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Hao Huang,1,* Peng-Yang Yu,1,* Chen Wei,2 Yang-Wei Li,3 Li-Jie Liang,1 Yu-Zhang Liu,1 Li-Na Liu,1 Bai-Jun Fang,1 Yao-Mei Wang1 1Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China; 2Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China; 3Central Laboratory, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yao-Mei Wang; Bai-Jun Fang, Email wangyaomeiwym9@126.com; bjfdr_sea@163.comObjective: To examine the clinical characteristics and anemia-related factors in patients with newly diagnosed multiple myeloma (NDMM), as well as the effect and mechanism of erythroblastic islands (EBIs) and EBI macrophages in NDMM patients with anemia.Methods: We collected and analyzed clinical data to find anemia-related factors. Using flow cytometry, the numbers and ratios of erythroblasts and EBI macrophages were determined. RNA sequencing (RNA-seq) was used to determine the differences of EBI macrophages in NDMM patients with or without anemia.Results: Based on the clinical characteristics of NDMM patients with anemia, MCV, abnormal levels of albumin, osteolytic lesions, and Durie-Salmon (DS) stage are risk factors for anemia. Patients with anemia have fewer erythroblasts, erythroblastic islands (EBIs), and EBI macrophages in their bone marrow than patients without anemia. RNA-seq analysis of EBI macrophages from the bone marrow of patients with and without anemia revealed that macrophages from patients with anemia are impaired and tend to promote the production of interleukin-6, which has been demonstrated to be an essential survival factor of myeloma cells and protects them from apoptosis.Conclusion: In NDMM patients with anemia, EBI macrophages are impaired, which causes anemia in those patients. Our finding highlights the significance of EBI macrophages in anemia in NDMM patients and provides a new strategy for recovery from anemia in these patients.Keywords: anemia, central macrophages, erythroblastic islands, erythropoiesis, multiple myeloma

Hong-Mei Zhang, Xi-Yang Liu, Yu-Zhang Liu, Li-Na Liu, Quan-De Lin, Yong-Ping Song, Bai-Jun Fang Department of Hematology, Henan Institute of Haematology, Henan Cancer Hospital, the Affliated Cancer Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450008, People’s Republic of ChinaCorrespondence: Bai-Jun FangDepartment of Hematology, Henan Institute of Haematology, Henan Cancer Hospital, The Affliated Cancer Hospital of Zhengzhou University, Zhengzhou University, No. 127 Dongming Road, Zhengzhou 450008, People’s Republic of ChinaTel +86 3 716 558 7318Fax +86 3 716 558 8134Email bjfdr_sea@163.comBackground: This study aims to compare the efficacy and adverse reactions of bortezomib for treating newly diagnosed multiple myeloma (MM) through two different administration methods: intravenous (IV) injection and subcutaneous (SC) injection.Methods: A retrospective analysis was performed in 205 patients with newly diagnosed MM, who were treated by the Department of Hematopathology, Henan Cancer Hospital, from June 2009 to December 2017. These patients were divided into two groups according to the treatment methods: IV injection group, IV injection of bortezomib; SC injection group, SC injection of bortezomib.Results: After the first course of treatment, the effect of very good partial remission (VGPR) or above (≥VGPR) in the IV injection group (IV group) and SC injection group (SC group) was 31.0% and 14.3%, respectively (P=0.004), while the overall response rate (ORR) was 72.0% and 49.5%, respectively (P=0.001). From the 2nd course to the 6th course of treatment, the ORR was not statistically different between these two groups. No significant difference was found in median progression-free survival (37 vs 45 months) and overall survival (63 vs 59 months). A lower frequency of adverse events, especially Grade 3 peripheral neuropathy, was observed in SC group compared with the IV group.Conclusion: Compared with IV administration, SC bortezomib can provide a better balance between efficacy and toxicity.Keywords: multiple myeloma, bortezomib, intravenous injection, subcutaneous injection

To determine the efficacy and safety of selinexor combined with venetoclax (VEN) and azactitidine (AZA) for patients with relapsed and/or refractory acute myeloid leukemia (R/R AML) . Twelve patients with R/R AML treated with selinexor plus VEN and AZA in the Affiliated Cancer Hospital of Zhengzhou University from May 2022 to May 2023 were included. Their clinical data were retrospectively analyzed. Among the 12 R/R AML patients, 5 (41.7%) achieved complete remission (CR) , 1 (8.3%) achieved CR with incomplete hematological recovery, and 5 (41.7%) achieved partial remission. The median time to reach CR was 28 (16-59) days. The median PFS was 61 (15-300) days. The main adverse event of the regimen was hematological toxicity. No chemotherapy-related deaths were observed. The combination of selinexor plus VEN and AZA is an effective treatment for R/R AML patients.

