Single-Dose Rifapentine in Household Contacts of Patients with Leprosy.

BACKGROUND: Previous studies have suggested that a single dose of rifampin has protective effects against leprosy in close contacts of patients with the disease. Rifapentine was shown to have greater bactericidal activity against Mycobacterium leprae than rifampin in murine models of leprosy, but data regarding its effectiveness in preventing leprosy are lacking. METHODS: We conducted a cluster-randomized, controlled trial to investigate whether single-dose rifapentine is effective in preventing leprosy in household contacts of patients with leprosy. The clusters (counties or districts in Southwest China) were assigned to one of three trial groups: single-dose rifapentine, single-dose rifampin, or control (no intervention). The primary outcome was the 4-year cumulative incidence of leprosy among household contacts. RESULTS: A total of 207 clusters comprising 7450 household contacts underwent randomization; 68 clusters (2331 household contacts) were assigned to the rifapentine group, 71 (2760) to the rifampin group, and 68 (2359) to the control group. A total of 24 new cases of leprosy occurred over the 4-year follow-up, for a cumulative incidence of 0.09% (95% confidence interval [CI], 0.02 to 0.34) with rifapentine (2 cases), 0.33% (95% CI, 0.17 to 0.63) with rifampin (9 cases), and 0.55% (95% CI, 0.32 to 0.95) with no intervention (13 cases). In an intention-to-treat analysis, the cumulative incidence in the rifapentine group was 84% lower than that in the control group (cumulative incidence ratio, 0.16; multiplicity-adjusted 95% CI, 0.03 to 0.87; P = 0.02); the cumulative incidence did not differ significantly between the rifampin group and the control group (cumulative incidence ratio, 0.59; multiplicity-adjusted 95% CI, 0.22 to 1.57; P = 0.23). In a per-protocol analysis, the cumulative incidence was 0.05% with rifapentine, 0.19% with rifampin, and 0.63% with no intervention. No severe adverse events were observed. CONCLUSIONS: The incidence of leprosy among household contacts over 4 years was lower with single-dose rifapentine than with no intervention. (Funded by the Ministry of Health of China and the Chinese Academy of Medical Sciences; Chinese Clinical Trial Registry number, ChiCTR-IPR-15007075.).

Exenatide reduces atrial fibrillation susceptibility by inhibiting hKv1.5 and hNav1.5 channels.

Exenatide, a promising cardioprotective agent, protects against cardiac structural remodeling and diastolic dysfunction. Combined blockade of sodium and potassium channels is valuable for managing atrial fibrillation (AF). Here, we explored whether exenatide displayed anti-AF effects by inhibiting human Kv1.5 and Nav1.5 channels. We used the whole-cell patch-clamp technique to investigate the effects of exenatide on hKv1.5 and hNav1.5 channels expressed in human embryonic kidney 293 cells and studied the effects of exenatide on action potential (AP) and other cardiac ionic currents in rat atrial myocytes. Additionally, an electrical mapping system was used to explore the effects of exenatide on electrical properties and AF activity in isolated rat hearts. Finally, a rat AF model, established using acetylcholine and calcium chloride, was employed to evaluate the anti-AF potential of exenatide in rats. Exenatide reversibly suppressed IKv1.5 with IC50 of 3.08 µM, preferentially blocked the hKv1.5 channel in its closed state, and positively shifted the voltage-dependent activation curve. Exenatide also reversibly inhibited INav1.5 with IC50 of 3.30 µM, negatively shifted the voltage-dependent inactivation curve, and slowed its recovery from inactivation with significant use-dependency at 5 and 10 Hz. Furthermore, exenatide prolonged AP duration and suppressed the sustained K+ current (Iss) and transient outward K+ current (Ito), but without inhibition of L-type Ca2+ current (ICa,L) in rat atrial myocytes. Exenatide prevented AF incidence and duration in rat hearts and rats. These findings demonstrate that exenatide inhibits IKv1.5 and INav1.5in vitro and reduces AF susceptibility in isolated rat hearts and rats.

