Clinical Features and Blood Indicators for Severity and Prognosis in COVID-19 Patients.

BACKGROUND: This study aimed to analyze the clinical manifestations and blood indicators to deepen the understanding of Coronavirus disease 2019 (COVID-19). METHODS: COVID-19 patients admitted to C10 West Ward, Tongji Hospital in Wuhan City ("West Ward") between January 31 and March 28, 2020, were retrospectively analyzed. RESULTS: A total of 61 COVID-19 patients were hospitalized, wherein the non-critical Group had 30 cases, while the critical group had 31 (including 14 survivors and 17 deaths). Age, the proportion of fever cases, white blood cell (WBC), basophils, red blood cell (RBC), hemoglobin, lactate dehydrogenase (LDH), C-reactive protein (CRP), high-sensitivity troponin, pro-BNP (brain natriuretic peptide), prothrombin time (PT), and D-dimer were higher in the critical group while lymphocytes, eosinophils, albumin were lower compared with those of the non-critical group (all p < 0.05). WBC (p = 0.008), basophils (p = 0.034), and LDH (p = 0.005) of the death subgroup climbed remarkably in comparison with those of the survival subgroup. CONCLUSIONS: Advanced age, high fever, increases in indicators such as WBC, basophils, CRP, LDH, high-sensitivity troponin, pro-BNP, and D-dimer, and decreases in indicators, including lymphocytes, eosinophils, and albumin, might forebode a critical condition.

[Comparison of results of prenatal diagnosis by different techniques for fetuses with increased nuchal translucency].

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) and trio-whole exome sequencing (trio-WES) for fetuses with increased nuchal translucency (NT) thickness. METHODS: Sixty two pregnant women who had visited Urumqi Maternal and Child Care Health Hospital between June 2018 and June 2020 for NT ≥ 3.0 mm at 11 ~ 13+6 gestational weeks were selected as study subjects. Relevant clinical data were collected. The patients were divided into 3.0 ~ ＜3.5 mm (n = 33) and ≥3.5 mm groups (n = 29). Chromosome karyotyping analysis and chromosomal microarray analysis were carried out. And trio-WES analysis was performed on 15 samples with NT thickening but negative CMA results. The distribution and incidence of chromosomal abnormalities in the two groups were compared by using chi-square test. RESULTS: The median age of the pregnant women was 29 years old (22 ~ 41 years old), the median thickness of NT was 3.4 mm (3.0 ~ 9.1 mm), and the median gestational age at the detection was 13+4 weeks (11+5 ~ 13+6 weeks). Chromosome karyotyping analysis has detected 12 cases of aneuploidies and 1 case of derivative chromosome. The detection rate was 20.97% (13/62). CMA has detected 12 cases of aneuploidies, 1 case of pathogenic CNV and 5 cases of variant of uncertain significance (VUS), with a detection rate of 29.03% (18/62). The aneuploidy rate for the NT ≥ 3.5 mm group was higher than that for the 3.0 ≤ NT < 3.5 mm group [3.03% (1/33) vs. 41.38% (12/29), χ² = 13.698, P < 0.001]. There was no statistically significant difference between the two groups in the detection rate of fetal pathogenic CNV and VUS (χ² = 0.028, P > 0.05). Trio-WES analysis of 15 samples with negative CMA result and no structural abnormality has identified 6 heterozygous variants, including SOS1: c.3542C>T (p.A1181V) and c.3817C>G (p.L1273V), COL2A1: c.436C>T (p.P146S) and c.3700G>A (p.D1234N), LZTR1: c.1496T>C (p.V499A), and BRAF: c.64G>A (p.D22N), respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), all of the variants were rated as VUS. CONCLUSION: NT thickening can indicate chromosome abnormality, and CMA and trio-WES may be used for the prenatal diagnosis.

Efficacy of recombinant human interleukin-11 in preventing and treating oral mucositis after chemotherapy for patients with acute leukemia.

