[Analysis of CHIP-Related Mutation and Risk of Cardio-Cerebrovasculars Events in Patients with Myeloproliferative Neoplasms].

OBJECTIVE: To analyze the mutant spectrum of clonal hematopoiesis of indeterminate potential (CHIP) related mutations and clinical characteristics and to explore the correlation and the possible mechanism between CHIP-related mutations and cardio-cerebrovasculars events (CCEs) in patients with myeloproliferative neoplasms (MPNs). METHODS: The clinical data and next-generation sequencing results of 73 MPN patients in Beijing Anzhen Hospital from August 2019 to July 2022 were retrospectively analyzed. Statistical analyses were conducted by multivariate logistic regression for the effects of CHIP-related mutations and inflammatory cytokines on CCEs for MPNs patients. RESULTS: Fifty-five cases of MPN (75.3%) showed positive in CHIP-related genes. There was no significant difference in variant allele frequency of CHIP-related gene between essential thrombocythemia (ET) and polycythemia vera (PV). CHIP-related gene mutations were mainly single gene mutations, with mutation rate from high to low as JAK2V617F (63.0%, 46/73), ASXL1 (16.4%, 12/73), TET2 (11.0%, 8/73), DNMT3A (9.6%, 7/73), SRSF2 (6.9%, 5/73), SF3B1 (4.1%, 3/73), TP53(1.4%, 1/73) and PPM1D (1.4%, 1/73). The mutation rate of CHIP-related genes in MPN patients >60 years old was significantly higher than that in the patients ≤60 years old ï¼»91.7%(33/36) vs 59.5%(22/37)ï¼½. CCEs occurred in 27 MPNs patients (37.0%, MPNs/CCEs), and 5 had recurrent CCEs, all of which were arterial events. Age (62.8±12.8 years vs 53.9±15.8 years, P =0.015), IL-1ß level (17.7±26.0 vs 4.3±8.6, P =0.012), IL-8 level (360.7±598.6 vs 108.3±317.0, P =0.045), the proportion of the patients with thrombosis history (29.6% vs 2.2%, P =0.020), and the detection rate of CHIP-related mutations (88.9% vs 67.4%, P =0.040) in the group with CCEs were higher than those in the group without CCEs. Multivariate Logistic regression analysis showed that age（OR =0.917， 95%CI ：0.843-0.999, P =0.047）, thrombosis history (OR =34.148， 95%CI ：2.392-487.535, P =0.009), any CHIP-related mutations(OR =16.065， 95%CI ：1.217-212.024， P =0.035), and elevated level of IL-1ß (OR =0.929， 95%CI ：0.870-0.992， P =0.027) were independent risk factors for MPNs/CCEs. CHIP-related gene mutations were not associated with CCEs in MPN patients, but DNMT3A (OR =88.717， 95%CI ：2.690-292.482， P =0.012) and ASXL1 (OR =7.941， 95%CI ：1.045-60.353， P =0.045) were independent risk factors for CCEs in PV. CONCLUSION: There is a higher mutation rate of CHIP-related genes in MPN patients, especially those over 60 years old. Older age, thrombosis history, CHIP-related mutations and IL-1ß elevated levels are independent risk factors for CCEs in MPN. DNMT3A and ASXL1 mutations are independent risk factors for CCEs in PV patients. CHIP-related gene mutations and inflammatory cytokine IL-1 ß elevated levels may be the novel risk factors for CCEs in MPN.

A convenient and practical index for predicting the induction response in adult patients with hemophagocytic lymphohistiocytosis: ferritin/platelet ratio.

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome with high mortality rate. The response to induction therapy is an important factor affecting survival. The purpose is to investigate laboratory predictors for induction response in adult patients with HLH, which are convenient, practical, and timeliness. Clinical data from January 2017 to December 2020 was retrospectively analyzed, and 269 patients were included. Patients were divided into remission and non-remission groups according to their induction response, 177 in the remission group, and 92 in the non-remission group. We reviewed general characteristics and analyzed the predictive value of serum ferritin, triglycerides, alanine aminotransferase (ALT), and blood cells before and 1-4 weeks after induction therapy for induction response by univariate analysis, ROC curves, etc. There was a correlation between serum ferritin, ALT, leukocytes, neutrophils, hemoglobin, platelets, and induction response (P < 0.05). Serum ferritin and platelets 1-4 weeks after induction therapy, respectively, might be a good predictor for induction response in adults with HLH, with AUC values close to or greater than 0.7. We established a new clinical model of the ferritin/platelet ratio. The results showed that the ferritin/platelet ratio at 1-4 weeks after induction therapy might be a practical index for predicting induction response, which significantly improved the area under the ROC curve (AUC > 0.75). Patients with a ferritin/platelet ratio > 16.08 at 2 weeks after induction therapy may have a relatively poor induction response. Ferritin/platelet ratio after induction therapy can be a good predictor for induction response in adult patients with HLH.

