Burden of drug use disorders in the United States from 1990 to 2021 and its projection until 2035: results from the GBD study.

BACKGROUND: Drug use disorders (DUDs) have emerged as one of the most significant public health crises, exerting a substantial influence on both community health and socio-economic progress. The United States (US) also suffers a heavy burden, it is necessary to figure out the situation from multiple perspectives and take effective measures to deal with it. Therefore, using the data from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2021, we evaluated this topic. METHODS: Annual data on DUDs-related burden were collected from the GBD study 2021. We calculated the indicator of estimated annual percentage change (EAPC) to evaluate the changing trend of burden. The Bayesian model for age-period-cohort was introduced to forecast the burden. RESULTS: In 2021, the number and age-standardized rate of prevalence were particularly prominent, with 12,146.95 thousand and 3821.43 per 100,000, respectively. Higher burden was also observed in males, 15-45 years old populations, and opioid use disorders subtype. From 1990 to 2021, the DUDs-related burden increased in the US and all states, especially in West Virginia; and the national death-related burden with the highest increase (EAPC = 7.96). Other significant inverse associations were seen between EAPC, age-standardized rates, and socio-demographic index (SDI). Moreover, in the next 14 years, the projected DUDs burden remains exigent. CONCLUSIONS: The burden of DUDs in the US is heavy and has been enlarging. This study proposes that greater attention should be paid to the strategies in males, the younger population, opioid use disorders, and low-SDI states implemented by decision-makers to achieve goals such as reducing burden.

Transfusion burden and willingness to pay for temporary alleviation of anemia status in transfusion-dependent beta-thalassemia patients in China.

BACKGROUND: Transfusion-dependent ß-thalassemia (TDT) is one of the global public health concerns highlighted by the World Health Organization. Patients with TDT require regular blood transfusion to survive. However, the availability of blood resources is extremely limited. The purpose of this study was to investigate transfusion burden and willingness to pay (WTP) for temporary remission of anemia status among patients with TDT and to explore the associated factors. METHODS: Adult patients with TDT were recruited through cluster sampling across several high-incidence provinces in China. Consenting patients completed online questionnaires on demographic information, transfusion burden and WTP with real-time WeChat communication assistance from researchers. The guiding techniques of double-bounded dichotomous choices and open-ended questions in the contingent valuation method (CVM) were used to obtain participants' WTP for 1 unit of leukocyte-depleted red blood cells. WTP calculations were performed using maximum likelihood estimation, with further insights gained through subgroup analysis based on gender, family monthly income level and convenience of blood transfusion. RESULTS: The analysis included 149 TDT patients from five high-incidence provinces, with an average monthly income of $198.5. Patients received an average of 3.7 units per transfusion, 15.4 times annually, with an average WTP of $70.4 per unit (95% CI [62.0, 78.9]). Estimated WTP for temporary anemia alleviation per transfusion totaled $260.6, exceeding monthly income by 1.32 times. Higher WTP was observed among males, higher-income households, and those with at least junior education. Lower WTP was noted among patients with lower transfusion volumes and those needing to travel for transfusion or during hospitalization for blood transfusion. CONCLUSION: High WTP indicated a strong desire for temporary anemia relief. Most TDT patients faced significant economic and transfusion burden. The evident gap in meeting clinical needed underscores the urgent demand for innovative treatments to reduce transfusion dependency, potentially transforming TDT care and improving socioeconomic well-being and clinical outcomes. These findings supported evidence-based decision-making for TDT pharmacoeconomics and efficient healthcare resource allocation in China.

Marker-Assisted Selection of Jacalin-Related Lectin Genes OsJRL45 and OsJRL40 Derived from Sea Rice 86 Enhances Salt Tolerance in Rice.