OBJECTIVE: This study aimed to investigate the clinical effects of recombinant human interleukin-11 (rhIL-11) gargle on preventing and treating oral mucositis (OM) after chemotherapy for acute leukemia. METHODS: This single-site, prospective, observer-blinded, nonrandomized controlled trial was conducted on 74 patients with acute leukemia, who were divided into the experimental and control groups. The patients in the experimental group were treated with IL-11 gargle, and those in the control group were treated with sodium bicarbonate gargle. We examined the time and severity of oral mucositis, severity and duration of associated pain, healing time of mucositis, effects of OM on eating, and levels of T-cell subset indicators before and after treatment to evaluate the effects of IL-11 treatment. RESULTS: The proportion of patients with severe OM was significantly lower in the experimental group than in the control group. Mucositis occurred later in the experimental group compared with the control group. The degree and duration of pain, ulcer healing time, and effects on eating were lower in the experimental group compared with the control group. Following treatment, the levels of all T-cell subset indicators improved in each of the two groups. However, the rate of improvement was significantly higher in the experimental group than in the control group. These differences were statistically significant (P < 0.05). CONCLUSIONS: IL-11 gargle reduced the severity of OM after chemotherapy for acute leukemia. Treatment with IL-11 relieved pain, promoted healing, and improved the curative effect of the condition, making it worthy of clinical promotion.

Carbon Metabolism and the ROS Scavenging System Participate in Nostoc flagelliforme's Adaptive Response to Dehydration Conditions through Protein Acetylation.

Acetylation represents an extensively occurring protein post-translational modification (PTM) that plays a key role in many cellular physiological and biochemical processes. However, studies on PTMs such as acetylation of lysine (LysAc) in cyanobacteria are still rare. In this study, a quantitative LysAc approach (acetylome) on the strains of Nostoc flagelliforme subjected to different dehydration treatments was conducted. We observed that starch contents were significantly accumulated due to dehydration treatments, and we identified 2474 acetylpeptides and 1060 acetylproteins based on acetylome analysis. Furthermore, an integrative analysis was performed on acetylome and nontargeted metabolism, and the results showed that many KEGG terms were overlapped for both omics analyses, including starch and sucrose metabolism, transporter activity, and carbon metabolism. In addition, time series clustering was analyzed, and some proteins related to carbon metabolism and the ROS scavenging system were significantly enriched in the list of differentially abundant acetylproteins (DAAPs). These protein expression levels were further tested by qPCR. A working model was finally proposed to show the biological roles of protein acetylation from carbon metabolism and the ROS scavenging system in response to dehydration in N. flagelliforme. We highlighted that LysAc was essential for the regulation of key metabolic enzymes in the dehydration stress response.

Proteome profiling reveals changes in energy metabolism, transport and antioxidation during drought stress in Nostoc flagelliforme.

BACKGROUND: Drought is an important abiotic stress that constrains the growth of many species. Despite extensive study in model organisms, the underlying mechanisms of drought tolerance in Nostoc flagelliforme remain elusive. RESULTS: We characterized the drought adaptation of N. flagelliforme by a combination of proteomics and qRT-PCR. A total of 351 differentially expressed proteins involved in drought stress adaptation were identified. It was found that the expression of several nutrient influx transporters was increased, including molybdate ABC transporter substrate binding protein (modA), sulfate ABC transporter substrate-binding protein (sbp) and nitrate ABC transporter (ntrB), while that of efflux transporters for toxic substances was also increased, including arsenic transporting ATPase (ArsA), potassium transporter (TrkA) and iron ABC transporter substrate-binding protein (VacB). Additionally, photosynthetic components were reduced while sugars built up during drought stress. Non-enzymatic antioxidants, orange carotenoid protein (OCP) homologs, cytochrome P450 (CYP450), proline (Pro) and ascorbic acid (AsA) were all altered during drought stress and may play important roles in scavenging reactive oxygen species (ROS). CONCLUSION: In this study, N. flagelliforme may regulates its adaptation to drought stress through the changes of protein expression in photosynthesis, energy metabolism, transport, protein synthesis and degradation and antioxidation. HIGHLIGHTS: • A total of 351 DEPs involved in adaptation to drought stress were identified. • Changes in the expression of six OCP homologs were found in response to drought stress. • Differential expression of transporters played an important role in drought stress adaptation. • Most PSII proteins were downregulated, while PSI proteins were unchanged in response to drought stress. • Sugar metabolism was upregulated in response to drought stress.

Expression of Serum PSA, Nesfatin-1, and AMH in Patients with Polycystic Ovary Syndrome.