KN-93 promotes HDAC4 nucleus translocation to promote fatty acid oxidation in myocardial infarction.

Myocardial infarction (MI) is a potentially fatal disease that causes a significant number of deaths worldwide. The strategy of increasing fatty acid oxidation in myocytes is considered a therapeutic avenue to accelerate metabolism to meet energy demands. We conducted the study aiming to investigate the effect of KN-93, which induces histone deacetylase (HDAC)4 shuttling to the nucleus, on fatty acid oxidation and the expression of related genes. A mouse model of myocardial infarction was induced by isoprenaline administration. Heart damage was assessed by the detection of cardiac injury markers. The level of fatty acid oxidation level was evaluated by testing the expression of related genes. Both immunofluorescence and immunoblotting in the cytosol or nucleus were utilized to observe the distribution of HDAC4. The interaction between HDAC4 and specificity protein (SP)1 was confirmed by co-immunoprecipitation. The acetylation level of SP1 was tested after KN-93 treatment and HDAC4 inhibitor. Oxygen consumption rate and immunoblotting experiments were used to determine whether the effect of KN-93 on increasing fatty acid oxidation is through HDAC4 and SP1. Administration of KN-93 significantly reduced cardiac injury in myocardial infarction and promoted fatty acid oxidation both in vitro and in vivo. KN-93 was shown to mediate nuclear translocation of HDAC4. HDAC4 was found to interact with SP1 and reduce SP1 acetylation. HDAC4 or SP1 inhibitors attenuated the effect of KN-93 on fatty acid oxidation. In conclusion, KN-93 promotes HDAC4 translocation to the nucleus, thereby potentially enhancing fatty acid oxidation by SP1.

A water quality assessment model involving novel fluorescence technology.

The reasonable utilization of water resources and real-time monitoring of water pollution are the core tasks of current world hydrological and water conservancy work. Novel technologies and methods for monitoring water pollution are important means to ensure water health. However, the absence of intuitive and simple analysis methods for the assessment of regional pollution in large-scale water bodies has prevented scientists from quickly grasping the overall situation of water pollution. In this study, we propose a strategy based on the unique combination of fluorescence technology and simple kriging (SK) interpolation (FL-SK) for the first time. This strategy could present the relative magnitude and distribution of the physicochemical indicators of a whole natural lake intuitively and accurately. The unique FL-SK model firstly offers a simple and effective water quality method that provides the pollution index of different sampling points in lakes. The macroscopic evaluation of large-scale water bodies by the FL-SK model primarily relies on the fluorescence response of the RDM-TPE to the comprehensive indicators of the water body, as experimental results have revealed a good correlation between fluorescent responses and six normalized physicochemical indicators. Multiple linear regression and fluorescence response experiments on RDM-TPE indicate that to some extent, the fluorescence signals of the FL-SK model may originate from a certain type of sulfide in the water body. Pattern discovery could enable the analysis of pollution levels in other ecosystems and promote early pollution assessment in the future.

Whole-exome sequencing identifies FANC heterozygous germline mutation as an adverse factor for immunosuppressive therapy in Chinese aplastic anemia patients aged 40 or younger: a single-center retrospective study.

Acquired aplastic anemia (AA) is a bone marrow failure disorder characterized by pancytopenia, and immunosuppressive therapy (IST) is the optional first-line management. Several studies identified the influencing factors on IST response; however, there are still a considerable number of patients suffering from poor prognoses. In this study, we enrolled 61 AA patients aged ≤ 40 years old, and whole-exome sequencing (WES) found unexpected high FANC heterozygous germline mutations (28/61, 45.9%). Patients with FANC mutations have a significantly lower absolute reticulocyte count and CD34+ % in the bone marrow and also lower 3-, 6-, and 9-month IST response than that without mutation, which were 0% vs. 25% (P = 0.017), 26.3% vs. 42.1% (P = 0.495), and 29.4% vs. 72.2% (P = 0.011), especially in anti-thymocyte globulin combined with the cyclosporin A (ATG + CsA) group, which were 0% vs.33.4% (P = 0.143), 25% vs.83.3% (P = 0.103), and 25% vs. 100% (P = 0.003), respectively. The event-free survival in the FANCwt group was also better than that in the FANCmut group (P = 0.016) and also showed in patients who received ATG + CsA treatment (P = 0.045). In addition, all the adverse effects of FANC germline mutation were not significant in stem cell-transplanted group. Our result indicated that the WES-based detection of FANC heterozygous germline mutations may have a great meaning in predicting IST response of acquired AA. This study was registered at chictr.org.cn (# ChiCTR2100054992).

