Objective: To evaluate the efficacy and safety of bendamustine combined with pomalidomide and dexamethasone (BPD regimen) in the treatment of relapsed multiple myeloma (MM) with extramedullary disease. Methods: This open, single-arm, multicenter prospective cohort study included 30 relapsed MM patients with extramedullary disease diagnosed in seven hospitals including Qingdao Municipal Hospital. The patients were treated with BPD regimen from February 2021 to November 2022. This study analyzed the efficacy and adverse reactions of the BPD regimen. Results: The median age of the 30 patients was 62 (47-72) years, of which 18 (60% ) had first-time recurrence. The overall response rate (ORR) of the 18 patients with first-time recurrence was 100%, of which three (16.7% ) achieved complete remission, 10 (55.5% ) achieved very good partial remission (VGPR), and five (27.8% ) achieved partial remission (PR). The ORR of 12 patients with recurrence after second-line or above treatment was 50%, including zero patients with ≥VGPR and six patients (50% ) with PR. Three cases (25% ) had stable disease, and three cases (25% ) had disease progression. The one-year progression free survival rate of all patients was 65.2% (95% CI 37.2% -83.1% ), and the 1-year overall survival rate was 90.0% (95% CI 76.2% -95.4% ). The common grade 3-4 hematology adverse reactions included two cases (6.7% ) of neutropenia and one case (3.3% ) of thrombocytopenia. The overall adverse reactions are controllable. Conclusions: The BPD regimen has good efficacy and tolerance in relapsed MM patients with extramedullary disease.
Humans ; Middle Aged ; Aged ; Multiple Myeloma/drug therapy* ; Bendamustine Hydrochloride/therapeutic use* ; Prospective Studies ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

China ; Cognition ; Digestive System Surgical Procedures ; Enhanced Recovery After Surgery ; Humans ; Length of Stay

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To investigate the effect of suppressing high-mobility group box 1 (HMGB1) on neuronal autophagy and apoptosis in rats after intracerebral hemorrhage (ICH) in rats. METHODS: Rat models of ICH induced by intracerebral striatum injection of 0.2 U/mL collagenase Ⅳ were treated with 1 mg/kg anti-HMGB1 mAb or a control anti-IgG mAb injected via the tail immediately and at 6 h after the operation (n=5). The rats in the sham-operated group (with intracranial injection of 2 μL normal saline) and ICH model group (n=5) were treated with PBS in the same manner after the operation. The neurological deficits of the rats were evaluated using modified neurological severity score (mNSS). TUNEL staining was used to detect apoptosis of the striatal neurons, and the expressions of HMGB1, autophagy-related proteins (Beclin-1, LC3-Ⅱ and LC3-Ⅰ) and apoptosis-related proteins (Bcl-2, Bax and cleaved caspase-3) in the brain tissues surrounding the hematoma were detected using Western blotting. The expression of HMGB1 in the striatum was detected by immunohistochemistry, and serum level of HMGB1 was detected with ELISA. RESULTS: The rat models of ICH showed significantly increased mNSS (P < 0.05), which was markedly lowered after treatment with anti- HMGB1 mAb (P < 0.05). ICH caused a significant increase of apoptosis of the striatal neurons (P < 0.05), enhanced the expressions of beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), lowered the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and increased the content of HMGB1 (P < 0.05). Treatment with anti-HMGB1 mAb obviously lowered the apoptosis rate of the striatal neurons (P < 0.05), decreased the expressions of Beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), increased the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and reduced the content of HMGB1 in ICH rats (P < 0.05). CONCLUSION Down- regulation of HMGB1 by anti-HMGB1 improves neurological functions of rats after ICH possibly by inhibiting autophagy and apoptosis of the neurons.
Animals ; Apoptosis ; Apoptosis Regulatory Proteins/metabolism* ; Autophagy ; Beclin-1 ; Caspase 3/metabolism* ; Cerebral Hemorrhage/therapy* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein/metabolism*

Objective:To evaluate the safety and feasibility of the in-situ needle fenestration combined with the in vitro physician modified fenestration technique to reconstruct supra-aortic branches during thoracic endovascular aortic repair (TEVAR) for aortic arch lesions requiring landing at Z0 and Z1.Methods:From Nov 2017 to Dec 2019, eighteen patients who underwent both the in-situ needle fenestration and the in vitro physician modified fenestration techniques to extend the proximal landing zone to Z0 and Z1 during TEVAR were included in our study.Results:Sixteen patients underwent in vitro physician modified fenestration ,two patients underwent in vitro physician modified fenestration to reconstruct both the left common carotid artery and the innominate artery. All eighteen patients received in-situ needle fenestration to preserve the left subclavian artery. Supra aortic branches were preserved in all patients (38/38, 100%). There was no Type Ⅰ endoleak. Type Ⅱ endoleak was found in four paitnets (4/18). Type Ⅲ endoleak occurred in one patient (1/18). Type Ⅳ endoleak in four patients (4/18). Type Ⅲ endoleak needed open aortic arch repair 6 months later. The median follow-up time was 12 months. One (1/18) died in 12 months and the other patients were doing well.Conclusions:The joint application of the in-situ needle fenestration and the in vitro physician modified fenestration to reconstruct supra-aortic branches during TEVAR for aortic arch pathologies requiring landing at Z0 and Z1 was satisfactory.

An auxiliary isolation device of cupping therapy for cross-infection prevention is designed to reduce the disinfection steps and be against cross transmission. This device is composed of a disposable isolation unit made of fire proof plastic material and a disposable cup-mouth fixator made of elastic material. The disposable isolation unit includes two parts, the cup neck isolation unit and the inner isolation unit of fire cup. These two parts connect with the disposable cup-mouth fixator. All of those three sections of the device are center-connected ring-like structure. This device can well prevent the direct contact of fire cup with the patient's skin surface, characterized as safety protection, simple operation and saving time and manpower.
Cupping Therapy ; Humans

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
Adult ; Aged ; Betacoronavirus ; genetics ; isolation & purification ; Coronavirus Infections ; diagnostic imaging ; therapy ; virology ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnostic imaging ; therapy ; virology ; Tomography, X-Ray ; Treatment Outcome

Background: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. Methods: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital, