Targeting SIRT4/TET2 Signaling Alleviates Human Keratinocyte Senescence by Reducing 5-hydroxymethylcytosine Loss.

Skin aging is characterized by wrinkle formation and increased frailty and laxity, leading to the risk of age-related skin diseases. Keratinocyte is an important component of the epidermis in skin structure, and keratinocyte senescence has been identified as a pivotal factor in skin aging development. Because epigenetic pathways play a vital role in the regulation of skin aging, we evaluated human skin samples for DNA hydroxymethylation (5-hydroxymethylcytosine; 5-hmC) and SIRT4 expressions. Results found that both 5-hmC and SIRT4 showed a significant decrease in aged human skin samples. To test the results in vitro, human keratinocytes were cultured in H2O2, which modulates skin aging in vivo. However, H2O2-induced keratinocytes showed senescence-associated protein expression and significant downregulation of 5-hmC and SIRT4 expressions. Moreover, 5-hmC-converting enzymes ten eleven translocation 2 (TET2) showed a decrease and enhanced TET2 acetylation level in H2O2-induced keratinocytes. However, the overexpression of SIRT4 in keratinocytes alleviates the senescence phenotype, such as senescence-associated protein expression, decreases the TET2 acetylation, but increases TET2 and 5-hmC expressions. Our results provide a novel relevant mechanism whereby the epigenetic regulation of keratinocytes in skin aging may be correlated with SIRT4 expression and TET2 acetylation in 5-hmC alteration. Our study may provide a potential strategy for antiskin aging, which targets the SIRT4/TET2 axis involving epigenetic modification in keratinocyte senescence.

Internal standard optimization advances sensitivity and robustness of ratiometric detection method.

We design a p-aminothiophenol (pATP) modified Au/ITO chip to determine nitrite ions in lake water by a ratiometric surface-enhanced Raman scattering (SERS) method based on nitrite ions triggering the transformation of pATP to p,p'-dimercaptoazobenzene (DMAB). Intriguingly, by using the SERS peak (at 1008 cm-1) from benzoic ring deforming as an internal standard instead of the traditional peak at 1080 cm-1, the detection sensitivity of the method was improved 10 times.

Drug Analysis of Voriconazole Combined with Granulocyte Colony Stimulating Factor.

BACKGROUND: The aim of the study was to improve the clinical cognition of leukemia-like reaction caused by voriconazole and granulocyte colony-stimulating factor and to avoid misdiagnosis or delayed diagnosis. METHODS: A case of drug analysis of Voriconazole combined with granulocyte colony stimulating factor was retrospectively analyzed and related literature was reviewed. RESULTS: Blood routine of the patient on July 29: WBC 13.48 x 109/L, neutrophil 85.3%, lymphocyte 13.4%, hemoglobin 111 g/L, platelet 285 x 109/L. Vancomycin was given to prevent intracranial infection. Lumbar puncture was performed on July 30, cerebrospinal fluid was sent for routine and biochemical examination, leukocytes were 0.15 x 109/L, monocytes 45%, polynuclear cells 55%, protein 1.172 g/L, Acinetobacter baumannii and Candida clorbicus were detected in sputum culture, vancomycin and meropenem static sites were given to prevent intracranial secondary infection. Fungi were detected in urine culture, and voriconazole was given to prevent fungal infection. Blood routine: White blood cell 0.61 x 109/L, neutrophil 23%, lymphocyte 73.8%, red blood cell 2.65 x 1012/L, hemoglobin 77 g/L, platelet 17 x 109/L, bone marrow was extracted after medication. Bone marrow images show poor myelodysplasia, with granulocytes dominated by protoearly cells. Subsequent flow cytometry, chromosomal karyotype, and fusion gene analysis were performed to exclude the possibility of leukemia. Flow cytometry showed that the proportion of myeloid primordial cells was not high, the granulocytes were mainly at the early and young stage, no abnormal phenotype was observed in erythrocytes, monocytes and NK cells, no obvious mature B lymphocytes were observed, and the ratio of CD4+/CD8+ was decreased. Karyotype results showed that there was no mitotic phase. The results of fusion gene analysis showed that the fusion gene was negative or lower than the detection sensitivity. Voliconazole was stopped first, and granulocyte colony stimulating factor was stopped 3 days later. Two weeks later, blood and bone marrow images basically recovered, white blood cell 7.88 x 109/L, neutrophil 46.3%, lymphocyte 48.2%, hemoglobin 126 g/L, platelet 142 x 109/L, bone marrow hyperplasia active. The proportion of three series is roughly normal. CONCLUSIONS: The reason for the occurrence of leukemia-like reaction in this patient was considered to be related to voriconazole and granulocyte colony stimulating factor, cessation of voriconazole and granulocyte colony stimulating factor, and recovery of blood and bone marrow images. In the clinical use of voriconazole and granulocyte colony stimulating factor, close attention should be paid to the drug interaction and individualized medication should be carried out to ensure the safety of medication.