Soil salinization limits rice growth and is an important restriction on grain yield. Jacalin-related lectins are involved in multiple stress responses, but their role in salt stress responses and use as molecular markers for salt tolerance remain poorly understood. Salt stress treatments and RT-qPCR analyses of Sea Rice 86 (SR86), 9311, and Nipponbare (Nip) showed that OsJRL45 and OsJRL40 enhanced tolerance of salt stress in SR86. Molecular markers based on sequence differences in SR86 and the salt-sensitive variety, 9311, in the intergenic region between OsJRL45 and OsJRL40 were validated in recombinant inbred lines derived from SR86 and 9311, hybrid populations, and common rice varieties. Yeast two-hybrid and bimolecular fluorescence complementation demonstrated that OsJRL45 and OsJRL40 interacted. Co-transformation of Nip with OsJRL45 and OsJRL40 derived from SR86 had no effect on the mature phenotype in T2 plants; however, salt stress at the three-leaf stage led to significant increases in CAT, POD, SOD, and Pro contents, but reduced MDA content in transgenic plants. Transcriptomic analysis identified 834 differentially expressed genes in transgenic plants under salt stress. GO and KEGG enrichment analyses indicated that metabolic pathways related to antioxidant responses and osmotic balance were crucial for salt-stress tolerance. Thus, molecular markers based on nucleotide differences in OsJRL45 and OsJRL40 provide a novel method for identifying salt-tolerant rice varieties.

Reconstruction for extensive sacrococcygeal defects in complex tumor patients with personalized customized gluteus maximus myocutaneous flaps.

AIM: To evaluate the clinical effects of personalized customized gluteus maximus myocutaneous flaps (GMMF) for reconstruction of extensive sacrococcygeal soft tissue defects in complex tumor patients. METHODS: A retrospective chart review was conducted on 8 patients who underwent personalized customized GMMF reconstruction for large sacrococcygeal defect from December 2021 to August 2023. The personalized customized GMMF were designed based on the variations of tissue defect in location, shape and volume of different dead spaces. The principle of the personalized GMMF is to ensure that the rotation point of the flap can reach the farthest end of the defect. Patient demographics, operative characteristics, and perioperative risk factors were analyzed. Clinical outcomes were assessed, focusing on complications such as flap necrosis, wound dehiscence, infection, seroma, and hematoma. RESULTS: Six patients with rectal cancer and two with sacral tumors underwent personalized customized GMMF reconstruction for extensive sacrococcygeal defects. The average volume of the wound cavity was 104 mL, with a mean vertical depth was 10.8 cm. Six patients had low serum albumin (<35 g/L). After a mean follow-up of 15.5 months, no major complications occurred, except for one seroma that resolved within 2 weeks. CONCLUSION: The personalized customized GMMF described in this study is an effective method for reconstructing large sacrococcygeal wounds with significant depth in complex tumor patients. It allows for greater rotation of the muscle flap into the sacrococcygeal wound defect and provides adequate blood supply by utilizing the bulk of muscle tissue to obliterate dead space.

Surgical treatment of unilateral acquired superior oblique muscle palsy in adults by inferior oblique belly transposition: a retrospective analysis.

PURPOSE: Evaluate and analyze the efficacy of inferior oblique belly transposition (IOBT) in treating adult patients with diplopia and small-angle hypertropia caused by mild to moderate inferior oblique overaction (IOOA) secondary to acquired superior oblique palsy (SOP). METHODS: Nine adult patients with diplopia and small-angle hypertropia associated with mild to moderate IOOA secondary to unilateral acquired SOP were included in the current retrospective study. All patients received the IOBT procedure between February 2019 and May 2023 at The Second People's Hospital of Jinan and were followed up for more than 6 months after the surgery. During the procedure, the belly of the inferior oblique muscle was fixed to the sclera at 5 mm posterior to the temporal insertion of the inferior rectus muscle. The following indicators were reviewed pre- and post-surgery: the vertical deviation (VD) in the primary position and in the Bielschowsky test, the fovea disc angle (FDA) of the affected eye, changes in IOOA, and diplopia. RESULTS: After IOBT, the VD in the primary position decreased from 7.22△ ± 1.72△ (range 4△-10△) to 1.22△ ± 1.30△ (range 0△-3△). The VD in the Bielschowsky test decreased from 13.00△ ± 1.80△ to 3.22△ ± 1.09△. The FDA decreased from 10.02° ± 3.34° to 6.26° ± 1.91°. The grade of IOOA was reduced from 2.00 (1.00, 2.00) to 0.00 (0.00, 1.00). All changes were statistically significant (P < 0.001 or P = 0.006). Diplopia was resolved completely for all patients. CONCLUSIONS: IOBT can effectively treat adults with diplopia and small-angle hypertropia caused by mild to moderate IOOA secondary to acquired SOP.

Jacalin-related lectin 45 (OsJRL45) isolated from 'sea rice 86' enhances rice salt tolerance at the seedling and reproductive stages.