Insulin resistance and hyperandrogenism are the leading causes of polycystic ovary syndrome (PCOS). Therefore, it has great significance to study the expression levels of PSA, nesfatin-1, and AMH. To provide some reference for clinical diagnosis and treatment of polycystic ovary syndrome (PCOS), the expression levels of PSA, nesfatin-1, and AMH in serum of patients with polycystic ovary syndrome (PCOS) were investigated. The experimental group consisted of 200 patients with polycystic ovary syndrome treated in Shanghai Huashan Hospital from July 2018 to July 2019. The control group consisted of 150 healthy women without pregnancy. The PSA, nesfatin-1, and AMH levels in serum were detected by chemiluminescence immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA). The serum levels of prostate-specific antigen (PSA) and anti-Mullerian hormone (AMH) were 16.53 ± 0.67pg/ml and 10.75 ± 4.02pg/ml in the experimental group (PCOS patients), which were significantly higher than those in the control group (3.27 ± 0.43pg/ml and 5.18 ± 1.84pg/ml, respectively), while the inhibitive factors in the experimental group (1.89 ± 0.99mg/ml) were significantly higher than those in the control group (1.10 ± 0.97mg/ml). There was no significant difference in nesfatin-1. The levels of PSA and nesfatin-1, nesfatin-1, and AMH and the levels of PSA and AMH in patients with polycystic ovary syndrome were positively correlated, and the differences were statistically significant. The levels of PSA, nesfatin-1, and AMH in patients with polycystic ovary syndrome of different ages were different, and the differences were significant and negatively correlated with the age increasing. PSA, nesfatin-1, and AMH levels in patients with polycystic ovary syndrome were significantly different from those in control nonpregnant women. There was a certain correlation between the levels of PSA, nesfatin-1, and AMH, and age. The results have specific clinical reference significance for the diagnosis and treatment of patients with polycystic ovary syndrome.

First 40Ar/39Ar analyses of Australasian tektites in close association with bifacially worked artifacts at Nalai site in Bose Basin, South China: The question of the early Chinese Acheulean.

The recently discovered Nalai site is one of the Bose Basin localities, which is key to studying the earliest bifaces in China. The Nalai site has yielded an abundance of lithic artifacts, including bifaces and tektites in close association. The total fusion 40Ar/39Ar method was applied to four tektites discovered beside and contemporaneous with bifaces in the red laterite sediments of the upper levels of the T4 terrace (layers 4 and 5). Our 40Ar/39Ar data with a weighted mean age of 809 ± 12 ka provide for the first time unequivocal dates for bifacial production at Bose, broadly consistent with the precise Australasian tektite age of 788.1 ± 2.8 ka, recently published by other investigators. The relatively important errors reported here suggest sample contamination by clasts or bubbles for the oldest aliquots and alteration for the younger ones. The lithic assemblage from layers 4 and 5 of the Nalai site is quite similar to that found at other sites in the Bose Basin. The assemblages are dominated by choppers, but bifaces, picks, and unifaces give a Mode 2 and Acheulean-type character to the series. The high frequency of the round tongue-shaped tip, a low elongation index, and a wide and thick base characterize the Large Cutting Tools. These results contribute to resolving ongoing debates on the timing and origin of bifaces and the Acheulean in China.

Safety and Efficacy of Facial Fat Grafting Under Local Anesthesia.

BACKGROUND: Facial fat grafting under local anesthesia has been widely performed in outpatient departments and private settings in China. The present study aimed to evaluate the safety and efficacy of facial fat grafting under local anesthesia. METHOD: A retrospective study was conducted on 155 patients who underwent facial fat grafting. The clinical data were recorded. Preoperative and postoperative two-dimensional images were acquired to evaluate the effect of facial fat grafting on refining facial contouring, rejuvenation as well as deformity reconstruction. The complications were recorded to assess the safety of the approach. RESULT: All the facial fat grafting procedures were performed successfully under local anesthesia. A majority of the patients who underwent one or more sessions of facial fat grafting under local anesthesia were satisfied with the cosmetic results. No severe complications occurred in these patients. CONCLUSIONS: In the present study, remarkable and natural improvements of facial contouring, rejuvenation as well as deformity reconstruction were achieved with facial fat grafting in most patients. Thus, the procedures performed under local anesthesia by experienced surgeons are safe. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Horse versus rabbit antithymocyte globulin in immunosuppressive therapy of treatment-naïve aplastic anemia: a systematic review and meta-analysis.