Responses of precipitation and water vapor budget on the Chinese Loess Plateau to global land cover change forcing.

There have been notable changes in precipitation patterns on the Loess Plateau (LP) of China in recent decades, and numerous attribution studies have focused on sea surface temperature anomalies and atmospheric circulation changes induced by aerosols and greenhouse gases emission. However, the influences of global land use and land cover change (LULCC) as an important forcing factor in the climate system on regional precipitation remains poorly understood. In this study, we quantified the impacts of LULCC on precipitation and the water vapor budget in the LP region, utilizing data from LULCC forcing experiments conducted by the sixth phase of the Coupled Model Intercomparison Project (CMIP6). Although global LULCC forcing exerted a negative effect on long-term mean precipitation on the LP region from 1850 to 2014, the different response characteristics were detected during different time periods. The global LULCC caused a decrease of 14 mm in annual precipitation during the period of 1850-1960. Conversely, from 1961 to 2014, it led to an increase of 6.4 mm, which is largely attributed to the enhanced water vapor transport along the southern boundary and westerly belt of the LP region. Moreover, from the perspective of the net water vapor balance of the entire LP, although LULCC caused net water vapor export during both periods 1850-1960 and 1961-2014, the export during the latter period (0.20 × 104 kg s-1) was smaller than that during the former period (0.28 × 104 kg s-1), indicating that the global expansion of grassland and cropland, along with the continuous rise in the leaf area index from 1961 to 2014, contributed to retaining more water vapor within the LP, which in turn was more favorable for precipitation. These findings provide valuable insights into the reasons behind precipitation variations in the LP region, emphasizing that global vegetation restoration and greening play a significant role in improving precipitation in ecologically fragile areas.

Global, regional, and national burden of incidence, prevalence, and years lived with disability for facial fractures from 1990 to 2019: a systematic analysis for the Global Burden of Disease study 2019.

BACKGROUND: Facial fractures are common injuries causing cosmetic, functional, and psychological damage. The purpose of this study was to assess the incidence, prevalence, and years lived with disability (YLDs) of facial fractures from 1990 to 2019 using the Global Burden of Disease (GBD). METHODS: Detailed data for the disease burden of facial fractures were obtained from online available public data (Global Health Data Exchange) derived from the GBD study. The incidence, prevalence, and YLDs of facial fractures from 1990 to 2019 were analyzed by country, region, age, gender, sociodemographic index (SDI), and cause. The age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized YLDs rate (ASYR), and estimated annual percentage change (EAPC) were calculated to evaluate the disease burden and quantify the trends over time. The main causes of facial fractures in different years and ages were assessed. RESULTS: Globally, there were 8.9 million incident cases, 1.5 million cases prevalent cases, and 98.1 thousand years YLDs in 2019. Compared with 1990, the number of incident cases, prevalent cases, and YLDs increased, while ASIR (EAPC, - 0.47; 95% uncertainty interval [UI], - 0.57 to - 0.37), ASPR (EAPC, - 0.39; 95% UI, - 0.46 to - 0.31), ASYR (EAPC, - 0.39; 95% UI, - 0.47 to - 0.32) showed a downward trend. The high SDI region held the highest ASIR, ASPR, and ASYR both in 1990 and 2019, such as New Zealand, Slovenia, and Australia. The burden was higher in men than in women from 1990 to 2019, while the ASRs in women exceeded that of men in the elderly. The ASIR peaked in the young adult group, however, the ASPR and ASYR increased with age. Falls and road injuries were the leading causes of facial fractures. CONCLUSIONS: Facial fractures continue to cause a heavy burden on public health worldwide. More targeted strategies need to be established to control the burden of facial fractures.

CAA-derived IL-6 induced M2 macrophage polarization by activating STAT3.