Assessing the pollution level of a subtropical lake by using a novel hydrogen sulfide fluorescence technology.

Hydrogen sulfide (H2S) is an important environmental toxin with bi-directional biological effects on organisms. In natural waters, H2S complexes with heavy metal ions in an anaerobic environment influence heavy metals' bioavailability and induce phosphorus release and eutrophication in water columns. Traditional detection techniques, such as colorimetric, electrochemical, and chromatographic, cannot simultaneously detect H2S and pollution assessment of subtropical lakes. To address these technical defects, we developed small-molecule fluorescent probes to evaluate the pollution level in natural water bodies. This method relies on the combination of the probes' response signals to raw water and the water quality index, thereby enhancing the accuracy and reliability of water quality assessments. Furthermore, this novel material has a large Stokes shift. It can detect complex levels of H2S concentrations in natural water bodies by correlating the degree of contamination and fluorescence signals. The development of this visual research tool for detecting environmental H2S levels in natural water bodies is expected to have meaningful, practical applications.

Icariin protects bone marrow mesenchymal stem cells in aplastic anemia by targeting MAPK pathway.

BACKGROUND: Icariin, the main pharmacological active flavonoid extracted from Epimedi herba, can regulate cellular processes in diverse diseases. The aim of this study was to explore the effects and mechanisms of icariin on proliferation and adipogenesis of bone marrow mesenchymal stem cells (BMSCs) in aplastic anemia (AA). METHODS AND RESULTS: Bone marrow mesenchymal stem cells were isolated from posterior tibias and femurs of AA rats that were induced by benzene and cyclophosphamide and gavaged with icariin. The isolated BMSCs were characterized morphologically and immunologically by positive markers (CD29 and CD90) and negative markers (CD34 and CD45). CCK-8 assay was performed to examine the BMSCs proliferation. Cell apoptosis and cell cycle were detected by flow cytometry. Oil red O staining was carried out to evaluate the adipogenesis of BMSCs. The mRNA expression of PPARγ, C/EBP-α, and FABP4 was measured by qRT-PCR. The protein levels of p-p38/p38, p-JNK/JNK, p-ERK/ERK, PPARγ, C/EBP-α, and FABP4 were detected using Western blotting. Icariin promoted the proliferation of BMSCs from AA rats in a dose-dependent manner. The protein levels of p-p38/p38, p-JNK/JNK, and p-ERK/ERK were downregulated in BMSCs from AA rats after icariin treatment. Icariin inhibited the apoptosis and arrested cell cycle at G/S phase of BMSCs from AA rats. The adipogenesis of BMSCs from AA rats was also suppressed after icariin treatment. However, the effects of icariin on BMSCs were weakened by p38 agonist addition. CONCLUSIONS: Icariin promoted the proliferation and inhibited the apoptosis and adipogenesis of BMSCs in AA by suppressing MAPK pathway.