BACKGROUND: Rice (Oryza sativa L.) is one of the most widely cultivated grain crops in the world that meets the caloric needs of more than half the world's population. Salt stress seriously affects rice production and threatens food security. Therefore, mining salt tolerance genes in salt-tolerant germplasm and elucidating their molecular mechanisms in rice are necessary for the breeding of salt tolerant cultivars. RESULTS: In this study, a salt stress-responsive jacalin-related lectin (JRL) family gene, OsJRL45, was identified in the salt-tolerant rice variety 'sea rice 86' (SR86). OsJRL45 showed high expression level in leaves, and the corresponding protein mainly localized to the endoplasmic reticulum. The knockout mutant and overexpression lines of OsJRL45 revealed that OsJRL45 positively regulates the salt tolerance of rice plants at all growth stages. Compared with the wild type (WT), the OsJRL45 overexpression lines showed greater salt tolerance at the reproductive stage, and significantly higher seed setting rate and 1,000-grain weight. Moreover, OsJRL45 expression significantly improved the salt-resistant ability and yield of a salt-sensitive indica cultivar, L6-23. Furthermore, OsJRL45 enhanced the antioxidant capacity of rice plants and facilitated the maintenance of Na+-K+ homeostasis under salt stress conditions. Five proteins associated with OsJRL45 were screened by transcriptome and interaction network analysis, of which one, the transmembrane transporter Os10g0210500 affects the salt tolerance of rice by regulating ion transport-, salt stress-, and hormone-responsive proteins. CONCLUSIONS: The OsJRL45 gene isolated from SR86 positively regulated the salt tolerance of rice plants at all growth stages, and significantly increased the yield of salt-sensitive rice cultivar under NaCl treatment. OsJRL45 increased the activity of antioxidant enzyme of rice and regulated Na+/K+ dynamic equilibrium under salinity conditions. Our data suggest that OsJRL45 may improve the salt tolerance of rice by mediating the expression of ion transport-, salt stress response-, and hormone response-related genes.

Effects of air pollution control policies on intracerebral hemorrhage mortality among residents in Tianjin, China.

BACKGROUND: Exposure to air pollution is an important risk factor for intracerebral hemorrhage (ICH), which is a major cause of death worldwide. However, the relationship between ICH mortality and air quality improvement has been poorly studied. This study aims to evaluate the impact of the air pollution control policies in the Beijing-Tianjin-Hebei region on ICH mortality among Tianjin residents. METHODS: This study used an interrupted time series analysis. We fitted autoregressive integrated moving average (ARIMA) models to assess the changes in ICH deaths before and after the interventions of air pollution control policies based on the data of ICH deaths in Tianjin collected by the Tianjin Center for Disease Control and Prevention. RESULTS: Between 2009 and 2020, there were 63,944 ICH deaths in Tianjin, and there was an overall decreasing trend in ICH mortality. The intervention conducted in June 2014 resulted in a statistically significant (p = 0.03) long-term trend change, reducing the number of deaths from ICH by 0.69 (95% confidence interval [CI]: -1.30 to -0.07) per month. The intervention in October 2017 resulted in a statistically significant (p = 0.04) immediate decrease of 25.74 (95% CI: -50.62 to -0.85) deaths from ICH in that month. The intervention in December 2017 caused a statistically significant (p = 0.04) immediate reduction of 26.58 (95% CI: -52.02 to -1.14) deaths from ICH in that month. The intervention in March 2018 resulted in a statistically significant (p = 0.02) immediate decrease of 30.40 (95% CI: -56.41 to -4.40) deaths from ICH in that month. No significant differences were observed in the changes of male ICH mortality after any of the four interventions. However, female ICH deaths showed statistically significant long-term trend change after the intervention in June 2014 and immediate changes after the interventions in December 2017 and March 2018. Overall, the interventions prevented an estimated 5984.76 deaths due to ICH. CONCLUSION: During the study period, some interventions of air pollution control policies were significantly associated with the reductions in the number of deaths from ICH among residents in Tianjin. ICH survivors and females were more sensitive to the protective effects of the interventions. Interventions for air pollution control can achieve public health gains in cities with high levels of air pollution.

OsJRL40, a Jacalin-Related Lectin Gene, Promotes Salt Stress Tolerance in Rice.