BACKGROUND: Tumor-associated macrophages (TAMs) are the most abundant types of immune cells in the tumor microenvironment (TME) of breast cancer (BC). TAMs usually exhibit an M2 phenotype and promote tumor progression by facilitating immunosuppression. This study aimed to investigate the effect of CAA-derived IL-6 on macrophage polarization in promoting BC progression. METHODS: Human BC samples and adipocytes co-cultured with 4T1 BC cells were employed to explore the properties of CAAs. The co-implantation of adipocytes and 4T1 cells in mouse tumor-bearing model and tail vein pulmonary metastasis model were constructed to investigate the impact of CAAs on BC malignant progression in vivo. The functional assays, qRT-PCR, western blotting assay and ELISA assay were employed to explore the effect of CAA-derived IL-6 on macrophage polarization and programmed cell death protein ligand 1 (PD-L1) expression. RESULTS: CAAs were located at the invasive front of BC and possessed a de-differentiated fibroblast phenotype. CAAs facilitated the malignant behaviors of 4T1 cells in vitro, and promoted 4T1 tumor growth and pulmonary metastasis in vivo. The IHC staining of both human BC specimens and xenograft and the in vitro experiment indicated that CAAs could enhance infiltration of M2 macrophages in the TME of 4T1 BC. Furthermore, CAA-educated macrophages could enhance malignant behaviors of 4T1 cells in vitro. More importantly, CAAs could secret abundant IL-6 and thus induce M2 macrophage polarization by activating STAT3. In addition, CAAs could upregulate PD-L1 expression in macrophages. CONCLUSIONS: Our study revealed that CAAs and CAA-educated macrophages enhanced the malignant behaviors of BC. Specifically, CAA-derived IL-6 induced migration and M2 polarization of macrophages via activation STAT3 and promoted macrophage PD-L1 expression, thereby leading to BC progression.

Recent advances in RNA sample preparation techniques for the detection of SARS-CoV-2 in saliva and gargle.

Molecular detection of SARS-CoV-2 in gargle and saliva complements the standard analysis of nasopharyngeal swabs (NPS) specimens. Although gargle and saliva specimens can be readily obtained non-invasively, appropriate collection and processing of gargle and saliva specimens are critical to the accuracy and sensitivity of the overall analytical method. This review highlights challenges and recent advances in the treatment of gargle and saliva samples for subsequent analysis using reverse transcription polymerase chain reaction (RT-PCR) and isothermal amplification techniques. Important considerations include appropriate collection of gargle and saliva samples, on-site inactivation of viruses in the sample, preservation of viral RNA, extraction and concentration of viral RNA, removal of substances that inhibit nucleic acid amplification reactions, and the compatibility of sample treatment protocols with the subsequent nucleic acid amplification and detection techniques. The principles and approaches discussed in this review are applicable to molecular detection of other microbial pathogens.

Nano Self-Assemblies of Caffeic Acid-Fibronectin Mimic a Peptide Conjugate for the Treatment of Corneal Epithelial Injury.

Rapid corneal re-epithelialization is important for corneal wound healing. Corneal epithelial cell motility and oxidative stress are important targets for therapeutic intervention. In this study, we covalently conjugated the antioxidant caffeic acid (CA) with a bioactive peptide sequence (PHSRN) to generate a CA-PHSRN amphiphile, which was formulated into nanoparticular eye drops with an average size of 43.21 ± 16 nm. CA-PHSRN caused minimal cytotoxicity against human corneal epithelial cells (HCECs) and RAW264.7 cells, exhibited an excellent free radical scavenging ability, and remarkably attenuated reactive oxygen species (ROS) levels in H2O2-stimulated HCECs. The antioxidant and anti-inflammatory activities of CA-PHSRN were assessed in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The results show that CA-PHSRN treatment effectively prevented LPS-induced DNA damage and significantly reduced the levels of LPS-induced pro-inflammatory cytochemokines (i.e., iNOS, NO, TNF-α, IL-6, and COX-2) in a dose-dependent manner. Moreover, using a rabbit corneal epithelial ex vivo migration assay, we demonstrated that the proposed CA-PHSRN accelerated corneal epithelial cell migration and exhibited high ocular tolerance and ocular bioavailability after topical instillation. Taken together, the proposed CA-PHSRN nanoparticular eye drops are a promising therapeutic formulation for the treatment of corneal epithelial injury.

A Case of AML1-ETO Positive Acute Myeloid Leukemia Morphologically Similar to Chronic Myelogenous Leukemia.