The first-line formulation of antithymocyte globulin (ATG) remains unknown. We aimed to systematically review evidence to compare the efficacy and safety profiles of different ATGs. We did a systematic review and meta-analysis of randomized controlled trials (RCTs) and cohort controlled studies comparing horse and rabbit ATG in immunosuppressive therapy of treatment-naïve aplastic anemia. We searched The Cochrane Library, PubMed, EMBASE, ClinicalTrials.gov , and conference proceedings of American Society of Hematology and European Society for Blood and Marrow Transplantation annual meetings. The outcomes were 3-, 6-, and 12-month response; early mortality; relapse; and evolution. We pooled hazard ratios for relapse and odds ratios (ORs) for other outcomes using fixed-effect or random-effect models based on the heterogeneity. This study was registered with PROSPERO, number CRD42016036945. We included 1636 participants from three RCTs and 11 cohort controlled studies. Allocation to horse ATG increased 6-month response events by 86% compared with rabbit ATG. The benefit of horse ATG was mainly driven by increase in studies with non-Asian (OR 95% CI = 2.39 (1.54-3.69), p < 0.0001) and good partial response criterion (OR 95% CI = 2.73 (1.53-4.89), p = 0.0007). The early mortality and evolution were similar between groups. Compared with rabbit ATG, horse ATG had superior remission by 6 months and equivalent safety profiles in patients with treatment-naïve AA. Evidence for further responses beyond 6 to 12 months was limited.

Bone marrow stromal cells induced activation of nuclear factor κB signaling protects non-Hodgkin's B lymphoma cells from apoptosis.

The microenvironment encompassing a variety of non-malignant cells in close proximity with malignant tumor cells has been well known to significantly affect the behavior of tumor cells. In this study, we therefore studied the mechanism of bone marrow stromal cells in protection of lymphoma cells from spontaneous apoptosis. We demonstrated that adhesion of the freshly isolated lymphoma B cells to bone marrow stromal cells or freshly isolated lymphoma stromal cells inhibited B cell spontaneous apoptosis in culture. This inhibition of apoptosis correlated with decreased cleavage of caspase-3/8 and increased activation of canonical and non-canonical NF-κB signaling pathway. In addition to BAFF signaling which has been reported as a functional determinant for B lymphoma cell survival in the bone marrow environment, we demonstrated RANKL from BMSCs works synergistically with BAFF to activate NF-κB signaling pathway and thus protects lymphoma B cells from spontaneous apoptosis.

Comparison of porcine anti-human lymphocyte globulin and rabbit anti-human thymocyte globulin in the treatment of severe aplastic anemia: a retrospective single-center study.

OBJECTIVES: To compare the safety and efficacy of porcine antilymphocyte globulin (pALG) and rabbit antithymocyte globulin (rATG) in treating severe aplastic anemia (SAA). METHODS: Seventy-seven patients with SAA that received immunosuppressive therapy between July 2004 and December 2013 at the Department of Hematology, the Second Affiliated Hospital of Xi'an Jiaotong University, were retrospectively analyzed. Forty-five patients received treatment including pALG (pALG group), and 32 patients received treatment including rATG (rATG group). Effective treatment rates between the two groups 1 yr after the treatment were compared; Kaplan-Meier 5-yr survival curve and log-rank test compared survival rates between the groups. All adverse responses were recorded. RESULTS: The 1-yr overall response rate in the pALG group (83.78%) was significantly higher than that in the rATG group (66.67%, P = 0.036), and the 5-yr overall survival rate in the pALG group (82.22%) was also higher than that in the rATG group (68.75%), but the difference was not statistically significant (P = 0.32). The incidence of adverse events was similar in the two groups, and no treatment-related deaths occurred. CONCLUSIONS: The efficacies, survival, and safety profiles of pALG-based treatments are similar to or even better than those of rATG-based treatments. These results may help guide the clinical use of pALG in immunosuppressive therapy for SAA.

Extended Course and Increased Dose of Initial Chemotherapy for Extranodal Nasal Type Natural Killer/T (NK/T)-Cell Lymphoma in Patients <60 Years Old: A Single-Center Retrospective Cohort Study.