GM-CSF enhanced the effect of CHOP and R-CHOP on inhibiting diffuse large B-cell lymphoma progression via influencing the macrophage polarization.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a common type of the Non-Hodgkin lymphomas (NHLs) formed by the neoplastic transformation of mature B cells. As the first-line therapeutics, CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy and R-CHOP (Rituximab + CHOP), either using alone or in combination with GM-CSF, have achieved great efficacy in DLBCL patients. However, the underlying mechanisms are still largely unknown. METHODS: In the present study, the combination use of CHOP and R-CHOP with GM-CSF was used to evaluate their effects on the tumor immune microenvironment of DLBCL. CHOP and R-CHOP administration was found to inhibit the growth and metastasis of DLBCL, with a higher efficacy in R-CHOP-challenged DLBCL mice. The anti-tumor effect of CHOP and R-CHOP was further amplified by GM-CSF. RESULTS: CHOP and R-CHOP therapeutics potentiated the anti-tumor properties of macrophages, as evidenced by the increased M1 macrophage and the decreased M2 macrophage accumulation in DLBCL-bearing mice. In a co-culture system, macrophages primed with CHOP and R-CHOP therapeutics inhibited multiple malignant behaviors of DLCBL cells. Mechanistically, CHOP/R-CHOP suppressed the activation of AKT signaling. These anti-tumor effects of CHOP/R-CHOP were all augmented by GM-CSF. CONCLUSIONS: Our work provided new insights into the immune-regulatory roles of CHOP and R-CHOP in the treatment of DLBCL, as well as the synergistic effects of GM-CSF in CHOP and R-CHOP therapeutics. Although our results suggest the synergistic effect of GM-CSF on DLBCL already sensitive to CHOP and R-CHOP, however, future studies are warranted to explore the role of GM-CSF on R-CHOP-resistant DLBCL. Trial registration Not applicable.

Iron overload adversely effects bone marrow haematogenesis via SIRT-SOD2-mROS in a process ameliorated by curcumin.

BACKGROUND: Iron overload, which is common in patients with haematological disorders, is known to have a suppressive effect on haematogenesis. However, the mechanism for this effect is still unclear. The antioxidant curcumin has been reported to protect against iron overload-induced bone marrow damage through an as-yet-unknown mechanism. METHODS: We established iron overload cell and mouse models. Mitochondrial reactive oxygen species (mROS) levels, autophagy levels and the SIRT3/SOD2 pathway were examined in the models and in the bone marrow of patients with iron overload. RESULTS: Iron overload was shown to depress haematogenesis and induce mitochondrion-derived superoxide anion-dependent autophagic cell death. Iron loading decreased SIRT3 protein expression, promoted an increase in SOD2, and led to the elevation of mROS. Overexpression of SIRT3 reversed these effects. Curcumin treatment ameliorated peripheral blood cells generation, enhanced SIRT3 activity, decreased SOD2 acetylation, inhibited mROS production, and suppressed iron loading-induced autophagy. CONCLUSIONS: Our results suggest that curcumin exerts a protective effect on bone marrow by reducing mROS-stimulated autophagic cell death in a manner dependent on the SIRT3/SOD2 pathway.

Identification of berberine as a novel drug for the treatment of multiple myeloma via targeting UHRF1.

BACKGROUND: Current therapies for multiple myeloma (MM) are associated with toxicity and resistance, highlighting the need for novel effective therapeutics. Berberine (BBR), a botanical alkaloid derived from several Berberis medicinal plants, has exhibited anti-tumor effects, including against multiple myeloma (MM); however, the molecular mechanism underlying the anti-MM effect has not been previously described. This study aimed to identify the target of berberine and related mechanisms involved in its therapeutic activity against MM. RESULTS: Here, we demonstrated that BBR treatment killed MM cells in vitro and prolonged the survival of mice bearing MM xenografts in vivo. A screening approach integrating surface plasmon resonance (SPR) with liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified UHRF1 (ubiquitin-like with PHD and RING Finger domains 1) as a potential target of BBR. Combining molecular docking and SPR analysis, we confirmed UHRF1 as a BBR-binding protein and discovered that BBR binds UHRF1 in the tandem tudor domain and plant homeodomain (TTD-PHD domain). BBR treatment induced UHRF1 degradation via the ubiquitin-dependent proteasome system and reactivated p16INK4A and p73 in MM cells. Overexpression of UHRF1 promoted the MM cell proliferation and rendered MM cells more resistant to BBR, while silencing of UHRF1 with siRNA attenuated BBR-induced cytotoxicity. CONCLUSIONS: In summary, our study has identified UHRF1 as a direct target of BBR and uncovered molecular mechanisms involved in the anti-MM activity of BBR. Targeting UHRF1 through BBR may be a novel therapeutic strategy against MM.