BACKGROUND: The goal was to study the role of the morphology, immunophenotype, karyotype and fusion gene expression in a patient with diagnosis of AML1-ETO positive acute myeloid leukemia. METHODS: A case of AML1-ETO positive acute myeloid leukemia morphologically similar to chronic myelogenous leukemia was reported. The results of the morphology, immunophenotype, karyotype and fusion gene expression were analyzed by reviewing relevant literature. RESULTS: The patient was a young boy, at the age of 13, with clinical manifestations of intermittent fatigue and fever. Blood routine: White blood cell 142.6 x 109/L, Red blood cell 0.89 x 1012/L, Hemoglobin 41 g/L, Platelet 23 x 109/L, primitive cells account for 5%. Bone marrow smear: Granulocyte system hyperplasia is obvious, visible at each stage, primitive cells account for 17%, eosinophils, basophils, and phagocytic blood cells were observed. Flow cytometry showed myeloid primitive cell population was 4.14%, immature and mature granulocytes cell population was 85.22%, and eosinophil cell population was 0.61%. The results showed that the proportion of myeloid primitive cell was high, the expression of CD34 was enhanced, the expression of CD117 was partially absent, the expression of CD38 was weakened, the expression of CD19 was weak, and a few cells expressed CD56, and the phenotype was abnormal. The proportion of granulocyte series increased and the nucleus shifted to the left. The proportion of erythroid series was decreased, and the expression of CD71 was weakened. The results of fusion gene showed AML1-ETO positive. Karyotype analysis showed clonogenic abnormality t(8;21)(q22;q22). CONCLUSIONS: The peripheral blood and bone marrow images of patients with t(8;21)(q22;q22) AML1-ETO positive are the manifestations of chronic myelogenous leukemia, suggesting that cytogenetics and molecular genetics play an irreplaceable role in the diagnosis of acute myeloid leukemia, and the comprehensive diagnostic efficiency is significantly better than that of morphology.

A Case of AML1/ETO Positive Child with Acute Myeloid Leukemia with Poor Prognosis.

BACKGROUND: The aim was to improve the understanding of an AML1/ETO positive child with acute myeloid leukemia with poor prognosis. METHODS: A case of AML1/ETO positive child with acute myeloid leukemia with poor prognosis was reported. The bone marrow cell morphology, multi-parameter flow cytometry, cytogenetic or molecular genetic test results were analyzed by reviewing relevant literature. RESULTS: The patient was a young girl with clinical manifestations of respiratory tract infection. Bone marrow smears showed that myeloid primordial cells accounted for 13%, some granulocyte cell bodies are enlarged, visible pathological phenomena such as cytoplasmic vacuoles, binuclear grains, ring rods, and pseudo pelgerhuet malformations were seen (Figure 1). Flow cytometry: abnormal myeloid original cells (12.33%), expression of CD34 and HLA - DR, CD38, CD56, part of the expression of CD117, weak expression of CD13, CD33, MPO, CD19, cCD79a (Figure 2). Chromosome karyotype analysis showed that the chromosome karyotype of peripheral blood was 46, XX, t(8;21)(q22;q22). The quantitative detection result of AML1/ETO fusion gene was 42.15%, and mutations of NRAS, ASXL2, TP53 and TET2 genes were detected by second-generation sequencing. Combined with the above results, AML1/ETO positive with acute myeloid leukemia was diagnosed. CONCLUSIONS: Cytogenetics or molecular genetics is the gold standard for identification of positive AML1/ETO fusion gene. Morphological heterogeneity of AML1/ETO positive AML cells is large, which limits the morphological diagnosis of bone marrow cells to a certain extent, and the comprehensive diagnostic efficiency is significantly better than that of morphology. Leukemia fusion gene AML1/ETO refers to the fusion of AML1 gene located on human chromosome 21q22 and ETO gene 8q22, which is the most common fusion gene in acute myeloid leukemia (AML). This paper reports a case of an AML1/ETO positive child with acute myeloid leukemia with poor prognosis admitted to our hospital and reviews relevant literature.

Clinical Characteristics and Diagnosis of Acute Myeloid Leukemia with CD56-Blastic Plasmacytoid Dendritic Cell Neoplasm.