BACKGROUND Extranodal NK/T-cell lymphoma (ENKTL) of the nasal type is highly invasive and relatively resistant to chemotherapy. This study aimed to assess the efficacy and safety of an extended chemotherapy regimen with increased dose intensity. MATERIAL AND METHODS This was a retrospective cohort study of 69 patients <60 years old with an ECOG score 0-2 treated for ENKTL at the Second Affiliated Hospital of Xi'an Jiaotong University between January 2004 and December 2013. The outcomes were compared between patients who received >8 courses of high-intensity chemotherapy (n=37) vs. 6-8 courses (n=18) and <6 courses (n=14) of conventional chemotherapy. Regimens included improved CHOP, CHOP-E, EPOCH, MAED, MMED, SMILE, and Hyper-CVAD with an increased dose intensity in the >8 courses group. RESULTS The mean follow-up was 52 months (8 to 82 months). Remission rate did not differ significantly when compared among the 3 groups after 3 courses of chemotherapy (83.8%, 77.8%, and 78.6%, respectively, overall P=0.834), but the 5-year overall survival (OS) differed significantly (63.5%, 45.1%, and 22.9%, respectively, overall P=0.030), as did progression-free survival (PFS) (59.1%, 36.0%, and 15.1%, respectively, overall P=0.020), disease-free survival (DFS) (54.1%, 35.5%, and 12.9%, respectively, overall P=0.022), and total relapse rate throughout follow-up (37.04%, 50.0%, and 88.89%, respectively, overall P=0.027). There were no differences in adverse effects among the 3 groups. CONCLUSIONS These results suggest improved OS, PFS, DFS, and relapse rate in young patients with ENKTL receiving >8 courses of high-intensity chemotherapy.

High-Intensity Chemotherapy is Associated with Better Prognosis in Young Patients with High-Risk Diffuse Large B-Cell Lymphoma: A 10-Year Single-Center Retrospective Cohort Study.

BACKGROUND Patients <60 years old with high-risk diffuse large B-cell lymphoma (DLBCL) receiving standard RCHOP(E) treatment display high relapse rates. Here, we compared this standard regimen to a high-intensity regimen in terms of recurrence and long-term survival. MATERIAL AND METHODS Newly diagnosed DLBCL patients <60 years old who were treated at the Second Hospital Affiliated with Xi'an Jiaotong University between January 2004 and December 2013 (n=198, 18-60 years) were included in the study. The high-intensity group included 107 patients (54.0%) who received >8 courses of chemotherapy (high-dose CHOP, CHOP-E, EPOCH, MAED, MMED, and HyperCVAD). The control group included 91 patients (46.0%) who received 6-8 courses of CHOP-based treatment. Response rate (RR), survival, relapse, and adverse effects were compared. RESULTS Baseline characteristics of the patients were similar between the 2 groups. Median follow-up was 64.5 months. RR in the high-intensity and control groups was 88.8% and 84.6% (P=0.387), respectively; 5-year overall survival was 66.4% and 36.3% (P<0.001), respectively; 5-year progression-free survival was 56.1% and 28.6% (P<0.001), respectively; 5-year disease-free survival was 54.2% and 24.2% (P<0.001), respectively; and relapse rate during follow-up was 29.5% and 67.5% (P<0.001), respectively. There were no significant differences in adverse effects between the 2 groups. CONCLUSIONS High-intensity chemotherapy is associated with better prognosis of patients <60 years old with newly diagnosed high-risk DLBCL.