High salinity is a major stress factor affecting the quality and productivity of rice (Oryza sativa L.). Although numerous salt tolerance-related genes have been identified in rice, their molecular mechanisms remain unknown. Here, we report that OsJRL40, a jacalin-related lectin gene, confers remarkable salt tolerance in rice. The loss of function of OsJRL40 increased sensitivity to salt stress in rice, whereas its overexpression enhanced salt tolerance at the seedling stage and during reproductive growth. ß-glucuronidase (GUS) reporter assays indicated that OsJRL40 is expressed to higher levels in roots and internodes than in other tissues, and subcellular localization analysis revealed that the OsJRL40 protein localizes to the cytoplasm. Further molecular analyses showed that OsJRL40 enhances antioxidant enzyme activities and regulates Na+-K+ homeostasis under salt stress. RNA-seq analysis revealed that OsJRL40 regulates salt tolerance in rice by controlling the expression of genes encoding Na+/K+ transporters, salt-responsive transcription factors, and other salt response-related proteins. Overall, this study provides a scientific basis for an in-depth investigation of the salt tolerance mechanism in rice and could guide the breeding of salt-tolerant rice cultivars.

Burden of pancreatic cancer along with attributable risk factors in China from 1990 to 2019, and projections until 2030.

OBJECTIVES: Understanding epidemiology trends and patterns of pancreatic cancer in China from 1990 to 2019 and predicting the burden to 2030 will provide foundations for future policies development. METHODS: We collected incidence, mortality, and disability-adjusted life-years (DALYs) data of pancreatic cancer in China from 1990 to 2019 based on the Global Burden of Disease Study 2019. We calculated the estimated annual percentage change (EAPC) to depict the trends of pancreatic cancer burden and predicted the incidence and mortality in the next decade by using a Bayesian age-period-cohort analysis. RESULTS: The number of incident cases sharply increased from 26.77 thousand in 1990 to 114.96 thousand in 2019, the age-standardized incidence rate (ASIR) nearly doubled from 3.17 per 100,000 in 1990 to 5.78 per 100,000 in 2019, with an EAPC of 2.32 (95% confidence interval [CI]: 2.12, 2.51). The mortality and DALYs presented a similar pattern with incidence. The dominant risk factor for pancreatic cancer was smoking, but the contribution of high body-mass index increased from 1990 to 2019. We projected that the incident cases and deaths of pancreatic cancer would increase to 218.79 thousand and 222.97 thousand, respectively, in 2030 with around 2 times growth. CONCLUSIONS: During the past three decades, the incidence, mortality and DALYs of pancreatic cancer gradually increased in China, and the absolute number and rate of pancreatic cancer burden would continue to rise over the next decade. Comprehensive policies and strategies need to be implemented to reduce the incidence and mortality.

The global, regional, and national disease burden of breast cancer attributable to low physical activity from 1990 to 2019: an analysis of the Global Burden of Disease Study 2019.

BACKGROUND: To assess the spatiotemporal variation in female breast cancer attributable to low physical activity (LPA) at a global scale from 1990 to 2019, which is essential to promote physical activity, as well as prevent and control breast cancer. METHODS: The number of deaths and disability-adjusted life years (DALYs), and the corresponding age-standardized rates (ASMR and ASDR) of LPA-related breast cancer in 204 countries and territories from 1990 to 2019 were retrieved from the Global Burden of Disease Study 2019 to measure the related breast cancer burden by age and region. The estimated annual percentage change (EAPC) was calculated to quantify the secular trend in breast cancer burden rates. RESULTS: From 1990 to 2019, globally, both breast cancer deaths and DALYs attributable to LPA nearly doubled, although the corresponding ASMR and ASDR decreased slightly, with EAPC of -0.46 (95% confidence interval: -0.52, -0.40) and -0.44 (95% confidence interval: -0.49, -0.39), respectively. The LPA-related breast cancer burden varied considerably across the world, with the highest-burden rates in Oceania, Tropical Latin America and Caribbean, and the fastest growth in North Africa and Middle East. The ASMR and ASDR showed a logarithmic association with the Socio-demographic Index, and a temporally upward trend in most of 204 countries regardless of the Socio-demographic Index or the ASMR in 1990. CONCLUSIONS: Despite a decline in LPA-related breast cancer burden achieved in many countries during the last 3 decades like Bermuda, Myanmar, USA and China, an increase still occurred in most of 204 countries and territories, such as Solomon Islands, Equatorial Guinea, Japan and India. The findings can bring greater awareness to the importance of promoting physical activity for the local government to control the attributable breast cancer burden.

