal radius fracture were enrolled in this double-blind placebo-controlled clinical trial. They were randomised to receive skimmed milk containing either a commercial probiotic (Lactobacillus casei Shirota) or placebo daily for a period of 6 months after the fracture. Treatment outcomes were the DASH (disabilities of the arm, shoulder and hand) score, pain, complex regional pain syndrome (CRPS) score, active range of motion and grip strength, all of which were measured on a monthly basis. Throughout the duration of the study, DASH score, pain, CRPS score, wrist flexion and grip strength of patients receiving probiotics exhibited a significantly faster pace of improvement than those on placebo, with treatment outcomes of patients receiving Lactobacillus casei Shirota at month 4 at comparable levels with those of patients receiving placebo at month 6. In elderly patients with a fracture of the distal radius, administration of the probiotic could greatly accelerating the healing process.

The Affordable Care Act (ACA) expanded Medicaid eligibility to adults with incomes under 138% of the federal poverty level, leading to substantial reductions in uninsured rates among low-income adults. Despite large gains in coverage, studies suggest that Latinos may be less likely than other racial/ethnic groups to apply and enroll in health insurance, and they remain the group with the highest uninsured rate in the United States. We explore two potential factors related to racial/ethnic differences in ACA enrollment-awareness of the law and receipt of application assistance such as navigator services. Using a survey of nearly 3000 low-income U.S. citizens (aged 19-64) in 3 states in late 2014, we find that Latinos had significantly lower levels of awareness of the ACA relative to other groups, even after adjusting for demographic covariates. Higher education was the strongest positive predictor of ACA awareness. In contrast, Latinos were much more likely to receive assistance from navigators or social workers when applying, relative to other racial/ethnic groups. Taken together, these results highlight the importance of ACA outreach efforts to increase awareness among low-income and less educated populations, two groups that are overrepresented in the Latino population, to close existing disparities in coverage., (© The Author(s) 2015.)

The aim of this study was to investigate the effects of miR-155 inhibitor transfection on the proliferation and apoptosis of THP-1 cells. The miR-155 inhibitor was transfected into THP-1 cells (THP-1I) by using X-treme GENE siRNA transfection reagent. Cells without transfection (THP-1C) and cells with negative transfection (THP-1IC) were used as controls. Quantitative real-time polymerase chain reaction (RT-PCR) was performed to detect the expression of miR-155 and relative expression of SHIP1 mRNA in the cells. Cell proliferation was assayed using CCK-8 method. Cell apoptosis were detected by flow cytometry. The expression of SHIP1, TAKT and pAKT in THP-1 cells were detected by Western blot. The results indicated that compared with THP-1C and THP-1IC, the expression of miR-155 in THP-1I cells was significantly reduced; miR-155 inhibition significantly increased apoptosis rate in THP-1 cells (P < 0.05) ; miR-155 inhibition in THP-1 cells caused no significant alteration in SHIP1 mRNA level but significantly increased its protein content, indicating some post-transcriptional modulations might exist underlying the modulation of miR-155 to SHIP1, the miR-155 caused significantly reduced protein level of pAKT (P < 0.05) without interfering TAKT protein content. It is concluded that the miR-155 inhibition may promote THP-1 cell apoptosis through increasing SHIP1 protein content and impairing its downstream PI3K/AKT signaling pathway. This study suggests that miR-155 inhibition may be a promising therapy strategy for treating acute myeloid leukemia (AML).

The SH2 domain-containing inositol 5'-phosphatase 1 (SHIP1) has been implicated as a suppressor of hematopoietic transformation as its activity can inhibit the PI3K/Akt signaling pathway. Reduced activity of SHIP1 has been observed in acute myeloid leukemia (AML). SHIP1 is a target of microRNA-155 (miR-155). Therefore, the aim of the present study was to investigate the role of miR-155/SHIP1 in the pathogenesis of AML. We examined the levels of SHIP1 protein and miR-155 in tissue samples of patients with AML and in AML cell lines. In addition, we investigated cell proliferation, apoptosis and expression of SHIP1/PI3K/AKT pathway molecules in the THP-1 and U937 cell lines after miR-155 inhibitor or mimics were transfected. We showed that the levels of SHIP1 protein were significantly decreased in tissue samples of patients with some subtypes of AML (M4 or M5) and in AML cell lines with concomitant overexpression of miR-155. In addition, we demonstrated that decreased expression of SHIP1 in the AML cell lines was a consequence of increased levels of miR-155 and can therefore be reversed in vitro through inhibition of miR-155, with subsequent inhibition of cell proliferation and promotion of cell apoptosis. In conclusion, expression of the SHIP1 protein is targeted by miR-155 in AML. miR-155 acts as an onco-miR, and the miR-155/SHIP1/PI3K/AKT signaling pathway could play an important role in the pathogenesis of AML.