Objectives: The psychological effects of the COVID-19 pandemic may include anxiety. However, the association between demographic and physiological factors in COVID-19 associated anxiety symptoms is poorly understood. Therefore, the present cross-sectional study was conducted to examine anxiety symptoms and associated factors among patients with the SARS-CoV-2 omicron variant during quarantine in Shanghai., Methods: The study was conducted between April 16, 2022, and May 21, 2022, at Fangcang Shelter Hospital in Shanghai, China. Data were collected using an anonymous online questionnaire. Demographic characteristics, respiratory symptoms, vaccine dose, comorbidities (such as hypertension and diabetes), type of work, and mental health symptoms were evaluated. Logistic regression was used to investigate the relationship between anxiety symptoms and risk factors. Stratification analysis was performed to investigate potential interactions., Results: A total of 2132 patients with confirmed omicron variant SARS-CoV-2 infection were enrolled. The results showed that sex, age, type of work, respiratory symptoms, and comorbidities were positively associated with anxiety symptoms. Female gender (OR = 1.47, 95% CI = 1.11-1.94), nonmanual labor (OR = 1.62, 95% CI = 1.25-2.09), respiratory symptoms (OR = 3.19, 95% CI = 2.30-4.43), and other comorbidities (OR = 1.65, 95% = 1.09-2.50)were positively associated with anxiety symptoms. A significant interaction was observed between gender and nonmanual labor (OR = 1.54, 95% = 1.29-1.85), respiratory symptoms (OR = 2.06, 95% = 1.72-2.48), and comorbidities (OR = 1.57, 95% = 1.16-2.12), such that effects were stronger in women compared to men. There were also significant interactions between age group and nonmanual labor and respiratory symptoms in their association with anxiety symptoms., Conclusions: Alleviation of respiratory symptoms, addressing comorbidities, and both psychological and psychopharmacological treatments may help reduce anxiety symptoms following infection with the SARS-CoV-2 omicron variant in mainland China., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To observe the angiogenesis effect of electroacupuncture (EA) at Shuigou acupoint (GV 26) in the treatment of cerebral ischemia, and explore the value of miRNA-7 (miR-7) in it., Methods: First, 48 mice were randomly divided into sham operation, middle cerebral artery occlusion (MCAO) model, and EA treatment groups. Then 9 mice were divided into carrier control group, miR-7 knockout group and miR-7 overexpression group (n=3 each group). Finally, 20 mice were divided into model and carrier control group, model and miR-7 knockout group, EA treatment and carrier control group and EA treatment and miR-7 overexpression group, with 3-6 mice in each group. The MCAO model was established in the MCAO and EA groups. Neurological deficit score and 2,3,5-triphenyltetrazolium chloride (TTC) staining were used to evaluate the severity of cerebral ischemia. Hematoxylin-eosin staining was used to describe basic pathological changes. Immunohistochemistry was used to quantify cerebral microvessel density. Real-time PCR and Western blot were used to detect the expression of miR-7 and its downstream target genes Krüppel-like factor 4/vascular endothelial growth factor (KLF4/VEGF) and angiopoietin-2 (ANG-2) in the ischemic cerebral cortex., Results: After EA, neurological deficit scores and infarction volumes decreased, and the density of cerebral microvessels increased. In the MCAO group, miR-7 expression was higher than that in the sham group (P<0.01). After EA at GV 26, miR-7 expression decreased (P<0.01) and the expression of downstream target genes KLF4/VEGF and ANG-2 increased as compared with the MCAO group (P<0.01). After EA combined with overexpression of miR-7, the expression of downstream target genes KLF4/VEGF and ANG-2 decreased compared to the control EA group (P<0.01). After miR-7 knockdown, the expression of KLF4/VEGF and ANG-2 increased (P<0.05 or P<0.01)., Conclusions: EA could promote angiogenesis in MCAO mice likely by inhibiting the expression of miR-7 and relieving inhibition of downstream target genes KLF4/VEGF and ANG-2., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To evaluate the efficacy and safety of Huashi Baidu Granules (HSBD) in treating patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant., Methods: A single-center retrospective cohort study was conducted during COVID-19 Omicron epidemic in the Mobile Cabin Hospital of Shanghai New International Expo Center from April 1st to May 23rd, 2022. All COVID-19 patients with asymptomatic or mild infection were assigned to the treatment group (HSBD users) and the control group (non-HSBD users). After propensity score matching in a 1:1 ratio, 496 HSBD users of treatment group were matched by propensity score to 496 non-HSBD users. Patients in the treatment group were administrated HSBD (5 g/bag) orally for 1 bag twice a day for 7 consecutive days. Patients in the control group received standard care and routine treatment. The primary outcomes were the negative conversion time of nucleic acid and negative conversion rate at day 7. Secondary outcomes included the hospitalized days, the time of the first nucleic acid negative conversion, and new-onset symptoms in asymptomatic patients. Adverse events (AEs) that occurred during the study were recorded. Further subgroup analysis was conducted in vaccinated (378 HSBD users and 390 non-HSBD users) and unvaccinated patients (118 HSBD users and 106 non-HSBD users)., Results: The median negative conversion time of nucleic acid in the treatment group was significantly shortened than the control group [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The negative conversion rate of nucleic acid in the treatment group were significantly higher than those in the control group at day 7 (91.73% vs. 86.90%, P=0.014). Compared with the control group, the hospitalized days in the treatment group were significantly reduced [10 days (IQR: 8-11 days) vs. 11 days (IQR: 10.25-12 days); P<0.01]. The time of the first nucleic acid negative conversion had significant differences between the treatment and control groups [3 days (IQR: 2-4 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The incidence of new-onset symptoms including cough, pharyngalgia, expectoration and fever in the treatment group were lower than the control group (P<0.05 or P<0.01). In the vaccinated patients, the median negative conversion time and hospitalized days were significantly shorter than the control group after HSDB treatment [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days), P<0.01; 10 days (IQR: 8-11 days) vs. 11 days (IQR: 10-12 days), P<0.01]. In the unvaccinated patients, HSBD treatment efficiently shorten the median negative conversion time and hospitalized days [4 days (IQR: 2-6 days) vs. 5 days (IQR: 4-7 days), P<0.01; 10.5 days (IQR: 8.75-11 days) vs. 11.0 days (IQR: 10.75-13 days); P<0.01]. No serious AEs were reported during the study., Conclusion: HSBD treatment significantly shortened the negative conversion time of nuclear acid, the length of hospitalization, and the time of the first nucleic acid negative conversion in patients infected with SARS-COV-2 Omicron variant (Trial registry No. ChiCTR2200060472)., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

The fabrication method plays a key role in the performance of lead magnesium niobate-lead titanate-based ceramics. (1 - w )[Pb(Mg 1/3 Nb 2/3 ) 0.67 Ti 0.33 O 3 ]- w [Pb 1-1.5 x Sm x (Mg 1/3 Nb 2/3 ) y Ti 1- y O 3 ] piezoelectric ceramics were prepared by sintering the mixture of two different crystalline phases in which two pre-sintered precursor powders were mixed and co-fired at designated ratios ( w = 0.3, 0.4, 0.5, 0.6). The X-ray diffraction results show that all the ceramics presented a pure perovskite structure. The grains were closely packed and the average size was ~5.18 μm based on observations from scanning electron microscopy images, making the ceramics have a high density that is 97.8% of the theoretical one. The piezoelectric, dielectric, and ferroelectric properties of the ceramics were investigated systematically. It was found that the properties of the ceramics were significantly enhanced when compared to the ceramics fabricated using the conventional one-step approach. An outstanding piezoelectric coefficient d 33 of 1103 pC/N and relative dielectric permittivity ε 33 / ε 0 of 9154 was achieved for the ceramics with w = 0.5.

Objective: To assess the effect and safety of Reyanning Mixture (RYN) in treating asymptomatic or mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents., Methods: This is a prospective, open-label, randomized controlled trial. Patients aged 1-17 years and diagnosed with asymptomatic or mild coronavirus disease-2019 (COVID-19) were assigned to an intervention group (RYN plus standard care) and a control group (standard care) according to a randomization list. The primary outcomes were SARS-CoV-2 negative conversion time. Secondary outcomes included negative conversion rate on days 3 and 7, hospital length of stay, symptom relief rate, new-onset symptoms of asymptomatic infected patients, and progressive disease rate. The cycle threshold (Ct) values of ORF1ab or N genes were also tested., Results: A total of 214 patients in the intervention group and 217 in the control group were analyzed. The SARS-CoV-2 negative conversion time was significantly shortened in the intervention group [5 days (interquartile range (IQR): 5-6) vs. 7 days (IQR: 6-7), P<0.01]. By days 3 and 7, the negative conversion rates were significantly higher in the intervention group (day 3: 32.7% vs. 21.2%, P=0.007; day 7: 75.2% vs. 60.8%, P=0.001). Ct values significantly increase on day 2 [ORF1ab gene: 35.62 (IQR: 29.17-45.00) vs. 34.22 (IQR: 28.41-39.41), P=0.03; N gene: 34.97 (IQR: 28.50-45.00) vs. 33.51 (IQR: 27.70-38.25), P=0.024] and day 3 [ORF1ab gene: 38.00 (IQR: 32.72-45.00) vs. 35.81 (IQR: 29.96-45.00), P=0.003; N gene: 37.16 (IQR: 32.01-45.00) vs. 35.26 (IQR: 29.09-45.00), P=0.01]. No significant difference was found in hospital length of stay between the two groups (P>0.05). Symptoms of cough were significantly improved (82.2% vs. 70.0%, P=0.02) and wheezing was significantly reduced (0.7% vs. 12.9%, P<0.01) in the intervention group compared with the control group. During the trial, no disease progression or serious adverse events were reported., Conclusion: Adding RYN to standard care may be a safe and effective treatment for children with asymptomatic and mild SARS-CoV-2 infection. (Registration No. ChiCTR2200060292)., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Correction to: European Review for Medical and Pharmacological Sciences 2022; 26 (4): 1283-1292. DOI: 10.26355/eurrev&#95;202202&#95;28121-PMID: 35253185-published online on December 15, 2022. After publication, the authors corrected the order of the author's affiliations as follows: Q.-D. Lin1,2,3,4, L.-N. Liu1,2,3,4, X.-Y. Liu1,2, Y. Yan1,2, B.-J. Fang1,2,3,4, Y.-L. Zhang1,2,3,4, J. Zhou1,2,3,4, Y.-F. Li1,2,3,4, W.-L. Zuo1,2,3,4, Y.-P. Song1,2,3,4 1Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou City, Henan Province, China 2Henan Cancer Hospital, Zhengzhou City, Henan Province, China 3Henan Key Lab of Experimental Hematology, Zhengzhou City, Henan Province, China 4Henan Institute of Hematology, Zhengzhou City, Henan Province, China There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/28121.