BACKGROUND: The aim of the study was to investigate the clinical characteristics and diagnosis of acute myeloid leukemia with CD56- blastic plasmacytoid dendritic cell neoplasm. METHODS: The clinical characteristics and diagnosis of CD56-blastic plasmacytoid dendritic cell neoplasm and review related literature of 3 patients with acute myeloid leukemia were retrospectively analyzed. RESULTS: This paper reports 3 cases and all were elderly men. The bone marrow features of three patients suggested the diagnosis of acute myeloid leukemia with blastic plasmacytoid dendritic cell neoplasm. Case 1: Flow cytometry showed that visible abnormalities in myeloid cells, accounting for 19.25% of nucleated cells, the phenotypes were CD117+, CD38+, CD33+, CD13+, CD123+, HLA-DR+, CD34 partial+, CD64 partial+ and TDT partial+, CD7-, CD11b-, CD22-, CD15-, CD5-, CD2-, CD20-, CD19-, CD10-, CD4-, CD14-, CD36, MPO-, CD9-, cCD79a-, cCD3-, mCD3-, CD5-. In addition, a group of abnormal plasmacytoid dendritic cells was observed, accounting for 13.83% of nuclear cells (CD2-, TDT partial+, CD303+, CD304+, CD123+, CD34-, HLA-DR+, and CD56-). Second generation sequencing: RUNX1 mutation 41.7%, DNMT3A mutation 41.3%. Case 2: Flow cytometry showed that visible abnormalities in myeloid cells, accounting for 33.66% of nucleated cells, express the strong expression of CD34 expression of CD117, HLA - DR, CD38, CD13, CD33, CD123, the TDT, no expression of MPO, cCD3, and cCD79a, conform to the AML phenotype. In addition, a group of abnormal plasmacytoid dendritic cells was observed, accounting for 26.87% of nucleated cells (CD303+, CD304+, CD123++, HLA-DR+, CD33+, CD36+, CD7 dim, CD4+, CD56-, TDT-). Second generation sequencing: The mutations of FLT3, CBL, RUNX1, and SRSF2 were 7.4%, 7.5%, 53.3%, and 29.9%. Case 3: Flow cytometry showed that visible abnormalities in myeloid cells, accounting for 23.76% of nucleated cells, the phenotypes were CD117++, HLA-DR++, CD34++, CD38+, CD13+, CD123+, CD7 partial+, and CD33 partial+, MPO-, TDT-, cCD3-, cCD79a-. In addition, a group of abnormal plasmacytoid dendritic cells was observed, accounting for 16.66% of nuclear cells (TDT+, CD303+, CD304+, CD 123++, HLA-DR+, CD38+, CD7+, CD56-, CD34-). CONCLUSIONS: Acute myeloid leukemia with CD56-blastic plasmacytoid dendritic cell neoplasm is extremely rare and no special clinical manifestations are found, and the diagnosis is based on bone marrow cytology and immunophenotyping. There is no standard regimen for treatment of acute myeloid leukemia with mature blastic plasmacytoid dendritic cell neoplasm, and the prognosis depends on the progression of acute myeloid leukemia.

A Case of Acute Mixed Cell Leukemia Resembling AML1-ETO Positive Acute Myeloid Leukemia.

BACKGROUND: The aim of the study was to improve the understanding of complex karyotype acute mixed cell leukemia containing pseudo Chediak-Higashi granules. METHODS: A case of acute mixed cell leukemia resembling AML1-ETO positive acute myeloid leukemia was reported. The results of morphological, immunophenotypic, and cytogenetic tests were analyzed by reviewing relevant literature. RESULTS: The patient was a young boy with clinical manifestations of recurrent fever. Bone marrow smear: Granulocyte system hyperplasia is obvious, visible at each stage, primitive cells account for 12%. These cells are large in volume, mostly round or class round, with abundant cell mass, stained gray blue, unbalanced development of some nuclear plasma, abnormal cytoplasmic staining, and visible "sunrise red" -like changes. Typical Auer bodies, pseudo Chadiak-Higashi granules and phagocytic erythroid substances were observed. The nuclei are irregular in shape, distorted and depressed, with fine chromatin and prominent large nucleoli. Bone marrow was extracted 3 days later, the bone marrow smear showed 65% primitive cells. The morphology of primitive cells was similar to that of 3 days ago. The results of flow cytometry showed that the primary/naive T cells in the samples possessed nuclear cells. Flow cytometry showed two groups of abnormal cells. One group accounted for 3.87% of nuclear cells and was a primitive/naive T-cell phenotype, mainly expressing: CD34+, CD7+, CD5+, CD2dim+, MPO-, CCD3 + part, CD3-, CD4-, CD8 -, CD117 -, CD13-, CD33-, HLA - DR -, CD10-, CD11b-, CD56-. The other group which accounted for 79.8% of the nuclear cells was monocyte phenotype, mainly expressing: CD34-, CD117-, CD13+ small amount, CD33+, HLA-DR-, CD11b+, CD14+, CD15+, CD36+, CD56+, CD64+, CD4+, CD85J+, CD85K + part. It matched the immunophenotype of acute mixed cell leukemia (T/MMPAL). Immunophenotypic leukemia-related fusion genes were negative, and karyotype analysis results were 45, XY, T (11; 12)(p13; Q13), -12-17, + mar [12]/90 < n > 4, idem x 2 [6]/46, XY. Combined with the above results, acute mixed cell leukemia was diagnosed. CONCLUSIONS: The flow cytometry is the gold standard in the diagnosis of acute mixed cell leukemia. The diagnosis of acute mixed cell leukemia requires the combination of clinical manifestations, cellular morphology, immunology, cytogenetics and molecular biology, and the comprehensive diagnosis efficiency is obviously better than that of morphology.