The mammalian target of rapamycin (mTOR) pathway is essential for maintenance of the sensitivity of certain adult sensory neurons. Here, we investigated whether the mTOR cascade is involved in scorpion envenomation-induced pain hypersensitivity in rats. The results showed that intraplantar injection of a neurotoxin from Buthus martensii Karsch, BmK I (10 μg), induced the activation of mTOR, as well as its downstream molecules p70 ribosomal S6 protein kinase (p70 S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), in lumbar 5-6 dorsal root ganglia neurons on both sides in rats. The activation peaked at 2 h and recovered 1 day after injection. Compared with the control group, the ratios of p-mTOR/p-p70 S6K/p-4EBP1 in three types of neurons changed significantly. The cell typology of p-mTOR/p-p70 S6K/p-4E-BP1 immuno-reactive neurons also changed. Intrathecal administration of deforolimus, a specific inhibitor of mTOR, attenuated BmK I-induced pain responses (spontaneous flinching, paroxysmal pain-like behavior, and mechanical hypersensitivity). Together, these results imply that the mTOR signaling pathway is mobilized by and contributes to experimental scorpion sting-induced pain.

Intraplantar (i.pl.) injection of BmK I, a receptor site 3-specific modulator of voltage-gated sodium channels (VGSCs) from the venom of scorpion Buthus martensi Karsch (BmK), was shown to induce long-lasting and spontaneous nociceptive responses as demonstrated through experiments utilizing primary thermal and mirror-imaged mechanical hypersensitivity with different time course of development in rats. In this study, microglia was activated on both sides of L4-L5 spinal cord by i.pl. injection of BmK I. Meanwhile, the activation of p38/MAPK in L4-L5 spinal cord was found to be co-expressed with OX-42, the cell marker of microglia. The unilateral thermal and bilateral mechanical pain hypersensitivity of rat induced by BmK I was suppressed in a dose-dependent manner following pretreatment with SB203580 (a specific inhibitor of p-p38). Interestingly, microglia activity was also reduced in the presence of SB203580, which suggests that BmK I-induced microglial activation is mediated by p38/MAPK pathway. Combined with previously published literature, the results of this study demonstrate that p38-dependent microglial activation plays a role in scorpion envenomation-induced pain-related behaviors., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The mammalian target of rapamycin (mTOR) is known to regulate cell proliferation and growth by controlling protein translation. Recently, it has been shown that mTOR signaling pathway is involved in long-term synaptic plasticity. However, the role of mTOR under different pain conditions is less clear. In this study, the spatiotemporal activation of mTOR that contributes to pain-related behaviors was investigated using a novel animal inflammatory pain model induced by BmK I, a sodium channel-specific modulator purified from scorpion venom. In this study, intraplantar injections of BmK I were found to induce the activation of mTOR, p70 ribosomal S6 protein kinase (p70 S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) in rat L5-L6 spinal neurons. In the spinal cord, mTOR, p70 S6K and 4E-BP1 were observed to be activated in the ipsilateral and contralateral regions, peaking at 1-2 h and recovery at 24 h post-intraplantar (i.pl.) BmK I administration. In addition, intrathecal (i.t.) injection of rapamycin - a specific inhibitor of mTOR - was observed to result in the reduction of spontaneous pain responses and the attenuation of unilateral thermal and bilateral mechanical hypersensitivity elicited by BmK I. Thus, these results indicate that the mTOR signaling pathway is mobilized in the induction and maintenance of pain-activated hypersensitivity.