The regulatory roles of VEGF-Notch signaling pathway on aplastic anemia with kidney deficiency and blood stasis.

OBJECTIVE: Vascular endothelial growth factor (VEGF)-Notch signaling pathway plays an important role in aplastic anemia (AA). This study aimed to evaluate the regulatory roles of VEGF-Notch signaling pathway on mesenchymal stem cells (MSCs) isolated from AA patients with kidney deficiency and blood stasis (KB) (AA MSCs). METHODS: Expression of VEGF-Notch signaling related factors, including VEGF, VEGFR, Notch-1, Jagged1, Delta-like1, and hes1 was detected in bone marrow (BM) tissues and AA MSCs by Western blot analysis. VEGF (100 ng/mL) and γ-secretase inhibitor (DAPT) (10 µM) was used to active and inhibit VEGF-Notch signaling in AA MSCs, respectively. After treatment, the proliferation, apoptosis, and adipogenic differentiation of AA MSCs was detected by Cell Counting Kit-8, flow cytometry, and Oil red O staining, respectively. Lentivirus short hairpin RNA (shRNA) were constructed to downregulate Notch-1 and VEGF in normal bone marrow mesenchymal stem cells (BMSCs), and the effects of VEGF/Notch-1 shRNA transfected BMSCs on the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs) were evaluated. RESULTS: Significantly lower expression of VEGF, VEGFR, Notch-1, Jagged1, Delta-like1, and hes1 was revealed in AA BM tissues and AA MSCs when compared with the normal control (P < 0.05). The intervention of DAPT significantly inhibited the proliferation, and promoted the apoptosis and adipogenic differentiation of AA MSCs, while VEGF intervention exhibited opposite results (P < 0.05). Meanwhile, the proliferation, migration, and angiogenesis of HUVECs were significantly promoted by normal BMSCs, while inhibited by VEGF/Notch-1 shRNA transfected BMSCs (P < 0.05). CONCLUSION: The activation of VEGF-Notch signaling pathway may be a potential therapeutic target for AA with KB.

Identification of the UBA2-WTIP fusion gene in acute myeloid leukemia.

Identifying and targeting oncogenic fusion genes have revolutionized the treatment of leukemia, such as PML-RARα fusion gene in acute promyelocytic leukemia. Here we identified an intrachromosomal fusion gene located on chromosome 19q.13 between UBA2 and WTIP gene in a case of acute myeloid leukemia. The UBA2-WTIP fusion gene contains the N-terminal E1_enzyme_family, VAE_Ubl domains of UBA2, and the C-terminal LIM domains of WTIP. The UBA2-WTIP fusion was detected by reverse transcriptase polymerase chain reaction and Sanger sequencing in 19 of 56 acute myeloid leukemia samples (33.9%). Ectopic expression of the UBA2-WTIP fusion in human acute myeloid leukemia KG-1a cells showed enhanced cell proliferation both in vitro and in vivo. The UBA2-WTIP fusion induced phosphorylation of STAT3, STAT5 and ERK1/2, and abrogates WTIP-mediated mammalian processing body formation. Finally, triptolide displayed selective cytotoxicity against KG-1a cells harboring the UBA2-WTIP fusion. Collectively, our findings suggest that the UBA2-WTIP fusion is an oncogenic fusion gene, as well as a promising therapeutic target for the treatment of acute myeloid leukemia.

Integrative analysis of signaling pathways and diseases associated with the miR-106b/25 cluster and their function study in berberine-induced multiple myeloma cells.