Objective: Severe cases of coronavirus disease 2019 (COVID-19) are expected to have a worse prognosis than mild cases. Shenhuang Granule (SHG) has been shown to be a safe and effective treatment for severe COVID-19 in a previous randomized clinical trial, but the active chemical constituents and underlying mechanisms of action remain unknown. The goal of this study is to explore the chemical basis and mechanisms of SHG in the treatment of severe COVID-19, using network pharmacology., Methods: Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was employed to screen chemical constituents of SHG. Putative therapeutic targets were predicted by searching traditional Chinese medicine system pharmacology database and analysis platform, SwissTargetPrediction, and Gene Expression Omnibus (GEO) databases. The target protein-protein interaction network and enrichment analysis were performed to investigate the hub genes and presumptive mechanisms. Molecular docking and molecular dynamics simulations were used to verify the stability and interaction between the key chemical constituents of SHG and COVID-19 protein targets., Results: Forty-five chemical constituents of SHG were identified along with 131 corresponding therapeutic targets, including hub genes such as HSP90AA1, MMP9, CXCL8, PTGS2, IFNG, DNMT1, TYMS, MDM2, HDAC3 and ABCB1. Functional enrichment analysis indicated that SHG mainly acted on the neuroactive ligand-receptor interaction, calcium signaling pathway and cAMP signaling pathway. Molecular docking showed that the key constituents had a good affinity with the severe acute respiratory syndrome coronavirus 2 protein targets. Molecular dynamics simulations indicated that ginsenoside Rg4 formed a stable protein-ligand complex with helicase., Conclusion: Multiple components of SHG regulated multiple targets to inhibit virus invasion and cytokine storm through several signaling pathways; this provides a scientific basis for clinical applications and further experiments., (Copyright © 2022 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the effectiveness and safety of Baidu Jieduan Granules (BDJDG) to treat common type coronavirus disease 2019 (COVID-19)., Methods: This multicenter, retrospective, and observational clinical trial included 230 common COVID-19 patients in Leishenshan, Huangshi, and Laohekou Hospitals in Wuhan from January 21 to March 26, 2020. The included patients were further divided into two subgroups according to the use of supplemental oxygen, mild and moderate groups. During the first 14 d of hospitalization, all patients were administered BDJDG combined with conventional Western medicine, and observed for continuous 28 d. Primary outcomes were disease progression rate and discharge rate. Secondary outcomes included negative conversion time of nucleic acid, hospitalization duration, clinical symptom subsidence time, and symptom regression rate., Results: A total of 230 common COVID-19 patients were analyzed (138 in moderate group and 92 in mild group). By day 28, the disease progression rate was 4.3% and the discharge rate was 95.7%. All mild cases recovered and were discharged from hospital. The median negative conversion time of nucleic acid of all 230 COVID-19 patients was 12 d [inter-quartile range (IQR) 3.5-17], the median hospitalization duration was 15 d (IQR 12-20). The median time to fever, cough, and fatigue recovery was 4 d (IQR 2-6), 8 d (IQR 5-12), and 8 d (IQR 5-11). The recovery rate of fever, cough, and fatigue was 94.6%, 90.5%, and 93.5%. The median time to clinical improvement was 12 d (IQR 10-17). Compared with the baseline, total leukocyte counts, neutrophil counts, lymphocyte counts, and platelet counts were increased significantly on days 7 and 14 (P<0.01). C-reactive protein markedly increased on day 3 and significantly decreased on days 7 and 14 (P<0.01). No serious adverse events occurred during treatment., Conclusion: BDJDG may be effective and safe for treatment of common type COVID-19. (Registration No. ChiCTR2000030836)., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate the expression of miR-17-5p in the plasma of patients with multiple myeloma (MM) and its role in tumorigenesis and development. Methods: Patients diagnosed with unidentified monoclonal gammopathy of undetermined significance (MGUS) or MM in Cancer Hospital of Zhengzhou University from April 2013 to April 2018 were enrolled, as well as 20 healthy volunteers. Reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-17-5p in plasma circulation and bone marrow mononuclear cells. There were 22 cases with newly diagnosed MM (NDMM), 11 cases with complete remission MM (CRMM) and 59 case with recurrent refractory MM (RRMM). The expression levels of miR-17-5p in each group were analyzed. The correlation analysis was used to evaluate the relationship between plasma miR-17-5p and the proportion of serum M protein and bone marrow plasma cells in patients with untreated multiple myeloma. Receiver operating characteristic (ROC) curve was used to evaluate the possibility of plasma miR-17-5p as a molecular marker related to MM diagnosis. After over expression or knockdown of miR-17-5p expression, CCK-8 method was used to detect the effect of miR-17-5p on the proliferation of MM cell line. The effect of miR-17-5p on the proliferation of MM cells was detected in nude mice subcutaneous tumorigenesis experiment. Results: The expression of miR-17-5p in bone marrow mononuclear cells in NDMM and RRMM group were higher than those in healthy volunteers [1.37 (0.47, 4.87), 2.68 (1.02, 5.02) vs 1.00 (1.00, 1.00), all P< 0.05], and the expression levels of miR-17-5p in plasma were also higher than those in healthy control group [1.85 (0.92, 3.51), 2.79 (1.22, 5.04) vs 1.00 (1.00, 1.00), all P< 0.05]. The expression of miR-17-5p in MM cell lines such as KMS-11, RPMI-8226, H929, MM-1R, U266B1 were higher than that in bone marrow mononuclear cells of healthy control group (3.96±0.68, 1.58±0.32, 3.51±0.55, 5.08±0.76, 3.22±0.75 vs 1.00±0, all P <0.05) ; Plasma miR-17-5p was positively correlated with the ratio of serum M protein and bone marrow plasma cells ( r =0.50, P <0.05; r =0.60, P <0.01). ROC curve showed that the specificity was 0.591 and the sensitivity was 0.900 of plasma miR-17-5p as a molecular marker related to diagnosis (area under ROC curve=0.74, cut-off value: 0.491). CCK-8 results showed that over expression of miR-17-5p increased the proliferation of RPMI-8226 and NCI-H929 cell lines at 72 hours compared with the control group (1.37±0.11 vs 1.07±0.09, 2.14±0.09 vs 1.82±0.11, both P <0.05), and low expression of miR-17-5p reduced the proliferation of NCI-H929 and MM-1R cell lines at 72 hours compared with the control group (1.38±0.09 vs 1.83±0.11, 1.45±0.10 vs 1.73±0.09, both P <0.05). The subcutaneous tumorigenesis experiment in nude mice showed that the tumor volume of miR-17-5p over expression group was larger than that of the control group [(1 865±181) vs (1 389±227) mm 3 , P <0.05], and the tumor volume of miR-17-5p low expression group was smaller than that of the control group [ (1 006±171) vs (1 389±227) mm 3 , P< 0.05]. Conclusion: miR-17-5p may play an oncogene role in MM cell lines as a plasma molecular marker related to the development of MM disease.