Novel MLL/KMT2A-MON2 fusion in a child with therapy-related acute myeloid leukemia after treatment for acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML), which is characterized by the reciprocal t (15;17) (q24; q21) translocation, resulting in PML-RARA gene fusion. Therapy-related AML (t-AML) is a serious complication after cytotoxic and/or radiation therapy in many malignant diseases. In this report, MLL/KMT2A-MON2, with balanced chromosomal translocation t (11;12) (q23; q14), was identified as a novel fusion in a child transformed to t-AML after successful treatment of APL. This study emphasized that clinical monitoring with an integrated laboratory approach is essential for the diagnosis and treatment of t-AML.

A nomogram for screening esophageal squamous cell carcinoma based on environmental risk factors in a high-incidence area of China: a population-based case-control study.

BACKGROUND: Selection of high-risk subjects for endoscopic screening of esophageal squamous cell carcinoma (ESCC) lacks individual predictive tools based on environmental risk factors. METHODS: We performed a large population-based case-control study of 1418 ESCC cases and 1992 controls in a high-risk area of China. Information on potential risk factors was collected via face-to-face interview using an electronic structured questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models, and predictive nomograms were established accordingly. A weighted analysis was further conducted to introduce age into predictive nomograms due to frequency matching study design. RESULTS: Most cases were usually exposed to 4 to 6 risk factors, but most controls were usually exposed to 3 to 5 risk factors. The AUCs of male and female predictive nomograms were 0.75 (95%CI: 0.72, 0.77) and 0.76 (95%CI: 0.73, 0.79), respectively. The weighted analysis adding age in the predictive model improved the AUC in both men and women (0.81 (95%CI: 0.79, 0.84) and 0.88 (95%CI: 0.85, 0.90), respectively). CONCLUSIONS: An easy-to-use preclinical predictive tool is provided to select candidate population with high ESCC risk for endoscopic screening. Its usefulness needs to be further evaluated in future screening practice.

Changing trends of disease burden of gastric cancer in China from 1990 to 2019 and its predictions: Findings from Global Burden of Disease Study.

OBJECTIVE: China is one of the countries with the heaviest burden of gastric cancer (GC) in the world. Understanding the epidemiological trends and patterns of GC in China can contribute to formulating effective prevention strategies. METHODS: The data on incidence, mortality, and disability-adjusted life-years (DALYs) of GC in China from 1990 to 2019 were obtained from the Global Burden of Disease Study (2019). The estimated annual percentage change (EAPC) was calculated to evaluate the temporal trends of disease burden of GC, and the package Nordpred in the R program was used to perform an age-period-cohort analysis to predict the numbers and rates of incidence and mortality in the next 25 years. RESULTS: The number of incident cases of GC increased from 317.34 thousand in 1990 to 612.82 thousand in 2019, while the age-standardized incidence rate (ASIR) of GC decreased from 37.56 per 100,000 in 1990 to 30.64 per 100,000 in 2019, with an EAPC of -0.41 [95% confidence interval (95% CI): -0.77, -0.06]. Pronounced temporal trends in mortality and DALYs of GC were observed. In the next 25 years, the numbers of new GC cases and deaths are expected to increase to 738.79 thousand and 454.80 thousand, respectively, while the rates of incidence and deaths should steadily decrease. The deaths and DALYs attributable to smoking were different for males and females. CONCLUSIONS: In China, despite the fact that the rates of GC have decreased during the past three decades, the numbers of new GC cases and deaths increased, and will continue to increase in the next 25 years. Additional strategies are needed to reduce the burden of GC, such as screening and early detection, novel treatments, and the prevention of risk factors.

The association of HBG2, BCL11A, and HBS1L-MYB polymorphisms to thalidomide response in Chinese ß-thalassemia patients.