Sustainably developing global blue carbon for climate change mitigation and economic benefits through international cooperation.

Blue carbon is the carbon storage in vegetated coastal ecosystems such as mangroves, salt marshes, and seagrass. It is gaining global attention as its role in climate change mitigation and local welfare growth. However, a global assessment on the long-term spatiotemporal sustainable development status of blue carbon has not been conducted, and the relations among blue carbon ecosystems, driving forces for climate change mitigation, and socioeconomic interventions for development capacity on a global scale are still unclear. Here, we constructed a blue carbon development index (BCDI), comprising three subsystems: driving force, resource endowment, and development capacity, to assess the sustainable development level of 136 coastal countries' blue carbon over 24 consecutive years and explore the relationship among subsystems. We further propose a cooperation model to explore the feasibility of global blue carbon cooperation and quantify benefit allocation to specific countries. The results showed an upward trend in BCDI scores with variations in regional performance over the past two decades, and we found a positive correlation between development capacity and blue carbon resource endowment. Based on the scenario simulations of global cooperation, we found that coastal countries could improve the global average BCDI score, add 2.96 Mt of annual carbon sequestration, and generate $136.34 million in 2030 under Global Deep Cooperation scenario compared with the Business-As-Usual scenario.

The contribution of ocean-based solutions to carbon reduction in China.

Climate change has become a great challenge for humanity. However, the current climate change mitigation measures, primarily concentrate on land, more or less neglecting the vital role of the ocean-based solutions. While the ocean is a crucial regulator of the global climate, ocean-based solutions could also play an essential role in climate change mitigation and policymaking. This paper developed an Ocean-based Solutions Carbon Reduction Assessment Model (OSCRAM) that addresses coastal ecosystems, ocean energy, marine transportation, fishery, and seabed to estimate the oceanic contribution to climate change mitigation. It has been applied to evaluate the capacity of carbon emission reduction through oceans in China. We found that the total contribution for carbon emission reduction was about 6.86 Tg CO2 per year, and it may reach 139.39 Tg in 2030 under the target scenario. The results indicated that the ocean has huge potential to reduce carbon emissions. The development of marine energy and low-carbon marine shipping may have more potential for emission reduction in China, and the government should also protect and restore coastal wetlands for their enormous carbon storage. It can also provide a reference for the globe and other nations in achieving emission reduction goals.

The decade long achievements of China's marine ecological civilization construction (2006-2016).

China needs to balance between current population pressures and a vulnerable marine environment, creating a national, political outline or management strategy dubbed an ecological civilization construction. The nation's effort to protect and maintain a sustainable ocean and address the relevant economic, resource and environmental issues relies on Marine Ecological Civilization (MEC) construction. The quantification of MEC progress is essential to track the management performance and guide the subsequent development and implementation. This study evaluates the performance of China's MEC from 2006 to 2016 based on a comprehensive index system. Our findings are as follows: During 2006-2016, the overall MEC performance score increased from 0.3426 to 0.4850 nationwide. Large space-time variations exist among the eleven coastal regions. The Shandong and Guangdong regions showed relatively good performances, whereas the Jiangsu, Guangxi and Shanghai regions had low scores. A decade long change in MEC scores showed that Hebei achieved the largest increase ratio. Marine management was improved by implementing various conservation strategies by China's government. Marine education and human talent introduction deserve more attention in less developed areas such as Hainan and Guangxi, and poor marine environmental quality was an urgent issue of the Yangtze river estuary economic zone. More accessible marine monitoring dataset are needed to track future space-time progress dynamics towards MEC construction. Our results provide a decade long retrospect of China's MEC achievements, and the quantified evaluation for each coastal region can provide valuable insight to policy-makers.

Management of Postoperative Pain in Medical Institutions in Shandong Province in China.