Sargentodoxa cuneata (Oliv.) Rehd. et Wils is a traditional Chinese medicine to treat acute appendicitis, rheumarthritis, abdominal pain, and painful menstruation for a long history. The investigation of S. cuneata led to the isolation and identification of twenty-three secondary metabolites, including two new compounds, sargentodoxosides A ( 1 ) and B ( 2 ), and twenty-one known ones ( 3-23 ). Their structural characterization was conducted by HRESIMS, 1 D and 2 D NMR spectra. All the isolated compounds were assayed for their agonistic activities against the farnesoid X receptor (FXR). Nine of the isolated compounds displayed significant agonistic effects against FXR at 0.1 µM, suggesting that they could be served as potential agents for the development of FXR agonists.

Background: Pomalidomide in combination with dexamethasone has demonstrated positive results in patients with relapsed or refractory multiple myeloma (RRMM), but no data are available in China. We conducted a multicenter, single-arm trial to examine the efficacy and safety of bioequivalent generic pomalidomide plus low-dose dexamethasone in Chinese RRMM patients., Methods: Adult (≥ 18 years of age) RRMM patients who progressed after at least two previous treatments, including bortezomib and lenalidomide, were eligible. Pomalidomide was given orally at 4 mg/day on days 1 to 21 of a 28-day cycle. Dexamethasone was given at 40 mg/day (either orally or intravenously; 20 mg/day at 75 years or older) on days 1, 8, 15, and 22 of each cycle. Treatment continued until disease progression or intolerable adverse events (AEs). The primary end point was objective response rate (ORR)., Results: Seventy-four patients were enrolled between February 2017 and February 2019. All patients had progressed within 60 days of their last therapy. 74.3% of the patients were resistant to lenalidomide, 31.1% had renal insufficiency and 33.8% had high-risk cytogenetic RRMM. The median follow-up duration was 33.0 months (range 31.1-34.8 months). The ORR was 37.8% in the overall analysis, 32.7% in lenalidomide-refractory patients, 36.0% in patients with high-risk cytogenetics and 34.8% in RRMM patients with renal impairment. The median progression-free survival was 5.7 months (95% CI 3.7-8.8 months). The median overall survival was 24.3 months (95% CI 14.4-41.1 months). The most common grade 3 and 4 treatment-emergent adverse events (TEAEs) were neutropenia (63.5%), leukopenia (37.8%), thrombocytopenia (28.4%), and anemia (31.1%). Pulmonary infection (27.0%) was the most frequent grade 3 and 4 nonhematologic TEAE. No previously unreported AEs were observed. No venous thromboembolism was reported., Conclusions: Pomalidomide in combination with low-dose dexamethasone is effective and safe in Chinese RRMM patients., Trial Registration: The study is registered at Chinese Clinical Trial Registry (ChiCTR) ( ChiCTR-OIC-17013234 , first registered on 03/11/2017)., (© 2022. The Author(s).)

With the progress of medical technology, cloning hematopoietic was found to be widely exist in normal people. Because of its clinical significance and prognosis is unclear, it is named clonal hematopoiesis of indeterminate potential(CHIP), which has been detected in blood diseases such as myelodysplastic syndrome and lymphoma, and proven to be related to poor prognosis. Recently, CHIP has been also detected in patients with multiple myeloma (MM). In this article, the definition and influencing factors of CHIP, clinical significance, prognosis and treatment in MM were reviewed.

Objective:   To explore the in vitro and in vivo experimental study of thioredoxin-1(Trx1) inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12) promoting multiple myeloma H929 cell apoptosis, investigate the relationship between the inhibitory effect of PX-12 on H929 cells and reactive oxygen species (ROS)., Materials and Methods: Inhibition of PX-12 on H929 cells in relation to reactive oxygen species (ROS), cell cycle, and apoptosis were assessed by flow cytometry. ELISA kit, IVIS Imaging, Hematoxylin and eosin (H&E) staining and immunohistochemical staining assessment were applied to assess the anti-myeloma effect in the SCID mice model established by H929EL cells., Results: PX-12 inhibited proliferation of H929 cells performed time and dose dependent style. Furthermore, it significantly induced a G2/M phase arrest of the cell cycle in H929 cells. It also increased intracellular ROS and caspase-3 activity in H929 cells indicating that cells have undergone apoptosis. There was an almost 3-5-fold decrease in tumor viability measured by the Living-Imaging system after 21 and 28 days after PX-12 injection compared with the control group. Importantly, PX-12 caused significant decrease in expression of Kappa chain in vivo assessed by immunohistochemical staining., Conclusions: The results suggest that PX-12 may be a potential strategy for the treatment of MM, and the inhibition of TRX-1 in the treatment of myeloma deserves further research.

Objective: To analyze the efficacy and safety of Daratumumab for the treatment of primary AL light chain systemic amyloidosis. Methods: Twenty one patients who were diagnosed as primary AL light chain systemic amyloidosis and treated with Daratumumab from 7 centers were retrospectively analyzed. Daratumumab was administrated as first line therapy in seven patients and 14 patients with relapsed settings. Hematological response, safety and survival were analyzed. Results: All 7 patients achieved very good partial response (VGPR) or better with first-line application of daratumumab. Three patients died, and the other four achieved organ remission. Among 14 relapsed patients, 2 patients had a difference of free light chain (dFLC) less than 20 mg/L before treatment, and 9 with a dFLC of more than 50 mg/L. All patients reached partial response (PR) or better, including 4 patients with complete response (CR), 3 with VGPR and 2 with PR. The response rate was 100% in 3 patients with dFLC 20-50 mg/L at baseline. The organ remission rate was 50% in patients with heart involvement and 58.3% in patients with kidney impairment. The overall median follow-up period was 5.3 months, and 11 months in surviving patients. One patient died of severe infection and disseminated intravascular coagulation (DIC) with stable amyloidosis. One patient switched to other regimens because dFLC elevated but did not fulfill progressive disease after 2 year application. As to safety, no grade 3/4 infusion reaction developed, and grade 1 infusion reaction occurred in 3 cases during the first infusion. Lymphocytopenia was seen in 75% patients including grade 3 or more in 30% patients. Conclusion: Daratumumab is effective to eliminate serum free light chain in both newly diagnosed and relapsed patients with systemic amyloidosis.