[The effects of continuous positive airway pressure ventilation on hypersensitive C reaction protein and 8-isoprostane in patients with obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To observe the effect of continuous positive airway pressure ventilation on hypersensitive C reaction protein (hsCRP) and 8-isoprostane in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: A total of 78 OSAHS patients were enrolled and monitored by polysomnography (PSG) in January to March, 2013. Another 40 healthy persons were chosen as controls during the same time. According to apnea hypopnea index (AHI) and oxygen saturation, the patients were divided into mild, moderate and severe groups. Blood and urinary 8-isoprostane and hsCRP levels were detected before and after monitoring. After continuous positive airway pressure treatment for three months, blood and urinary 8-isoprostane and hsCRP were also detected in three groups. RESULTS: (1) In OSAHS patients, blood 8-isoprostane levels before and after sleep monitoring were (273.80±55.83) ng/L and (337.18±56.28) ng/L urinary 8-isoprostane (35.65±7.08) ng/L and (48.30±14.17) ng/L, hsCRP (7.63±6.10) µg/L and (9.68±8.55)µg/L, respectively. Each parameter reached a significant difference before and after sleep (P<0.05). (2) The levels of blood CRP and urinary 8-isoprostane in the control group before sleep were (4.56±2.43) µg/L, (264.14±33.61) ng/L, (32.77±9.61) ng/L, after sleep were (4.33±2.08) µg/L, (284.27±47.51) ng/L, (31.13±8.24) ng/L. All the levels were less than those of OSAHS group (P<0.05). (3) The levels of blood 8-isoprostane in mild, moderate and severe groups after monitoring were (308.16±53.48) ng/L, (327.36±59.05) ng/L, (340.39±55.31) ng/L respectively, and urinary 8-isoprostane were (35.23±11.28) ng/L, (38.30±10.89) ng/L, (44.57±12.69) ng/L, hsCRP were (5.63±4.26) µg/L, (6.96±4.43) µg/L, (8.92±7.84) µg/L. None of these three parameters showed significant difference between the three groups (P>0.05). However, compared with the control group, blood and urine 8-isoprostane and hsCRP levels of any groups had significant differences (all P values<0.05). (3) There was no significant difference in the levels of hsCRP and 8-isoprostane after sleep between the three groups in OSAHS (P>0.05). (4) Urinary 8-isoprostane level after PSG was positively correlated with hsCRP (r=0.498, P<0.01). Either 8-isoprostane or hsCRP level was correlated with AHI (r=0.479, r=0.550; P<0.01). 8-isoprostane and hsCRP levels were positively correlated with time of blood hemoglobin oxygen saturation below 90% (r=0.413, r=0.502; P<0.01). (5) After continuous positive airway pressure treatment, the levels of 8-isoprostane and hsCRP both in blood or urine were decreased in the three groups of OSAHS patients (P<0.05). CONCLUSIONS: Long term intermittent hypoxia in patients with OSAHS results in enhanced oxidative stress reaction and over-generated inflammatory mediators. There is a positive correlation between oxidative stress and inflammatory mediators, which promotes each other, leading to the organ dysfunction induced by hypoxia.

Potential mechanisms of ZiGongDing in treating HPV-induced cervical intraepithelial neoplasia: a network pharmacology and experimental verification study.

The onset of cervical intraepithelial neoplasia (CIN) is strongly associated with persistent infection caused by high-risk human papillomavirus (HPV). ZiGongDing (ZGD), a traditional Chinese medicine, has progressed to clinical application in HPV-induced CIN treatment, yet the underlying mechanism remains unclear. The objective of this paper is to explore the mechanism of ZGD in treating HPV-induced CIN by integrating a combination of network pharmacology and experimental validation. The active ingredients and targets of ZGD were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. CIN-related targets were sourced from GeneCards and the Online Mendelian Inheritance in Man (OMIM) database. Protein-protein interaction (PPI) and functional enrichment analyses were conducted to determine the potential molecular mechanism. The herb-active ingredient-target network was constructed by Cytoscape software. To further validate the therapeutic mechanism, molecular docking and in vitro experiments were performed. In this study, we identified 60 active ingredients in ZGD and 46 common targets in of CIN treatment. The PPI network analysis revealed estrogen receptor 1 (ESR1) as a pivotal target in ZGD against CIN. Functional enrichment analysis showed that the estrogen signaling pathway was mostly enriched, and ESR1 was involved. The herb-active ingredient-target network and relative literature identified cnidimol B as the primary active ingredient. Molecular docking demonstrated a strong binding affinity between ESR1 and cnidimol B. Cellular experiments revealed that cnidimol B could significantly decrease the viability of HeLa and CaSki cells. Moreover, the expression of ESR1 was notably upregulated in HeLa and CaSki cells after treatment with cnidimol B. Our study proposes a novel mechanism underlying ZGD against CIN, which involves the modulation of ESR1. This insight lays a solid foundation for further exploring and optimizing ZGD's therapeutic potential.

Chronic myeloid leukemia with two rare fusion gene transcripts of atypical BCR::ABL: A case report and literature review.