Berberine (BBR), a traditional Chinese herbal medicine compound, has emerged as a novel class of anti-tumor agent. Our previous microRNA (miRNA) microarray demonstrated that miR-106b/25 was significantly down-regulated in BBR-treated multiple myeloma (MM) cells. Here, systematic integration showed that miR-106b/25 cluster is involved in multiple cancer-related signaling pathways and tumorigenesis. MiREnvironment database revealed that multiple environmental factors (drug, ionizing radiation, hypoxia) affected the miR-106b/25 cluster expression. By targeting the seed region in the miRNA, tiny anti-mir106b/25 cluster (t-anti-mir106b/25 cluster) significantly induced suppression in cell viability and colony formation. Western blot validated that t-anti-miR-106b/25 cluster effectively inhibited the expression of P38 MAPK and phospho-P38 MAPK in MM cells. These findings indicated the miR-106b/25 cluster functioned as oncogene and might provide a novel molecular insight into MM.

Clinical features of relapse after multidrug therapy for leprosy in China.

BACKGROUND: Although the World Health Organization (WHO) has defined relapse in leprosy, it is often difficult to confirm a relapse, especially in paucibacillary (PB) patients. OBJECTIVE: To study features of relapse cases in order to determine the information needed to allow better management of relapses in the leprosy control programme. DESIGN: A retrospective survey by questionnaire was carried out at national level at the end of 2012. RESULTS: There were 40 relapsed patients on register. The clinical form of leprosy was TT5, BT4, BB5, BL13 and LL13. Twenty-eight patients had had a positive skin smear test at the start of MDT, with a BI ranging from 0.83 to 6.0. At the time of completing MDT, the skin smear test remained positive in seven patients. After completion of MDT, other family members of 13 patients were identified as new leprosy patients. All relapse cases showed one or more active skin lesions. There were 33 patients with a positive skin smear test at the time of relapse. A total of 23 patients had a biopsy at the time of relapse, including seven patients with a negative skin smear test. The histological features of relapsed BB-LL patients included granulomas containing macrophages or epithelioid cells with sparse lymphocytes and acid-fast bacilli. The histological features of seven patients with negative skin smears showed epithelioid cell granulomas with dense lymphocytes surrounding the granuloma, but without distinct edema in the dermis. The average interval from completion of MDT to the diagnosis of relapse was 168.5 ± 92.6 months with a range of 21-322 months. During the study, nine patients were tested for rifampicin resistance, but none showed any mutation. CONCLUSIONS: Leprosy relapse after MDT usually occurred late and all relapse cases had new active skin lesions. Most patients relapsed with a positive skin smear after previously reaching negative BI status. Relapse with a negative skin smear test should be confirmed very cautiously.

Survey on child leprosy patients and problems resulted from the disease in China.

OBJECTIVES: To understand the situation of child leprosy patients in the low prevalence situation pertaining in China. METHOD: A retrospective survey by questionnaire was carried out in all 32 provinces of mainland of China in 2011. All data concerning child cases detected from January 2005 to December 2009 were collected by professional health workers working at county level. RESULTS: During the study, only 165 questionnaires were collected for analysis. Among 165 child cases, 96 were boys, 69 were girls with an average age of 11-7 years old. 80% of child cases were members of families with other leprosy affected people. 145 (85%) child cases took their MDT secretly (nobody outside the family knew the child suffered from leprosy), and three (1.8%) children died, one each from dapsone syndrome, suicide and severe pneumonia. During follow-up, four child cases developed new disability increasing the Grade 2 disability rate to 13.3% (22/165). At end of the study, 8.2% of children had discontinued their study at school, and 7.5% had moved to a remote place to do casual work, while 6.3% stayed at home. 31% of child patients thought that leprosy caused a negative impact on their daily life. Two children had a hostile attitude toward society due to the stigma caused by leprosy. CONCLUSIONS: In both high and low endemic areas, as long as there is an infectious source of leprosy in the family, there is a possibility for children to develop leprosy. Contact surveys should be done to detect early disease, especially when there are children in the household.

[Treatment of myelodysplastic syndrome by hematopoietic stem cell transplantation combined with Chinese medical syndrome typing: a clinical study].