Objective: To study the effect of PX-12 on apoptosis of multiple myeloma (MM) cell line induced by bortezomib., Methods: MM cell line H929 cells were divided into PX-12 group, bortezomib group, combination group, and control group. 5.0 μmol/L PX-12, 20 nmol/L bortezomib, combination of the two drugs, and DMSO were given to the above mentioned group, respectively. After culture for 24, 48, and 72 hours, the changes of cell viability were observed, the MM cell activity was detected by MTT method, and the cell cycle distribution and apoptosis of each group was detected by flow cytometry. The intracellular ROS level was measured by H 2 DCFDA probe labeling., Results: MTT assay showed that after culture for 72 hours, the activity of H929 cells in PX-12 group (P<0.05) and bortezomib group (P<0.01) was significantly lower than that in the control group, while that in the combination group was decreased most significantly (P<0.01). After culture for 48 hours, cells in G1 phase in PX-12 group was decreased to 40%, while cells in S phase and G 2 /M phase was increased to 28% and 40%, respectively. The cells in bortezomib group also showed a similar distribution after being treated. After treated with PX-12 and bortezomib, the cells in G1 phase were decreased significantly to 19% and 12% in S phase, but increased significantly to 68% in G 2 /M phase, which was significantly different from PX-12 group and bortezomib group (P<0.01). After culture for 72 hours, the apoptosis rate was 71.3% in the combination group, which was significantly higher than that in PX-12 group, bortezomib group, and control group (20.6%, 33.3%, 10.6%)(P<0.01). After culture for 24 hours, the intracellular ROS level in the combination group was 12015±430.2, which was higher than that in the PX-12 group, bortezomib group, and control group (6729±352.8, 2651±228.3, 1098±164.6, respectively) (P<0.01)., Conclusion: PX-12 can increase the apoptosis of MM cell line H929 induced by bortezomib, which may be caused by increasing of ROS level.

Objective: To evaluate risk factors and available treatments of extramedullary relapse (EMR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myeloid leukemia. Methods: A total of 280 patients were retrospectively analyzed from January 2008 to December 2018 in Affiliated Cancer Hospital of Zhengzhou University. Clinical data were collected including disease patterns, pre-transplantation status, chromosome karyotype, conditioning regimen, types of donor, extramedullary disease before transplantation and graft-versus-host disease (GVHD). The log-rank test and Cox proportional hazard model were uesd for univariate analysis and multivariate analysis, respectively. Results: Twenty patients developed EMR (7.14%). The median time of EMR was 7.5 (1-123) months after allo-HSCT. The mortality of EMR was 80% (16/20). Univariate analysis identified disease patterns, second complete remission (CR2) or progressive disease before transplantation, extramedullary disease, abnormal karyotype and conditioning regimen without total body radiation as significant factors correlated to EMR ( P <0.05). Multi-variable analysis revealed that CR2 or progressive disease ( RR =3.468,95% CI 2.189-7.786), abnormal karyotype ( RR =1.494,95% CI 1.020-2.189) and extramedullary disease before transplantation ( RR =8.627,95% CI 3.921-18.452) were independent risk factors of EMR. Conclusions: The clinical outcome of EMR after allo-HSCT is poor.It is crucial to comprehensively assess and identify EMR as early as possible.

This retrospective study investigated the effect of Yiqi-Huoxue Decoction (YQHXD) on blood pressure (BP) in patients with acute ischemic stroke (AIS).A total of 72 patients with BP following AIS who received routine treatment were included in this retrospective study. Of those, 36 patients received YQHXD and were assigned to a treatment group. The other 36 patients were allocated to a control group. All patients were treated for a total of 4 months. The outcomes were assessed by systolic blood pressure (SBP), diastolic blood pressure (DBP), National Institutes of Health Stroke Scale (NIHSS) score and Barthel index scale (BIS). All outcomes were measured after 4-month treatment.After treatment, all subjects in the treatment group showed greater improvements in SBP (P < .05), DBP (P < .05), NIHSS (P < .05) score, and BIS (P < .05) than those of patients in the control group. In addition, the safety profile is similar in both groups.The findings of this study demonstrated that YQHXD may benefit on BP in patients with AIS. Future studies should focus on warranting the current results.

Background: In multiple myeloma (MM), impact of specific chromosomal translocations involving IgH (14q21 locus, including t(4;14), t(11;14), and t(14;16)) has been explored extensively. However, over 15% MM patients harboring IgH translocation with undefined partners have long been ignored., Methods: A prospective non-randomized cohort study with a total of 715 newly-diagnosed MM cases was conducted, 13.6% of whom were t(14;undefined) positive. The whole cohort was divided into four groups: no IgH split (47.7%); t(14;undefined) (13.6%); t(11;14) (17.6%); and t(4;14) or t(14;16) group (21.1%)., Results: Median OS for the four groups was 84.2, not reached (NR), 58.7, and 44.2 months, respectively, with P values for t(14;undefined) vs no IgH split, t(11;14), and t(4;14)/t(14;16) groups of 0.197, 0.022, and 0.001, respectively. In bortezomib-based group, the survival advantage gained by t(14;undefined) group was much more significant compared to t(11;14) and t(4;14)/t(14;16) groups. Importantly, t(14;undefined) turned out to be an independent predictive factor for longer OS of MM patients in multivariate analysis, especially in the context of bortezomib treatment. Similar results were also observed in the PUMCH external validation cohort., Conclusion: Collectively, our data confirmed and externally validated the favorable prognosis of the t(14;undefined) groups, especially in the era of novel agents., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To investigate the clinicopathologic features, treatment, and prognosis in patients with Castleman disease (CD) . Methods: We retrospectively analyzed the clinicopathologic data of 59 patients for whom a diagnosis of Castleman disease was confirmed using pathological examination from October 2011 to October 2019 at the Henan Cancer Hospital. The patients were divided into the following two groups as per the following clinical classifications: unicentric CD (UCD, n =47) and multicentric CD (MCD, n =12) . Data on clinical manifestations, laboratory findings, treatment, and prognosis were analyzed. Results: There was no significant difference in the median age and the ratio of male to female between the UCD and MCD. UCD was characterized by asymptomatic enlargement of the single lymph node. The main pathological type was hyaline vascular histopathology (83.0%) . Of these, 44 patients chose surgical resection, and their prognosis was good. Treatment. MCD was characterized by multiple enlarged superficial and/or deep lymph nodes with B symptoms, weakness, and hepatosplenomegaly. Anemia, hypoproteinemia, and globulin level were increased on laboratory examinations. Plasmacyte histopathology was the main pathological type and was present in about 50.0% of the subjects. Only chemotherapy was performed for these MCD patients, followed by chemotherapy or chemotherapy followed by radiotherapy, and the efficient was 58.3% (7/12) . Conclusions: UCD, characterized by asymptomatic enlargement of the single lymph node, shows good postoperative prognosis. MCD has relatively complex clinical manifestations and poor prognosis, and optimal treatment is yet to be established.

The efficacy and safety of co-transplantation of unrelated donor peripheral blood stem cells (UD-PBSCs) combined with umbilical cord mesenchymal stem cells (UC-MSCs) in refractory severe aplastic anemia-Ⅱ(RSAA-Ⅱ) were analyzed retrospectively. Fifteen patients with RSAA-Ⅱ underwent UD-PBSCs and UC-MSCs co-transplantation, among whom 14 cases had hematopoietic reconstitution without severe graft versus-host disease (GVHD). The 5-year overall survival rate was 78.57%. Combination of UD-PBSCs and UC-MSCs transplantation could be a safe and effective option for RSAA-Ⅱ.