Thalidomide has been shown to reactivate fetal hemoglobin (HbF) production and reduce the need for blood transfusions in ß-thalassemia patients. However, some patients show a minor response or no response to thalidomide. In view of its potential side effects, targeted prescription of thalidomide is imperative. We initially aimed to explore the relevance of HBG2 (rs7482144), BCL11A (rs11886868, rs4671393, rs766432 and rs1427407) and HBS1L-MYB (rs9399137, rs4895440 and rs4895441) single nucleotide polymorphisms (SNPs) in thalidomide response. Eight SNPs were investigated by PCR and DNA sequencing, and their roles in thalidomide response in Chinese ß-thalassemia patients were assessed. Results demonstrated that minor alleles of four SNPs were associated with an increased main response risk (rs7482144: P = 0.015; rs9399137: OR = 4.911, P = 0.029; rs4895440: OR = 4.522, P = 0.040; and rs4895441: OR = 4.522, P = 0.040). For patients with non-transfusion-dependent thalassemia (NTDT), with an increase in the minor allele numbers of rs7482144 (P = 0.011), rs9399137 (P = 0.013), rs4895440 (P = 0.011) and rs4895441 (P = 0.011), Hb increments after treatment were increased significantly as well. The cumulative effects of patients carrying any combination of one or three significant minor alleles included a gradually increased main response risk compared to those without the significant minor alleles (P = 0.040-0.018, OR = 8.556-11.000). Furthermore, Hb increments after treatment correlated with cumulative numbers of minor alleles in the four significant SNPs among patients with NTDT (P = 0.001). It was demonstrated that SNPs in HBG2 and HBS1L-MYB contributed significantly to thalidomide response in Chinese patients with ß-thalassemia and that the cumulative number of minor SNP alleles may serve as good predictors of treatment response in this population.

The PU.1-Modulated MicroRNA-22 Is a Regulator of Monocyte/Macrophage Differentiation and Acute Myeloid Leukemia.

MicroRNA-22 (miR-22) is emerging as a critical regulator in organ development and various cancers. However, its role in normal hematopoiesis and leukaemogenesis remains unclear. Here, we detected its increased expression during monocyte/macrophage differentiation of HL-60, THP1 cells and CD34+ hematopoietic stem/progenitor cells, and confirmed that PU.1, a key transcriptional factor for monocyte/macrophage differentiation, is responsible for transcriptional activation of miR-22 during the differentiation. By gain- and loss-of-function experiments, we demonstrated that miR-22 promoted monocyte/macrophage differentiation, and MECOM (EVI1) mRNA is a direct target of miR-22 and MECOM (EVI1) functions as a negative regulator in the differentiation. The miR-22-mediated MECOM degradation increased c-Jun but decreased GATA2 expression, which results in increased interaction between c-Jun and PU.1 via increasing c-Jun levels and relief of MECOM- and GATA2-mediated interference in the interaction, and thus promoting monocyte/macrophage differentiation. We also observed significantly down-regulation of PU.1 and miR-22 as well as significantly up-regulation of MECOM in acute myeloid leukemia (AML) patients. Reintroduction of miR-22 relieved the differentiation blockage and inhibited the growth of bone marrow blasts of AML patients. Our results revealed new function and mechanism of miR-22 in normal hematopoiesis and AML development and demonstrated its potential value in AML diagnosis and therapy.

A Case of Hereditary Spherocytosis Caused by a Novel Homozygous Mutation in the SPTB Gene Misdiagnosed as ß-Thalassemia Intermedia Due to a KLF1 Gene Mutation.

We report a rare case of hereditary spherocytosis (HS) and hereditary persistence of fetal hemoglobin (Hb) (HPFH) complicated with a ß-thalassemia (ß-thal) trait and a Krüppel-like factor 1 (KLF1) gene mutation misdiagnosed as ß-thal intermedia (ß-TI) due to a high percentage of Hb F. The proband presented with pale skin, jaundice and splenomegaly. Analysis of the thalassemia gene indicated ßcodon 17/ßA (HBB: c.52A>T), while Hb analysis showed significantly increased Hb F levels. The proband was diagnosed to carry ß-TI, and a blood transfusion regimen together with iron chelation treatment was recommended. Due to the difference between the phenotype and genotype, next generation sequencing (NGS) was performed and the proband was found to carry a homozygous mutation on the SPTB gene combined with a heterozygous mutation in KLF1. An eosin-5-maleimide binding test (EMA-BT) showed that the mean fluorescence intensity decreased by 47.1%. The proband was finally diagnosed with HS and HPFH complicated with a ß-thal trait and the high percentage of Hb F was believed to be ascribed to the KLF1 gene mutation, which is frequent in areas where thalassemia is prevalent. For patients with a ß gene mutation accompanying significantly high percentage of Hb F, the diagnosis of ß-TI could be warranted, and the influence of the KLF1 gene mutation should be carefully excluded to avoid misdiagnosis of other types of hereditary hemolytic diseases.