The aim of the study was to investigate current situation of postoperative pain management in medical institutions in Shandong Province.A questionnaire was developed on the basis of guidelines of acute pain and pain quality assessment scale. The questionnaire was used to obtain information regarding the nature and scale of the medical institution, structure of pain management organization, implementation of pain assessment, and analgesic techniques and processes used in clinical practice. A multistage stratified and cluster sampling method was employed to investigate the current situation of postoperative pain management in 168 medical institutions in Shandong Province.For acute pain service (APS), 32% of the hospitals established postoperative pain management organizations similar to APS. For pain evaluation, 57.1% of the hospitals evaluated pain as the fifth vital sign, and 47.0% of the hospitals evaluated pain at rest and during activity. Furthermore, 43.0% of the surveyed hospitals employed patient-controlled analgesia mode, of which hospitals employing brachial plexus block, lumbar plexus block, and femoral nerve block analgesia accounted for 5.0%, 1.0%, and 4.0%, respectively. The survey revealed that 51.0% of the hospitals educated patients about pain and pain management, of which patients were postoperatively educated by ward nurses in 5.0% and patients were educated by APS during ward rounds in 2.0%.There is a lack of standardized postoperative pain management, the involvement of nurses in pain management is scarce, and the pain assessment and education and application of advanced analgesic management techniques were found to be inadequate in medical institutions in Shandong Province.

Overexpression of the receptor-like protein kinase genes AtRPK1 and OsRPK1 reduces the salt tolerance of Arabidopsis thaliana.

AtRPK1 (AT1G69270) is a leucine-rich repeat receptor-like protein kinase (LRR-RLK) gene in Arabidopsis thaliana. The rice gene Os07g0602700 (OsRPK1) is the homolog of AtRPK1. AtRPK1 and OsRPK1 were overexpressed and the expression of AtRPK1 was inhibited by RNAi in A. thaliana. The functional results showed that the degrees of salt tolerance of the 35S:RPK1 A. thaliana plants were significantly lower than that of the control plants. The AtRPK1-RNAi A. thaliana plants exhibited higher salt tolerance than the wild-type plants (Col). The subcellular localisation results showed that the RPK1 proteins were mainly distributed on the cell membrane and that the overexpressed AtRPK1 proteins exhibited a significantly clustered distribution. The physiological analyses revealed that the overexpression of the RPK1 genes increased the membrane permeability in the transgenic A. thaliana plants. In response to salt stress, these plants exhibited an increased Na(+) flux into the cell, which caused greater damage to the cell. The real-time quantitative PCR analysis showed that the expression of the P5CS1 gene was inhibited and the SOS signalling pathway was blocked in the 35S:AtRPK1 A. thaliana plants. These effects at least partially contribute to the salt-sensitive phenotype of the 35S:RPK1 plants.

[Etiology analysis of 38 patients with hemophagocytic syndrome].

The study was aimed to investigate the etiology and the clinical characteristics of patients with hemophagocytic syndrome. The clinical data of 38 patients with hemophagocytic syndrome were retrospectively analyzed, and prf1 and stx11 were detected for the mutational analysis. The results showed that 38 cases were diagnosed as hemophagocytic syndrome, including 1 case of familial hemophagocytic lymphohistiocytosis (FHL), 14 cases associated with infectious disease (36.84%), 10 cases with malignancies (26.32%), 7 cases with rheumatic disease (18.42%), other 6 cases of unknown etiology (15.79%). 9 out of 38 cases died with mortality of 23.68%, including 4 cases associated with infectious disease, 2 cases with malignancies, 1 case with rheumatic disease, and 2 cases of unknown etiology. One case was found to have prf1 mutation, and was diagnosed as FHL at last. It is concluded that the causes of HPS are diverse, different etiology results in different outcome. It is important to find etiology when HPS is diagnosed, and prf1 and stx11 genetic analysis plays a important role in the diagnosis of FHL.

Early diagnostic value of low percentage of glycosylated ferritin in secondary hemophagocytic lymphohistiocytosis.