This study aims to review the clinical efficacy and factors affecting the treatment of multiple myeloma (MM) by autologous hematopoietic stem cell transplantation (ASCT). The clinical data of 47 patients with MM from the Department of Hematology of Henan Cancer Hospital from September 2010 to July 2018 were retrospectively analyzed. At pre-transplantation of autologous cells, 25.5% were in complete remission (CR), 14.9% were in very good partial remission (VGPR) and 59.6% were in partial remission (PR). Among these cases, one case had PR after three recurrences. At post-transplantation, 51% were in CR, including two cases who received double transplantations, 27.7% were in VGPR, and 21.3% were in PR. The median follow-up time was 27.6 months (4-96 months). The 3-year progression free survival (PFS) and overall survival (OS) were 47.9% and 79.6%, respectively. The Analysis of variance (ANOVA) results revealed that factors that affected OS were international staging system (ISS) stage (P = 0.002), CR and VGPR post-transplantation (P = 0.002), while factors that affected PFS were ISS stage (P = 0.005), pre-transplant induction therapy (P = 0.032), and disease risk stratification (P = 0.017). The curative effects for PFS were CR and VGPR pre-transplantation (P = 0.013) and post-transplantation (P = 0.011). The Cox multivariate regression analysis revealed that ISS stage and CR and VGPR post-transplantation were independent prognostic factors of OS. At post-transplantation, CR and VGPR, ISS stage, and pre-transplant induction therapy were independent prognostic factors for PFS. In conclusion, ASCT can improve the clinical efficacy and survival rate of MM patients. ISS stage, CR and VGPR post-transplantation are independent prognostic factors of OS and PFS, while pre-transplant induction therapy is an independent prognostic factor for PFS., (© 2019 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Objective: To evaluate the efficacy and safety of mesenchymal stem cells in allogeneic hematopoietic stem cell transplantation for patients with refractory severe aplastic anemia (R-SAA) . Method: The clinical data of 25 R-SAA patients receiving co-transplantation of mesenchymal stem cells combined with peripheral blood stem cells from sibling donors (10 cases) and unrelated donors (15 cases) from March 2010 to July 2018 in Zhengzhou University Affiliated Tumor Hospital were retrospectively analyzed. Antithymocyte globulin (ATG) treatment was ineffective/relapsed in 11 cases, and cyclosporine (CsA) treatment ineffective/relapsed in 14 cases. Results: There were 13 male and 12 female among these patients. One patient had a primary graft failure, one patient had a poorly engraftment of platelets, and the remaining 23 patients achieved hematopoietic engraftment. The median time of granulocyte engraftment was 12.5 (10-23) days and 15 (11-25) days for megakaryocyte. Incidences of grade Ⅰ/Ⅱ acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD) were 37.5% (9/24) and 21.7% (5/23) , respectively. There was no severe GVHD and no severe complications that related to transplantation. 21 of 25 (84%) patients were alive with a median follow-up of 22.9 (1.6-107.8) months. The 5-year overall survival rate after transplantation was (83.6±7.5) %. Conclusion: The combination of mesenchymal stem cells is reliable and safe in the treatment of R-SAA in peripheral blood stem cell transplantation of unrelated donors and sibling donors, which could significantly reduce the incidence of GVHD and severe transplantation-related complications.

Background: Previous study has reported that Fuyuan Xingnao Decoction (FYXND) can be utilized for the treatment of patients with diabetes mellitus (DM) combined cerebral infarction (CI) effectively., Methods: We will search from the following databases of MEDLINE, EMBASE, Cochrane Library, PsycINFO, Global Health, Web of Science, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. All databases will be searched from the inception to the present without language limitation. Two independent authors will perform literature selection, information collection, and methodological quality assessment. Statistical analysis will be carried out using RevMan 5.3 software., Results: This study will provide accurate results on the effectiveness and safety of FYXND on DM and CI through primary and secondary outcomes. The primary outcome is neurological deficit. The secondary outcomes consist of fasting blood glucose, hemoglobin Alc, fasting insulin, quality of life, and adverse effects., Conclusions: This well-designed study will establish high quality evidence of the effectiveness and safety of FYXND for DM and CI to facilitate the clinical practice and guideline development.

Background: In this study, we will assess the efficacy and safety of metoclopramide for the treatment of acute migraine (AM)., Methods: We will comprehensively search Cochrane Library, PUMBED, EMBASE, Google Scholar, Web of Science, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from the inception to July 1, 2019 to identify any eligible studies. Only randomized controlled trials will be considered for inclusion. The study selection, data collection, and management will be completed by two authors independently. The risk of bias will be assessed using Cochrane risk of bias tool. RevMan 5.3 software will be used for statistical analysis., Results: The primary outcome includes pain intensity, as measured by visual analogue scale or others. The secondary outcomes are success rate, requirement of rescue medicine, quality of life, relapse, and adverse events., Conclusions: This study will summarize the latest evidence for the clinical efficacy and safety of metoclopramide for the treatment of AM., Prospero Registration Number: PROSPERO CRD42019142795.

Multiple myeloma (MM) is still an incurable disease, and its pathogenesis involves cytogenetics and epigenetics. In recent years, the roles of long non-coding RNAs (lncRNAs) in MM have been deeply studied by scholars. LncRNAs are defined as a class of non-protein-coding transcripts greater than 200 nucleotides in length, which are involved in a large spectrum of biological processes, including proliferation, differentiation, apoptosis, invasion, and chromatin remodeling. However, little is known about the specific mechanisms of these lncRNAs. They can act as oncogenic and/or tumor-suppressive factors in the development and progression of MM. But that how do they work remains unclear. In this review, the recent progress in the study of functional lncRNAs associated with MM was summarized and the present knowledge about their expression and roles was discussed, to provide guidance for the in-depth functional study of lncRNAs., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To analyze the clinical efficacy and possible influencing factors of autologous hematopoietic Stem cell transplantation (auto-HSCT) in the treatment of patients with multiple myeloma (MM)., Methods: Clinical data of 40 MM patients received auto-HSCT in the Department of Hematology of Henan Cancer Hospital from September 2010 to November 2017 were retrospectively analyzed, the clinical curative efficiency was summarized and the related factors were analyzed., Results: The curative efficiency of the patients before transplantation was 9(22.5%) with complete remission(CR), 5(12.5%) with very good partial remission(VGPR), 26(65%) with partial remission(PR), respectively, one of them was PR after 3 recurrences. The curative efficiency after transplantation was 22(55%) with complete remission(CR), 12(30%) with very good partial remission(VGPR), 6(15%) with partial remission(PR), respectively. And 2 cases were CR after double transplantation. Median follow-up time was 28.4 (3.1 to 88) months,15 cases presented disease progression, 7 cases were dead, 3-year estimated progression-free survival(PFS) and overall survival(OS) rate were 45.1% and 82% respectively. Unvariate analysis showed that the OS was affected by ISS stage (P<0.05), CR and VGPR (P<0.05) after transplantation; PFS was affected by ISS stage (P<0.01), before transplantation induction therapy (27 cases with bortezomizomi or thalidomide) (P<0.05), disease risk stratification (6 cases in high risk group) (P<0.05) , CR and VGPR (P<0.05) before transplantation, CR and VGPR (P<0.01) after transplantation. Cox multivariate regression analysis showed that the independent prognostic factors for OS were ISS stage, CR and VGPR after transplantation; the independent prognostic factors for PFS were the CR, VGPR, ISS stage after transplantation and induction therapy before transplant., Conclusion: Auto-HSCT can improve the clinical efficacy and survival rate of MM patients; ISS stage, CR and VGPR after transplantation are independent prognostic factors for OS and PFS, and induction therapy before transplantation is also an independent prognostic factor for PFS.