Clinical Characteristics and GBA Gene Mutation Analysis of Gaucher Disease Type I.

BACKGROUND: The aim was to investigate the clinical characteristics and GBA gene mutation analysis of Gaucher disease type I in children. METHODS: The clinical manifestations, GBA gene mutations, and review related literature of 3 children with Gaucher disease type I were retrospectively analyzed. RESULTS: Case 1: Clinical manifestations include epistaxis, pancytopenia, hepatosplenomegaly, and lymphadenopathy. Glucocerebrosidase 0.38 µmol/L/hour, c.1226A>G; p. N370S (heterozygous) mutation. Case 2: Clinical manifestations include abdominal enlargement, hemoglobin and thrombocytopenia, hepatosplenomegaly, lymph nodes were not palpable. Glucocerebrosidase 0.48 mol/L/hour, c.1246G>A; p. Gly416Ser (heterozygous) mutation and c.115 + 1G>A; p.? (heterozygous) mutation. Case 3: Clinical manifestations include anemia, pancytopenia, he-patosplenomegaly, and lymph nodes were not palpable. Glucocerebrosidase 0.41 mol/L/hour, c.1240g>C; p. Val414Leu (heterozygous) mutation and c.475C>T; p. Arg159Trp (heterozygous) mutation. CONCLUSIONS: The main clinical features of type I Gaucher disease are hepatosplenomegaly, anemia, and thrombocytopenia. Some patients also have reduced white blood cells. Enzyme activity detection is the gold standard for the diagnosis of Gaucher disease. The correlation between Gaucher disease genotype and clinical phenotype is complex. Gene mutations can affect enzyme activity and stability. The higher the degree of enzyme activity decline, the more severe the clinical phenotype.

Clinical and Laboratory Characteristics of IgM Primary Plasma Cell Leukemia.

BACKGROUND: The aim of the study was to investigate the clinical and laboratory characteristics of IgM primary plasma cell leukemia. METHODS: We retrospectively analyzed a case of clinical and laboratory characteristics of IgM primary plasma cell leukemia and review related literature of patient with primary plasma cell leukemia. RESULTS: Laboratory tests: Alanine aminotransferase 128 U/L, Aspartate aminotransferase 245 U/L, Globulin 47.8 g/L, Lactate dehydrogenase 1,114 U/L, Creatinine 111.7 mol/L, Serum calcium 2.47 mmol/L, ß2 microglobulin 8.52 µg/mL, Immunoglobulin G 31.41 g/L, D-dimer 2.34 mg/L, Prothrombin time 13.6 seconds Fibrinogen 2 g/L, White blood cell 7.38 x 109/L, Red blood cell 3.46 x 1012/L, Hemoglobin 115 g/L, Platelet 7 x 109/L, and 12% Primitive naive cells can be seen in peripheral blood smear. Bone marrow smear: Accounted for 52% of original cells, the cell size, shape is irregular, the edge is not neat, the cell quality is rich, stained gray blue, cytoplasmic staining uneven, some devouring blood cells can be seen in the cytoplasm or unknown substance, the nucleus shape is irregular, visible distortion and fold, is visible on the part of the nuclei cavitation sample inclusions, chromatin is meticulous, partly visible large nucleoli. Flow cytometry results showed abnormal cell group held 23.85% of nuclear cells, expression of CD38, CD138, CD117, cKappa, partly CD20, weak expressing CD45, not express CD27, CD19, CD56, CD200, CD81, cLambda. It was a monoclonal plasma cell with an abnormal phenotype, consistent with a plasma cell tumor. Immunofixation electrophoresis results showed that the serum M protein was 22.80 g/L, which was IgG-κ type, the serum free KAP light chain was 232.69 mg/L, the serum free LAM light chain was 5.37 mg/L, and the rFLC (κ-FLC: λFLC) was 43.33. The diagnosis was primary plasmacytic leukemia of light chain type. CONCLUSIONS: Primary plasma cell leukemia (pPCL) is a rare and highly aggressive plasma cell malignancy. Laboratory staff should pay more attention to and recognize the pleomorphic morphology of neoplastic plasma cells, which can enable timely clinical development of bone marrow smear, biopsy, flow cytometry, and cytogenetic tests providing help in early diagnosis and treatment.

Complex Karyotype Acute Basophilic Leukemia with Reactive Mast Cell Hyperplasia.