Elevated levels of serum ferritin and a low percentage of glycosylated ferritin have been reported in adult-onset Still's disease (AOSD) as well as in hemophagocytic lymphohistiocytosis (HLH). The objective of the current study was to investigate total ferritin levels and the percentage of glycosylated ferritin in patients with secondary HLH. From October 2007 to October 2008, 29 patients with suspected HLH older than 14 years of age treated at Beijing Friendship Hospital were enrolled. Twenty-five healthy volunteers were recruited as controls. The suspected HLH patients were further divided into secondary HLH-confirmed (confirmed) (22 out of 29) and HLH-unconfirmed (unconfirmed) (7 out of 29) groups based on HLH-2004 diagnostic criteria. Total serum ferritin levels and the percentage of glycosylated ferritin were determined in subjects at the time of admission. Significantly higher levels of total serum ferritin were observed in confirmed (2,897.6 +/- 1,837.2 microg/L) compared with unconfirmed (653.1 +/- 249.1 microg/L) patients (P < 0.01) or controls (414.6 +/- 212.6 microg/L) (P < 0.01). A significantly lower percentage of glycosylated ferritin was observed in the confirmed (20.5 +/- 10.1%) compared with the unconfirmed (48.7 +/- 12.1%) group (P < 0.01) or the control group (53.6 +/- 13.3%) (P < 0.01). In addition, a low percentage of glycosylated ferritin was observed in HLH patients. Finally, regarding the diagnosis of HLH based on a low percentage of glycosylated ferritin, the sensitivity and specificity, as well as positive and negative predictive values were 0.86, 0.71, 0.91, and 0.63, respectively. For the diagnosis of HLH based on hyperferritinemia, the sensitivity, specificity, positive, and negative predictive values were 0.82, 0.43, 0.82, and 0.43, respectively. The results of this study suggest that a low percentage of glycosylated ferritin is associated with HLH. On comparison with hyperferritinemia, a low percentage of glycosylated ferritin appeared to be more specific, sensitive, and predictive of HLH. In conclusion, a low percentage of glycosylated ferritin may be a useful marker for the early diagnosis of secondary HLH.

[The early diagnosis and clinical analysis of 57 cases of acquired hemophagocytic lymphohistiocytosis].

OBJECTIVE: To explore the significance of NK cell activity, interleukin-2 receptors (sCD(25)) and glycosylated ferritin in the early diagnostic of acquired hemophagocytic lymphohistiocytosis (HLH). METHODS: 57 patients suspected of HLH from June 2005 to May 2008 and 25 healthy subjects were enrolled in the study. The patients suspected of HLH were divided into three groups i.e. (1) a group with diagnosis confirmed at first visit; (2) a group with diagnosis confirmed at subsequent visit and (3) a group with diagnosis unconfirmed according to HLH-2004 diagnostic criteria. Healthy subjects were enrolled as control. NK cell activity was determined with a released LDH assay. The percentage of glycosylated ferritin was determined with phytohemagglutinin adsorption assay. sCD(25) was examined with ELISA double antibody sandwich assay. We compared the coincidence of each diagnostic index before and after diagnosis. RESULTS: The median percentage of NK cell activity was significantly lower in the first group (18.3 +/- 5.6)% and the second (16.7 +/- 6.7)% than that in the third group (33.4 +/- 6.8)% or in the controls (36.6 +/- 5.0)%. The median percentage of glycosylated ferritin was also significantly lower in the first group (15.4 +/- 2.0)% and the second group (16.9 +/- 3.4)% than that in the third group (40.4 +/- 3.0)% or in the controls (45.2 +/- 2.2)%. Meanwhile, the median level of sCD(25) was significantly higher in the first group (12 916 +/- 4328) ng/L and the second group (12 117 +/- 5465) ng/L than that in the third group (4728 +/- 1482) ng/L or in the controls (3841 +/- 993) ng/L. Furthermore, NK cell activity, sCD(25) and glycosylated ferritin were abnormal in all the patients in the early stage of HLH. CONCLUSION: NK cell activity, sCD(25) and glycosylated ferritin may be helpful markers for the early diagnosis of HLH.

[Diagnostic significance of glycosylated ferritin for patients with secondary hemophagocytic lymphohistiocytosis].