OBJECTIVE: To evaluate the clinical efficacy of treating myelodysplastic syndrome (MDS) by hematopoietic stem cell transplantation (HSCT) combined with Chinese medical syndrome typing. METHODS: From July 2009 to July 2013, 6 MDS patients were treated with allo-HSCT combined with Chinese medical syndrome typing from HLA-identical sibling donors at Department of Hematology, Zhejiang Provincial Hospital of Chinese Medicine. Patients were classified as refractory anemia (RA, 2 cases), refractory anemia with ringed sideroblast (RARS, 1 case), refractory cytopenia with multilineage dysplasia (RCMD, 2 cases), and RA with excess blasts-I (RAEB-I , 1 case). Modified BuCy conditioning regimen was used in all 6 cases. Two patients received bone marrow transplantation (BMT), 1 patient received peripheral blood stem cell transplantation (PBSCT), and 3 patients received BMT + PBSCT. In order to prevent the occurrence of graft-versus-host disease (GVHD), all patients were treated with cyclosporine + methotrexate + mycophenolate mofetil. Different Chinese medical treatment methods (by syndrome typing) were given to patients according to different criticality of international prognostic scoring system (IPSS, 5 at moderate risk and 1 at high risk). RESULTS: All 6 patients successfully reconstructed their hematopoietic system. The time from transplantation to ANC ≥ 0.5 x 10(9)/L and platelet (PLT) ≥ 20 x10(9)/L were 13 (9-15) days and 11 (9-22) days respectively. Main complications were GVHD. Acute GVHD (aGVHD) occurred in 4 cases, 3 cases of grade I and 1 case of grade II, and local chronic GVHD (cGVHD) occurred in 1 patient. All cases survived with median follow-up of 18 (11-58) months. The overall survival (OS) and disease-free survival (DFS) rate were 100%. CONCLUSIONS: HSCT combined with Chinese medical syndrome typing could improve clinical symptoms, reduce transplant as- sociated complications. So it was an effective treatment choice for MDS.

A rare case of daratumumab-associated encephalopathy in multiple myeloma.

Aim: Daratumumab, a CD38 monoclonal antibody, has been widely used in patients with multiple myeloma. Although a variety of adverse events have been reported, consciousness impairment has not been reported yet. We report a case of encephalopathy associated with daratumumab. Case presentation: A 57-year-old male, diagnosed with relapsed multiple myeloma, was treated with daratumumab. He developed a loss of consciousness after the first administration. Cerebral spinal fluid and magnetic resonance imaging of the brain suggested encephalopathy. Conclusion: It is recommended to be aware of rare but life threatening side effects of daratumumab. We present a case of rare encephalopathy characterized by consciousness disorder associated with daratumumab, which was successfully resolved on prompt institution of steroids, although the mechanism was unknown.

Daratumumab is a drug. It is used to treat multiple myeloma. Many patients use this drug. It has many side effects. But consciousness disorder is rare. A 57-year-old male was diagnosed with multiple myeloma. He was treated with daratumumab. He became unconscious after this treatment. Steroids helped his recovery.

A real-world pharmacovigilance study of FDA Adverse Event Reporting System (FAERS) events for Bruton's tyrosine kinase inhibitors (BTKis) single and its combination therapy.

BACKGROUND: Bruton's tyrosine kinase inhibitors (BTKis) are targeted treatments for B-cell tumors but have significant side effects. This study assesses and contrasts the side effects of BTKis alone and its four combination therapies. RESEARCH DESIGN AND METHODS: The reporting odds ratio (ROR) was used to analyze the data on three BTKis monotherapies and combinations of ibrutinib with rituximab, obinutuzumab, venetoclax, and lenalidomide in the FDA Adverse Event Reporting System (FAERS) database up to December 2022. RESULTS: We analyzed the top 20 PTs for each treatment regimen. In monotherapies, atrial fibrillation (ROR (95% CI): 9.88 (9.47-10.32)) in zanubrutinib and rash (6.97 (5.42-8.98)) in acalabrutinib had higher associations. In combinations, infection (6.86 (6.11-7.70)), atrial fibrillation (27.96 (22.61-34.58)) and myelosuppression (10.09 (8.89-11.46)) were vital signals when ibrutinib was combined with obinutuzumab, and pyrexia (4.22 (2.57-6.93)) had a high signal value when combined with lenalidomide. Hemorrhage had a lower signal value when combined with venetoclax compared to ibrutinib alone (2.50 (2.18-2.87) vs 3.60 (3.52-3.68)). CONCLUSIONS: The ibrutinib-obinutuzumab combo has the highest risk of infection, atrial fibrillation, and myelosuppression, and the ibrutinib-lenalidomide combo has the highest risk of pyrexia. However, the ibrutinib-venetoclax combo has a lower risk of hemorrhage than monotherapy.