Objective: To investigate the effect of ATO on the proportion of Treg in the peripheral blood of patients with severe aplastic anemia (SAA) in vitro., Methods: The peripheral blood of 20 newlydiagnosed patients were collected, and the peripheral blood monomuclear cells (PBMNC) were extracted. After the PBMNC were treated with ATO of different concentrotions (0, 1, 2.5 and 5 µmol/L) for 96 hours, the proportion of CD44 + CD25 + CD127 low regulatatory T cells (Treg) were detected by flow cytometry. The expression levels of Foxp3 mRNA were detected by RT-PCR, and the levels of IFN-γ,IL-4,IL-17 and TGF-β1 were detected by ELTSA to verify the results of flow cytomery., Results: ATO significantly increased the proportion of Treg (P<0.01) at the concentration of 2.5 and 5 µmol/L, and the rising degree of Treg proportion improved with the increasing ATO concentration(r= 0.524). Treg proportion increased at a concentration of 1 µmol/L, but without statistical significance (P>0.05). At 1(P<0.05), 2.5(P<0.01) and 5 µmol/L(P<0.01), ATO significantly up-regulated the expression of Foxp3 mRNA, and the increase of Foxp3 mRNA positively and linearly correlated with the increase of Treg cell-frequency(r=0.523). ATO significantly reduced the levels of IFN-γ (at ATO 1,2.5 and 5 µmol/L, P<0.01), IL-4 (at ATO 2.5 µmol/L, P<0.01; at ATO 5 µmol/L, P<0.01) and IL-17(at ATO 2.5 µmol/L, P<0.05; at ATO 5 µmol/L, P<0.01). ATO had no significant effect on TGF-β1 at 1(P>0.05) and 2.5 µmol/L (P>0.05), but significantly reduced TGF-β1 level at 5 µmol/L (P<0.05)., Conclusion: ATO can mediate the immune regulation through up-regulating the proportion of Treg in peripheral blood of patients with SAA and reducing the levels of IFN-γ, IL-4 and IL-17.

Objective: In 2018, the American Heart Association/American Stroke Association (AHA/ASA) has developed the latest 2018 guidelines for the early management of patients with acute ischemic stroke (AIS), based on the latest evidences. The 2018 guidelines including recommendations on pre-hospital and in-hospital management treatment, has revised and add new recommendations from 2013 guideline. The major changes in 2018 guideline involve applications of brain imaging in early stage, intravenous thrombolysis and mechanical thrombectomy, et al. This review interprets the 2018 guidelines for clinicians to improve the clinical diagnosis, treatment and outcome of patients with AIS.

To explore the efficacy and influencing factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myeloid leukemia and granulocytic sarcoma (GS). Clinical outcome including hematopoietic reconstitution, transplant-related complications, survival and relapse were collected and retrospectively analyzed in 9 patients with myeloid leukemia and GS after allo-HSCT. Hematopoiesis reconstitution was achieved in all the 9 recipients. Four cases developed acute graft-versus-host disease (GVHD), and 1 with chronic GVHD. The median follow-up time after transplantation was 10(4-81) months. Only 2 cases survived, the other 7 died of relapse. The median time of relapse after transplantation was 5(3-19) months. Allo-HSCT is relatively effective treatment for patients with myeloid leukemia and GS. Relapse after transplantation remains the major factor of mortality.

Objective: To evaluate the efficacy of unrelated donor allogeneic hematopoietic stem cell transplantation(URD allo-HSCT) for children and adolescents with severe aplastic anemia (SAA). Methods: Clinical data of 34 SAA children and adolescents undergoing allo-HSCT were retrospectively analyzed from October 2001 to October 2015. According to the source of donor, the patients were divided into matched sibling donor allo-HSCT group (MSD group) and unrelated donor group (URD group). The clinical outcome of SAA children and adolescents receiving URD allo-HSCT was assessed, and patients in MSD allo-HSCT group were enrolled as control at the same period. Results: The rate of hematopoietic reconstitution, the time of neutrophil and platelet engraftment, incidence of chimerism and graft rejection between two groups were not statistically different.The incidence of acute graft-versus-host disease (GVHD) in URD group was significantly higher than that in MSD group [42.9%(6/14) vs 10.5%(2/19), P =0.047]. The incidence of grade Ⅱ-Ⅳ acute GVHD and chronic GVHD in URD were higher than those in MSD group [21.4%(3/14) vs 5.3%(1/19), P =0.288; 35.7%(5/14) vs 5.3%(1/19), P =0.062, respectively], yet without significant difference between two groups. Other transplant-related complications including pulmonary complications, hemorrhagic cystitis, incidence of EBV and CMV reactivation and venous occlusive disease were comparable with two regimens. Estimated 5-years overall survival (OS) rate and disease free survival (DFS) rate were not statistically significant between URD group and MSD group [(84.4±6.6)% vs (89.4±7.1)%, (82.5±5.4)% vs (82.1±4.3)%; P =0.766, P =0.884, respectively]. Conclusions: By multivariate analysis, the outcome of URD allo-HSCT in SAA children and adolescent is similar to MSD allo-HSCT. It could be an alternative option as the first-line treatment for SAA children and adolescents without HLA matched sibling donors.

Objective: To study the effect of emodin on protein and gene expressions of the massagers in mobility signal transduction system of cholecyst smooth muscle cells in guinea pig with cholesterol calculus., Methods: The guinea pigs were randomly divided into 4 groups, such as control group, gall-stone (GS) group, emodin group and ursodeoxycholic acid (UA) group. Cholesterol calculus models were induced in guinea pigs of GS, emodin and UA groups by lithogenic diet, while emodin or UA were given to the corresponding group for 7 weeks. The histomorphological and ultrastructure change of gallbladder were detected by microscope and electron microscope, the content of plasma cholecystokinin (CCK) and [Ca 2+ ] i were analyzed successively by radioimmunoassay and flow cytometry. The protein and mRNA of Gsα, Giα and Cap in cholecyst cells were determined by western blotting and real time polymerase chain reaction (RT-PCR)., Results: Emodin or UA can relieve pathogenic changes in epithelial cells and muscle cells in gallbladder of guinea pig with cholesterol calculus by microscope and transmission electron microscope. In the cholecyst cells of GS group, CCK levels in plasma and [Ca 2+ ] i decreased, the protein and mRNA of GS were down-regulated, the protein and mRNA of Gi and Cap were up-regulated. Emodin significantly decreased the formative rate of gallstone, improved the pathogenic change in epithelial cells and muscle cells, increased CCK levels in plasma and [Ca 2+ ] i in cholecyst cells, enhanced the protein and mRNA of Gs in cholecyst cells, reduced the protein and mRNA of Gi and Cap in cholecyst cells in guinea pig with cholesterol calculus., Conclusion: The dysfunction of gallbladder contraction gives rise to the disorders of mobility signal transduction system in cholecyst smooth muscle cells, including low content of plasma CCK and [Ca 2+ ] i in cholecyst cells, abnormal protein and mRNA of Gs, Gi and Cap. Emodin can enhance the contractibility of gallbladder and alleviate cholestasis by regulating plasma CCK levels, [Ca 2+ ] i in cholecyst cells and the protein and mRNA of Gs, Gi and Cap., (Copyright © 2016 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.)