Vanillin is a food flavoring agent widely utilized in foods, beverages, drugs, and perfumes and has been demonstrated to exhibit multiple pharmacological activities. Given the importance of glucuronidation in the metabolism of vanillin, the UDP-glucuronosyltransferase conjugation pathway of vanillin was investigated in this study. Vanillin glucuronide was identified by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and a hydrolysis reaction catalyzed by β-glucuronidase. The kinetic study showed that vanillin glucuronidation by HLMs and HIMs followed Michaelis-Menten kinetics and the kinetic parameters were as follows: 134.9 ± 13.5 μM and 81.3 ± 11.3 μM for K(m) of HLMs and HIMs, 63.8 ± 2.0 nmol/min/mg pro and 13.4 ±2.0 nmol/min/mg pro for Vmax of HLMs and HIMs. All UDP-glucuronosyltransferase (UGT) isoforms except UGT1A4, 1A9, and 2B7 showed the capability to glucuronidate vanillin, and UGT1A6 exerted the higher V(max)/K(m) values than other UGT isoforms for the glucuronidation of vanillin when assuming expression of isoforms is similar in recombinant UGTs. Kinetic analysis using liver microsomes from six studied speices indicated that vanillin had highest affinity for the monkey liver microsomes enzyme (K(m)  = 25.6 ± 3.2 μM) and the lowest affinity for the mice liver microsomes enzyme (K(m)  = 149.1 ± 18.4 μM), and intrinsic clearance was in the following order: monkey > dog > minipig > mice > rat ~ human. These data collectively provided important information for understanding glucuronidation of vanillin., (Copyright © 2012 John Wiley & Sons, Ltd.)

MicroRNA (miRNA) are small non-coding RNA that act at the post-transcriptional level, regulating protein expression by repressing translation mRNA target. They can be detected in plants, animal species and viruses, and are involved in numerous cellular processes. MicroRNA-155 (miR-155) which is a kind of microRNAs expressed in hematopoietic cells. Recent data indicate that MiR-155 plays a key role in the pathogenesis of hematological malignancies through regulating cell signal transduction pathways of cell proliferation, differentiation and apoptosis, acting predominantly as an oncomir. MiR-155 may be an important indicator to assess the diagnosis, treatment and prognosis of patients with hematological malignancies, including malignant lymphoma, acute myeloid leukemia, and myelodysplastic syndrome. It could be suggested that drugs such as antisense oligonucleotides able to down-regulate miR-155 expression would provide a novel, and possibly specific way to control the growth of a range of haematopoietic malignancies in conjunction with classical cytotoxic therapy. The purpose of this review is to summarize current findings on the role of miR-155 in hematopoietic malignancies and, moreover, to highlight their role as potential therapeutic tools.

The integrated mechanisms of dynamic signaling of sodium channels involved in clinical pain are still not yet clear. In this study, a new rat inflammatory pain model was developed by using the unilateral intraplantar injection of BmK I, a receptor site 3-specific modulator of sodium channels from the venom of scorpion Buthus martensi Karsch (BmK). It was found that BmK I could induce several kinds of inflammatory pain-related behaviors including spontaneous pain companied with unique episodic paroxysms, primary thermal hypersensitivity, and mirror-image mechanical hypersensitivity with different time course of development, which could be suppressed by morphine, indomethacin, or bupivacaine to a different extent. The dramatic attenuation by pretreatment with resiniferatoxin (RTX), an ultrapotent analog of capsaicin, on BmK I-induced pain-related behaviors, paw edema, and spinal L4-L5 c-Fos expression demonstrated that capsaicin-sensitive primary afferent neurons played important roles in pain induced by BmK I. Furthermore, the electrophysiological recordings showed that BmK I persistently increased whole-cell and tetrodotoxin-resistant (TTX-R) peak sodium currents and significantly delayed the inactivation phase of whole-cell sodium currents but could not enhance capsaicin-evoked inward currents, in acute isolated small dorsal root ganglion neurons of rat. The results strongly suggested that the dynamic modulation of BmK I on sodium channels located in peripheral primary afferent neurons, especially in capsaicin-sensitive neurons, mediated pain sensation. Thus, BmK I may be a valuable pharmacological tool to understand the sodium channel-involved pain mechanisms., (Copyright © 2010 Elsevier Inc. All rights reserved.)