BACKGROUND: The goal of the study is to improve the understanding of complex karyotype acute basophilic leukemia with reactive mast cell hyperplasia. METHODS: A case of clinical and laboratory characteristics of complex karyotype acute basophilic leukemia with reactive mast cell hyperplasia and review of related literature of patient with acute basophilic leukemia were retrospectively analyzed. RESULTS: Laboratory tests: alanine aminotransferase 225 U/L, aspartate aminotransferase 129 U/L, total protein 3.0 g/L, albumin 25.0 g/L, globulin 17.8 g/L, total bilirubin 183.9 µmol/L, indirect bilirubin 65.6 µmol/L, D-dimer 13.02 mg/L, prothrombin time 19.30 S, white blood cell 37.30 x 109/L, red blood cells 2.06 x 1012/L, hemoglobin 71 g/L, platelets 13 x 109/L, and basophilic granulocyte cells 5.01 x 109/L. Bone marrow smear: a large number of abnormal primitive cells were scattered and distributed. The characteristics of these cells were as follows: the cell body size was different, most of them were round or quasi-round, the cytoplasm volume was medium, and the cytoplasm was stained gray blue. The cytoplasmic processes were visible, and basophilic particles were visible in part of the cytoplasm and/or on the nucleus. The nuclei were mostly round or almost round, with distortion and folding. The chromatin was detailed, the nucleoli varied in number, and some nucleoli were deeply stained. The cells showed double and multiple nuclei, scattered and occasionally small clumps. Bone marrow biopsy: acute myeloid leukemia, not excluding basophilic leukemia. Bone marrow molecular biology: All 29 myeloid leukemia genes, including RARA and BCR-ABL fusion genes, were negative. Flow cytometry results showed abnormal cell population which accounted for 21.98% of nuclear cells. The phenotypes are CD33++, CD38+, CD13+, CD123+, CD7+, CD36+, CD203c+, CD81+, part of CD34+, part of HLA-DR+, CD4 weak+, weak CD117+, the TDT-, cCD3-, cCD79a-, MPO-, CD11c-, CD25-, CD2-. In addition, mast cells accounted for 1.15% of nuclear cells, expressing CD203c, but not CD25 and CD2. Karyotype analysis results were 46, XY, -7, psudic (9; 19) (p24; p13.3), add (15) (p12), add (21) (q22), +r, +1 - 2 mar [cp20]. CONCLUSIONS: Acute basophilic leukemia (ABL) is a rare malignant hematologic tumor. Bone marrow smears, biopsies, flow cytometry, and cytogenetic tests play an important role in the diagnosis and differentiation of complex karyotype acute basophilic leukemia with reactive mast cell hyperplasia.

Melanocyte transplantation to skin prepared by controlled PUVA-induced sunburn-like blistering for vitiligo treatment - A pilot clinical trial.

Vitiligo is a common acquired disease of pigment loss. In lesions recalcitrant to non-invasive treatment, transplantation of cultured autologous melanocytes is an emerging choice. Conventionally, the recipient site is often prepared by laser-mediated or mechanical dermabrasion. Such preparation procedures have disadvantages including prolonged transplantation duration, long period for reepithelialization and potential scarring. We propose a method of preparing recipient sites by psoralen and controlled ultraviolet A (PUVA)-induced blistering followed by transplanting suspended melanocytes. We introduced this method in 10 patients with segmental vitiligo on their recipient site 3 to 5 days before transplantation and blistering developed in 2 to 3 days afterwards. On the day of transplantation, the blister roof could be peeled off easily without bleeding and the recipient site preparation could be completed in 20 min. The recipient site became reepithelialized within 1 week. Progressive repigmentation was observed for up to 6 months, with an average of 65.06% repigmentation in the recipient site without scarring at the end of follow-up. Hence, preparation of the recipient site by controlled PUVA-induced sunburn-like blistering can potentially facilitate melanocyte transplantation and prevent scarring.

Carriage of distinct blaKPC-2 and blaOXA-48 plasmids in a single ST11 hypervirulent Klebsiella pneumoniae isolate in Egypt.

BACKGROUND: Carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) causes serious infections with significant morbidity and mortality. However, the epidemiology and transmission mechanisms of CR-hvKP and the corresponding carbapenem-resistant plasmids require further investigation. Herein, we have characterized an ST11 K. pneumoniae strain EBSI041 from the blood sample encoding both hypervirulence and carbapenem resistance phenotypes from a patient in Egypt. RESULTS: K. pneumoniae strain EBSI041 showed multidrug-resistance phenotypes, where it was highly resistant to almost all tested antibiotics including carbapenems. And hypervirulence phenotypes of EBSI041 was confirmed by the model of Galleria mellonella infection. Whole-genome sequencing analysis showed that the hybrid plasmid pEBSI041-1 carried a set of virulence factors rmpA, rmpA2, iucABCD and iutA, and six resistance genes aph(3')-VI, armA, msr(E), mph(E), qnrS, and sul2. Besides, blaOXA-48 and blaSHV-12 were harboured in a novel conjugative IncL-type plasmid pEBSI041-2. The blaKPC-2-carrying plasmid pEBSI041-3, a non-conjugative plasmid lacking the conjugative transfer genes, could be transferred with the help of pEBSI041-2, and the two plasmids could fuse into a new plasmid during co-transfer. Moreover, the emergence of the p16HN-263_KPC-like plasmids is likely due to the integration of pEBSI041-3 and pEBSI041-4 via IS26-mediated rearrangement. CONCLUSION: To the best of our knowledge, this is the first report on the complete genome sequence of KPC-2- and OXA-48-coproducing hypervirulent K. pneumoniae from Egypt. These results give new insights into the adaptation and evolution of K. pneumoniae during nosocomial infections.