Objective: To study the mechanism of insulin resistance in the cholesterol gallstone formation from insulin signal transduction pathway so as to reveal the possible mechanism and the effective role of Albiflorin Granule on preventing the cholesterol gallstones., Methods: Serum triglycerides (TG), free fatty acid (FFA), and total cholesterol (TC) from different groups were measured and liver cells InsR, PKB, IKK-β protein expression levels were detected by western blotting., Results: Albiflorin significantly decreased the cholesterol gallstone formation rate, increased glucose infusion rate in gallstone guinea pigs and improved insulin resistance. Compared with the normal group, insulin receptor and PKB protein expression in GS group were significantly reduced. IKK-β protein in the GS group increased significantly and Albiflorin could reduce IKK-β protein expression in guinea pig liver cells., Conclusions: The model of insulin resistance in cholesterol gallstone guinea pig was successfully established, which plays an important role in the cholesterol gallstone formation. All aspects of insulin signaling pathway are involved in gallstone formation. Albiflorin can regulate various aspects of insulin signal transduction pathway to prevent the formation of gallbladder., (Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.)

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo- HSCT) for patients with severe aplastic anemia (SAA)., Methods: A retrospective study was conducted in 41 SAA patients received allo-HSCT from Oct. 2001 to May 2015. There were 27 males and 14 females with median age of 17(2-43) years old. Of them, 24 received matched sibling donor HSCT, 17 received unrelated donor transplantation., Results: Hematopoiesis reconstitution was achieved in 38 patients (92.68%). Median time of neutrophils and platelets implantation was 16(10-57) d and 20(9-83) d in evaluable patients, respectively. Acute GVHD occurred in 13 cases, chronic GVHD in 8 cases, and graft rejection in 5 cases. Median follow-up time was 27(3- 154) months. The prospective OS for 3 years was (75.1±8.3)%. Transplantation related mortality was 24.39% (10 cases). Multivariate analysis revealed that grade Ⅱ -Ⅳ aGVHD [P=0.018, OR=27.481 (95% CI 2.377-392.636) ] and invasive fungal disease [P=0.021, OR=21.364 (95% CI 1.732- 354.185) ] were independent risk factors of OS for SAA patients after allo- HSCT., Conclusion: Allo- HSCT is an efficient and safe therapy for the patients with SAA, not only for patients with HLA matched sibling donor, but also for those with only HLA matched unrelated donor available. Grade Ⅱ- Ⅳ aGVHD and invasive fungal disease were associated with lower OS rate.

Objective: To investigate the distribution of pathogens and drug resistance in bile and the association between the pregnane X receptor (PXR) gene polymorphisms, traditional Chinese medicine (TCM) syndromes and the risk of cholesterol gallstone disease (CGD)., Methods: A total of 392 samples were enrolled in this study from January 2014 to February 2015, among which 192 patients were with CGD, and 200 samples were healthy. Strains were isolated and susceptibility testing was the disk diffusion method susceptibility testing. The patients were divided into hepatochlic hygropyrexia, stagnation of liver-qi, and the accumulation of damp. The PXR gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. The association between the PXR gene polymorphisms and the risk of CGD was examined by logistic regression analysis., Results: A total of 192 cases were detected in 230 of bile culture pathogens, including Gram-negative bacteria 133 (57.83%), Gram-positive bacteria 76 (33.04%), and fungi 21 (9.13%). The top five pathogens were Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Candida albicans, and Enterococcus feces, of which 110 cases was of single infection, 48 cases of mixed infection of two strains, eight cases of mixed infection of three bacteria. Among 59 Escherichia coli, the yield extended-spectrum beta-lactamases had 40 (67.80%). The hepatochlic hygropyrexia was the most TCM syndrome, followed by stagnation of liver-qi, and the accumulation of damp was least. Different pathogens and the rs6785049 genotypes distributed differently in cholelithiasis patients with different TCM syndromes (P < 0.05). In hepatochlic hygropyrexia patients the Gram-negative bacteria was most. There was significant differences between CGD group and control group in rs6785049 (P < 0.001). Comparison with wild-type portable GG, GA genotype increased the risk of the occurrence of gallstones (OR = 0.40, 95%CI: 0.16-0.79); likewise, carrying the GA+AA genotype also increased the risk (OR = 0.38, 95%CI: 0.19-0.81). There was no significant differences in rs2276707, rs3814055 site polymorphic loci alleles in CGD group and control group., Conclusions: In the treatment of cholelithiasis, bile samples should be collected for bacterial culture and sensitivity test, and drugs should be strictly chosen based on the results. The rs6785049 polymorphisms in PXR gene may increase the risk of gallstones ontogeny, and gallstones can be early detected and prevented by detecting genotypes. rs6785049 polymorphisms in PXR gene may has relationship with TCM syndromes., (Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.)

Objective: To evaluate the efficiency and safety of rituximab and dexamethasone combined with cyclophosphamide for treating patients with relapsed and refractory immune thrombocytopenia (ITP)., Methods: Twelve patients with relapsed and refractory immune thrombocytopenia were prospectively enrolled in this study, and received rituximab 375 mg/m(2) once a week for 4 weeks, dexamethasone 40 mg once a day for consecutive 4 days, and cyclophosphamide 500 mg/m(2) biweekly for 2 weeks. The levels of IFN-r and IL-4 in peripheral blood of patients were measured by enzyme-linked immunosorbent assay (ELISA), and the percentages of Breg, Treg and Th17 cells were detected by flow cytometry before and after treatment. Efficiency was evaluated according to platelet counts, and side effects were observed., Results: Six out of 12 patients reached to complete remission and 4 patients reached to partial remission, with the total response rate 83.33%. The platelet counts [(115.42 ± 76.60) × 10(9)/L] after treatment were significantly higher than that before treatment [(115.42 ± 76.60) × 10(9)/L] (P < 0.001). The ratio of IFN-r/ IL4 after treatment (5.89 ± 2.30) was very significantly lower than that before treatment (7.00 ± 2.73) (P = 0.002). The percentage of Breg cells after treatment [(21.27 ± 4.28)%] were much significantly higher than that before treatment [(15.48 ± 1.67)%] (P < 0.001). The ratio of Treg/Th17 after treatment (3.07 ± 1.50) was significantly higher than that before treatment (0.98 ± 0.45) (P < 0.001). Infusion reaction was observed in 1 patient, secondary hypertension and hyperglycemia were in 1 patient, and pneumonia in 2 patients., Conclusion: Rituximab and dexamethasone combined with cyclophosphamide can improve the outcomes of patients with relapsed and refractory immune thrombocytopenia patients and they were well tolerated, its mechanism may be related with the balance between T cell sunsets and Treg cells.