The histone demethylase PHF8 promotes adult acute lymphoblastic leukemia through interaction with the MEK/ERK signaling pathway.

Adult acute lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid progenitor cells that is associated with a high risk of relapse and poor prognosis. Thus, novel pathogenic mechanisms and therapeutic targets need to be explored. Histone methylation is one of the most significant chromatin post-translational modifications. Here, we show that the histone demethylase PHF8 is highly expressed in a large number of ALL clinical specimens and that PHF8 expression is associated with ALL progression. PHF8 knockdown inhibits proliferation and promotes the apoptosis of ALL cells in vitro as well as attenuates tumor growth in vivo. PHF8 transcriptionally upregulates MEK1, a key molecule in the MEK/ERK pathway, at least partially by directly binding to its promoter, thereby activating the MEK/ERK pathway. In addition, we found that an inhibitor of the MEK/ERK pathway, PD184352, subsequently suppresses PHF8 expression. Thus, PHF8 forms a positive feedback loop with the MEK/ERK pathway, and PHF8 knockdown enhances the lethality of PD184352 in ALL cells. In conclusion, this study identifies oncogenic functions of PHF8 in adult ALL and suggests a novel epigenetic strategy for disease intervention.

Clinical trial on the effects of thalidomide on hemoglobin synthesis in patients with moderate thalassemia intermedia.

To investigate the efficacy and safety of thalidomide in patients with thalassemia intermedia (TI). Patients with a confirmed diagnosis of TI who met the trial criteria and signed consent forms were prescribed oral thalidomide 50 mg qn for 3 months from February 2017. Complete blood counts, Hb analysis, and liver and kidney functions were monitored monthly during treatment and any differences were compared before and after treatment. Patients with Hb increments > 2.0 g/dL were termed main responders (MaR), and those with Hb increments between 1.0 and 2.0 g/dL as minor responders (MiR), otherwise they were termed non-responders. Relevance analysis was performed to explore parameters predicting Hb increments after treatment. Adverse effects during treatment were carefully recorded. The overall response rate (ORR = MaR + MiR) and MaR rates were 78.6 and 50% after 1 month of treatment, respectively, and 85.7 and 71.4% after 3 months treatment. At the end of the treatment period, Hb and HbF increased by 2.5 ± 1.8 g/dL and 2.5 ± 1.6 g/dL, while bilirubin, lactate dehydrogenase, and the nucleated red blood cell count (NRBC) were significantly decreased, while the reticulocyte count significantly increased. Correlation analysis showed that the Hb increments correlated significantly with the ratio of HbF before treatment (r = 0.683, P = 0.007) rather than age, Hb, reticulocyte count, and NRBC before treatment. Adverse events during treatment were mild, and drug reduction or withdrawal from the trial was not required. Thalidomide had rapid and significant effects in patients with TI, and also, it is safe and convenient. But larger scale clinical trials will be required to confirm our conclusions. TRIAL REGISTRATION: NCT02995707, https://www.clinicaltrials.gov/ct2/show/NCT03184844?term=thalidomide+thalassemia&rank=1 .

Low-order aberration correction of the TMT tertiary mirror prototype based on a warping harness.

A warping harness is proposed to simply and efficiently correct low-order aberrations that occur during manufacturing and operation of a telescope. For the Thirty Meter Telescope (TMT) tertiary mirror, the issue to be solved by the warping harness is particularly challenging due to its complicated load conditions and limited mounting space. In this study, first, a new type of whiffletree-based warping harness configuration applied to a »-prototype TMT tertiary mirror is presented and optimized using finite element analysis (FEA) to improve the output precision of the moment actuator. Next, based on the new configuration, a simulation method for a correction process is proposed. The results show that the root mean square value of the mirror-surface error converged from 64.9 to 25.4 nm after correction, which satisfied the requirement document of TMT. Finally, combined with the analysis and calculation results, the moment actuator testing system with high-precision displacement-force-strain is established to assess the system errors. The tests of the moment actuator displacement, stress, strain-output precision, linearity, and repeatability are completed, and all errors were found to be within a controllable range. The results show the validity and feasibility of the designed warping harness, which can prove its applicability in more complicated conditions and, to a certain degree, broaden the application scope of the warping harness.