Genome resequencing-based high-density genetic map and QTL detection for yield and fiber quality traits in diploid Asiatic cotton (Gossypium arboreum).

Cotton is the most important fiber crop in the world. Asiatic cotton (Gossypium arboreum, genome A2) is a diploid cotton species producing spinnable fibers and important germplasm for cotton breeding and a significant model for fiber biology. However, the genetic map of Asiatic cotton has been lagging behind tetraploid cottons, as well as other stable crops. This study aimed to construct a high-density SNP genetic map and to map QTLs for important yield and fiber quality traits. Using a recombinant inbred line (RIL) population and genome resequencing technology, we constructed a high-density genetic map that covered 1980.17 cM with an average distance of 0.61 cM between adjacent markers. QTL analysis revealed a total of 297 QTLs for 13 yield and fiber quality traits in three environments, explaining 5.0-37.4% of the phenotypic variance, among which 75 were stably detected in two or three environments. Besides, 47 QTL clusters, comprising 131 QTLs for representative traits, were identified. Our works laid solid foundation for fine mapping and cloning of QTL for yield and fiber quality traits in Asiatic cotton.

Immunotherapy landscape analyses of necroptosis characteristics for breast cancer patients.

Necroptosis plays a major role in breast cancer (BC) progression and metastasis. Besides, necroptosis also regulates inflammatory response and tumor microenvironment. Here, we aim to explore the predictive signature based on necroptosis-related genes (NRGs) for predicting the prognosis and response to therapies. Using Lasso multivariate cox analysis, we firstly established the NRG signature based on TCGA database. A total of 6 NRGs (FASLG, IPMK, FLT3, SLC39A7, HSP90AA1, and LEF1), which were associated with the prognosis of BC patients, were selected to establish our signature. Next, CIBERSORT algorithm was utilized to evaluate immune cell infiltration levels. We compare the response to immunotherapy using IMvigor 210 database, and also compared immune indicators in two risk groups via multiple methods. The biological function of IPMK was explored via in vitro verification. Finally, our results indicated that the signature was an independent prognostic indicator for BC patients with better efficiency than other reported signatures. The immune cell infiltration levels were higher, and the response to immunotherapy and chemotherapy was better in the low-risk groups. Besides, other immunotherapy-related factors, including TMB, TIDE, and expression of immune checkpoints were also increased in the low-risk group. Clinical sample validation showed that CD206 and IPMK in clinical samples were both up-regulated in the high-risk group. In vitro assay showed that IPMK promoted BC cell proliferation and migration, and also enhanced macrophage infiltration and M2 polarization. In summary, we successfully established the NRG signature, which could be used to evaluate BC prognosis and identify patients who will benefit from immunotherapy.

Dual-directional group delays during optical topological transitions in black phosphorus-based asymmetric hyperbolic metamaterials.

We theoretically study the optical properties of TM waves when their magnetic field direction is perpendicular to the armchair and zigzag optical axes of black phosphorus, respectively. It is found that hyperbolic dispersion and elliptic dispersion coexist in periodically arranged black phosphorus multilayers. Interestingly, by tilting the symmetric multilayers to be asymmetric, the elliptical part of the original two dispersions disappears as the wavelength increases. As such only the hyperbolic dispersion remains, showing an optical topological transition. In the region of the topological transition, a large transmitted group delay (3ps) and a reflected group delay (0.2ps) of the TM waves occurs simultaneously. The corresponding group velocities are slowed down to approximately c/1000 and c/100 (c is the speed of light in a vacuum), respectively. This dual-directional group delays significantly increase the wave-matter interaction so that nonreciprocal perfect absorptions can be realized in the mid-infrared band. Such asymmetrical black phosphorus hyperbolic metamaterials can be applied to the directional, tunable, and nonreciprocal perfect absorbers and also to devices based on strong wave-matter interactions.