Measuring integrity and fidelity of program implementation: Validating an instrument designed for school renewal.

In this study, we attempted to explore with instrumentation that could provide a good means to measure integrity and fidelity of program implementation. The instrument, High Integrity and Fidelity Implementation for School Renewal, was created using a comprehensive review of the literature to provide insights into the implementation integrity and fidelity when principals renew a school. Data from 1097 teachers were used to examine the instrument for construct validity by means of factorial validity and convergent validity. We used confirmatory factor analysis to compared five factorial structures of the instrument, resulting in the identification of a four-factor structure (coming from the comprehensive review of the literature) as the best fitting structure to the data. Strong convergent validity of the instrument was confirmed by correlating the instrument with a psychometrically established instrument measuring a similar construct. Finally, McDonald's Omega indicated strong internal consistency of the instrument in our reliability analysis.

Salvianolate injection for hypertensive nephropathy patients who were using valsartan: A systematic review and meta-analysis.

Background: The treatment of hypertensive nephropathy has remained unchanged for many years. Salvianolate is the main active component extracted from Salvia Miltiorrhiza. The current studies seem to suggest that salvianolate has a certain therapeutic effect on hypertensive nephropathy. Objective: The purpose of this meta-analysis is to evaluate the effect and safety of salvianolate on hypertensive nephropathy under the condition of standardized use of valsartan. Methods: We conducted a systematic search (unlimited initial date to 22 October 2022) in PubMed, Web of Science, the Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang Data knowledge service platform, China Science and Technology Journal Database, China Biomedical Literature Service System. Searching for the study of salvianolate on hypertensive nephropathy. Two reviewers independently included the study that met the inclusion criteria, and extracted data, evaluated the quality of the study. We use RevMan5.4 and stata15 software for this meta-analysis. We use GRADEprofiler 3.2.2 software for evidence quality assessment. Results: This meta-analysis included seven studies (525 patients). Compared with the use of valsartan combined with conventional treatment, salvianolate combined with valsartan and conventional treatment can further improve the efficacy (RR = 1.28, 95%CI:1.17 to 1.39), reduce blood pressure [systolic blood pressure (MD = 8.98, 95%CI:-12.38 to -5.59); diastolic blood pressure (MD = 5.74, 95%CI:-7.20 to -4.29)], serum creatinine (MD = -17.32, 95%CI:-20.55 to -14.10), blood urea nitrogen (MD = -1.89, 95%CI:-3.76 to -0.01), urine microalbumin (MD = -23.90, 95%CI:-26.54 to -21.26), and urinary protein to creatinine ratio (MD = -1.92, 95%CI:-2.15 to -1.69), cystatin C (MD = -1.04, 95%CI: -1.63 to -0.45) and increase calcitonin gene-related peptide (MD = 18.68, 95%CI:12.89 to 24.46) without increasing adverse reactions (RR = 2.20, 95%CI:0.52 to 9.40). But it has no additional effect on endothelin-1 and malondialdehyde. The quality of evidence ranged from moderate to very low. Conclusion: This meta-analysis shows that the salvianolate can further improve renal function of hypertensive nephropathy patients based on valsartan was used. Therefore, salvianolate can be used as a clinical supplement for hypertensive nephropathy. However, the quality of the evidence is not high due to the uneven quality of the included studies and the insufficient sample size, we still need a lot of large sample size studies with more perfect design to confirm these results. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022373256, identifier CRD42022373256.