RATIONALE: Imatinib is a standard treatment for Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML), but its efficacy in rare BCR::ABL variants is underexplored. PATIENT CONCERNS: A 67-year-old woman was admitted to the Second Affiliated Hospital of Xi'an Jiaotong University in March 2022 due to elevated white blood cells. DIAGNOSIS: Karyotype analysis revealed clonal abnormalities involving the variant t(9;22) and positive results for atypical BCR::ABL variants (e14a3 and e13a3). The clinical diagnosis was CML, chronic phase, Ph+, with rare BCR::ABL-e13a3- and BCR::ABL-e14a3-positive findings. INTERVENTION: The patient was administered daily imatinib mesylate (400 mg). OUTCOMES: After 4 weeks, a swift molecular response was observed: BCR::ABL-e13a3 transcript level at 2.82 × 10-1 (28.24%), and BCR::ABL-e14a3 transcript level at 4.68 × 10-1 (46.76%). Within 3 months, a complete cytogenetic response was achieved, with a Ph chromosome ratio of 0. Early molecular response was evident as BCR::ABL-e13a3 transcript level reached 5.11 × 10-3 (0.51%), and BCR::ABL-e14a3 transcript level at 6.26 × 10-3 (0.63%). The imatinib mesylate treatment continued without significant toxicity. LESSONS: This case emphasizes the potential effectiveness of imatinib mesylate in managing rare BCR::ABL fusion gene variants of CML. Screening for these atypical variants is advised for suspected CML patients who test negative for common BCR::ABL fusion gene variants. The presented case underscores the positive outcomes achieved with imatinib treatment for a patient with rare BCR::ABL variants, contributing valuable insights for the management of similar cases. Screening for unusual fusion gene variants should be a consideration in CML diagnosis for comprehensive treatment strategies.

Development and validation of a nomogram to predict poor efficacy of imatinib in the treatment of newly diagnosed chronic phase chronic myeloid leukemia patients.

Background: Imatinib is the most widely used tyrosine kinase inhibitor (TKI) in patients with newly diagnosed chronic-phase chronic myeloid leukemia(CML-CP). However, failure to achieve optimal response after imatinib administration, and subsequent switch to second-generation TKI therapy results in poor efficacy and induces drug resistance. In the present study, we developed and validated a nomogram to predict the efficacy of imatinib in the treatment of patients newly diagnosed with CML-CP in order to help clinicians truly select patients who need 2nd generation TKI during initial therapy and to supplement the risk score system. Methods: We retrospectively analyzed 156 patients newly diagnosed with CML-CP who met the inclusion criteria and were treated with imatinib at the Second Affiliated Hospital of Xi'an Jiao Tong University from January 2012 to June 2022. The patients were divided into a poor-response cohort (N = 60)and an optimal-response cohort (N = 43) based on whether they achieved major molecular remission (MMR) after 12 months of imatinib treatment. Using univariate and multivariate logistic regression analyses, we developed a chronic myeloid leukemia imatinib-poor treatment (CML-IMP) prognostic model using a nomogram considering characteristics like age, sex, HBG, splenic size, and ALP. The CML-IMP model was internally validated and compared with Sokal, Euro, EUTOS, and ELTS scores. Results: The area under the curve of the receiver operator characteristic curve (AUC)of 0.851 (95% CI 0.778-0.925) indicated satisfactory discriminatory ability of the nomogram. The calibration plot shows good consistency between the predicted and actual observations. The net reclassification index (NRI), continuous NRI value, and the integrated discrimination improvement (IDI) showed that the nomogram exhibited superior predictive performance compared to the Sokal, EUTOS, Euro, and ELTS scores (P < 0.05). In addition, the clinical decision curve analysis (DCA) showed that the nomogram was useful for clinical decision-making. In predicting treatment response, only Sokal and CML-IMP risk stratification can effectively predict the cumulative acquisition rates of CCyR, MMR, and DMR (P<0.05). Conclusion: We constructed a nomogram that can be effectively used to predict the efficacy of imatinib in patients with newly diagnosed CML-CP based on a single center, 10-year retrospective cohort study.

Preliminary experience on treatment of infantile hemangioma with low-dose propranolol in China.