This study was aimed to explore the level of glycosylated ferritin in the patients with secondary hemophagocytic lymphohistiocytosis (HLH) and its diagnostic significance. 29 suspected HLH patients from October 2007 to October 2008 were enrolled in the study, and 25 healthy subjects were selected as control. The 29 suspected HLH patients were divided into confirmed group (22 out of 29) and unconfirmed group (7 out of 29) according to HLH-2004 diagnostic criteria. The percentage of glycosylated ferritin in peripheral blood was determined by phytohemagglutinin adsorption assay. The results showed that the median level of total serum ferritin in patients of confirmed group (2897.6+/-1837.2 microg/L) was significantly higher than that in patients of unconfirmed group (653.1+/-249.1 microg/L) (p<0.01), and was also higher than that in controls (414.6+/-212.6 microg/L) (p<0.01). The median percentage of glycosylated ferritin in patients of confirmed group was significantly lower (17.0+/-4.2%) than that in patients of unconfirmed group (40.7+/-4.5%) (p<0.01) and was lower than that in controls (53.6+/-13.3%) (p<0.01). The sensitivity (86.4% vs 77.3%) and specificity (71.4% vs 42.9%) of glycosylated ferritin for the diagnosis of HLH were higher than that of total serum ferritin. In conclusions, glycosylated ferritin may be a helpful marker for the diagnosis of HLH.

[Diagnostic significance of NK cell activity in the patients with hemophagocytic syndrome].

This study was aimed to explore the level of NK cell activity in the patients with secondary hemophagocytic syndrome (HPS) and its significance for early diagnosis of this disease. 16 suspected HPS patients and 25 healthy subjects were enrolled in this study. The activity of NK cells in peripheral blood was detected by a released LDH assay. The activity level of NK cells in peripheral blood from patients who were finally diagnosed as HPS was compared with healthy subjects. The results showed that 8 out of 16 suspected HPS patients were finally diagnosed as secondary HPS. The activity of NK cells in peripheral blood of these 8 patients was obviously lower than that in healthy subjects with statistical significance (p<0.001), and showed abnormal in the early stage of this disease. It is concluded that the detection of NK cell activity may play an important role in earlier diagnosis of secondary hemophagocytic syndrome.

[Transforming growth factor beta alleviates acute graft-versus-host-disease after allogeneic bone marrow transplantation in murine model].

This study was purposed to investigate the effects and mechanism of transforming growth factor beta (TGF-beta) on acute graft-versus-host disease (aGVHD) after allogeneic bone marrow transplantation (allo-BMT). The recipients were male BABL/c mice, while the donors were male C57BL/6 mice. The murine model of aGVHD had been established by allo-BMT with donor derived T cells. Experiment was divided into four groups: control group, radiation control group, transplantation control group and TGF-beta treated group. Mice in TGF-beta treated group were daily subcutaneously injected TGF-beta1 (1 microg/kg) in two days before transplantation until seven days after it. The results showed that the survival time of mice in TGF-beta treated group was significantly longer than that in transplantation control group, and the aGVHD pathological changes in TGF-beta treated group were milder than that in transplantation control group. At seven days after transplantation, the level of IL-2 in TGF-beta treated group was significantly higher than that in control group, but significantly lower than that in transplantation control group. The level of IL-10 in TGF-beta treated group was significantly higher than that in transplantation control group, but the level of IL-10 in transplantation control group was significantly lower than that in other groups. It is concluded that TGF-beta may alleviate or suppress lethal aGVHD, and elevate the survival rate after allo-BMT in murine model. Accommodating of the Th1 and Th2 cytokine levels is the possible mechanism of TGF-beta preventing lethal aGVHD.

[Diagnostic significance of NK cell activity and soluble CD25 level in serum from patients with secondary hemophagocytic lymphohistiocytosis].

This study was aimed to explore the clinical significance of NK cell activity and serum soluble CD25 (sCD25) level in early diagnosis of the patients with secondary hemophagocytic lymphohistiocytosis (HLH). 38 suspected secondary HLH patients from June 2005 to June 2008 and 25 healthy subjects were enrolled in the study. The NK cell activity in peripheral blood was determined by a released LDH assay, The sCD25 level in serum was detected with ELISA double antibody sandwich assay. The 38 suspected secondary HLH patients were divided into diagnosed and excluded group according to HLH-2004 diagnostic criteria, The NK cell activity and sCD25 level were compared between the two groups. The results showed that 22 out of 38 suspected patients were diagnosed as secondary HLH, the NK cell activity in peripheral blood of these 22 patients was significantly lower than that of healthy control (p < 0.001), the sCD25 level in peripheral blood of these 22 diagnosed patients was higher than that of healthy control (p < 0.05). In conclusion, detection of NK cell activity and sCD25 level may be valuable in the early diagnosis of secondary HLH.