UNLABELLED: We aimed to assess the efficacy and safety of low-dose propranolol for treatment of infantile hemangiomas (IHs) in China. Our prospective study included data from 89 patients with IH, aged 1-12 months. Plasma renin activity, angiotensin II, and aldosterone were measured before initiation of propranolol therapy. Patients were administered propranolol (0.75-1 mg/kg/day) under close observation. The volume, texture, and color of lesions were used to evaluate efficacy. Safety endpoints included heart rate, systolic and diastolic blood pressures, alanine transaminase, aspartate transaminase, thyroid function tests, and fasting blood glucose. Adverse effects were recorded. Mean plasma angiotensin II concentration in patients with IH was higher than that in age-matched healthy children, whereas mean plasma renin activity was lower. Mean aldosterone level was higher at 1-3 months but lower at 4-12 months, than values reported previously. After propranolol therapy for 6 months, IH regression was classed as grade IV in 44 patients (49.4 %), grade III in 21 patients (23.6 %), and grade II in 24 patients (27.0 %); none were grade I. Mild adverse effects, including diarrhea, restless sleep, nausea, cold extremities, and hypoglycemia, occurred in 12 patients (13.5 %). Slight decreases in heart rate and blood pressure occurred in all patients (p < 0.05). The IHs of four patients (4.5 %) relapsed after treatment cessation at 4-5 months. CONCLUSION: Low-dose propranolol is effective and safe for Chinese children with IH, and larger-scale studies are merited. Mechanisms underlying IH pathogenesis, and possible involvement of the renin-angiotensin-aldosterone system, deserve study.

Comprehensive Analysis of Novel Genes and Pathways Associated with Osteogenic Differentiation of Adipose Stem Cells.

Background: Adipose-derived stem cells (ADSCs) are an important alternative source of mesenchymal stem cells (MSCs) and show great promise in tissue engineering and regenerative medicine applications. However, identifying the novel genes and pathways and finding the underlying mechanisms regulating ADSCs osteogenic differentiation remain urgent. Methods: We downloaded the gene expression profiles of GSE63754 and GSE37329 from the Gene Expression Omnibus (GEO) Database. We derived differentially expressed genes (DEGs) before and after ADSC osteogenic differentiation, followed by Gene Ontology (GO) functional and KEGG pathway analysis and protein-protein interaction (PPI) network analysis. 211 differentially expressed genes (142 upregulated genes and 69 downregulated genes) were aberrantly expressed. GO analysis revealed that these DEGs were associated with extracellular matrix organization, protein extracellular matrix, and semaphorin receptor binding. Conclusions: Our study provides novel genes and pathways that play important roles in regulating ADSC osteogenic differentiation, which may have potential therapeutic targets for clinic.

Analysis of influencing factors of community-acquired pneumonia with deep venous thrombosis in elderly communities.

BACKGROUND: Community-acquired pneumonia (CAP) is one of the common infectious diseases that threaten human health, venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary thromboembolism (PTE), is a global health care problem. Acute infection and age ≥70 years are important risk factors for VTE in internal medicine inpatients. There is increasing evidence that acute infectious diseases caused by bacterial and viral infections can induce coagulation, platelet (PLT) activation and inhibit the activity of anticoagulant factors. However, there is no consensus on whether patients with CAP suffer from DVT. Finding out the clinical characteristics and risk factors of DVT in elderly patients with CAP is helpful for early identification of high-risk patients with VTE and timely prevention, which can significantly reduce the occurrence of VTE in hospitals. METHODS: Data was collected from 505 patients with CAP aged ≥70 years old hospitalized in the Department of Respiratory and Critical Care Medicine. 133 patients with DVT were selected as the DVT group. DVT score and risk grading were performed for all patients using Padua. Fifty-seven cases were diagnosed as having severe pneumonia, including 50 cases diagnosed as having septic shock. Padua, D-dimer, between the DVT group and the control group, the severe pneumonia group and the non-severe pneumonia group, and the severe pneumonia DVT group and the control group were compared. RESULTS: (I) The incidence of DVT with severe pneumonia was much higher than with non-severe pneumonia (P<0.001). The incidence of DVT in patients with septic shock and non-septic shock was 74.0% (37/50) and 28.6% (2/7) respectively (P=0.0154). (II) There were significant differences in Padua scores between the DVT group and the control group and between the severe pneumonia group and non-severe pneumonia group (P<0.001). (III) There were significant differences in D-dimer level between the DVT group and the control group and between the severe pneumonia group and the non-severe pneumonia group (P<0.001). (IV) Regression analysis indicated the central venous catheter (CVC), D-dimer value, and Padua score were significantly correlated with thrombosis (P=0.042, <0.001, 0.043). CONCLUSIONS: Severe pneumonia in elderly patients and septic shock may be complicated by DVT, and central venous catheterization and D-dimer are closely related to thrombosis.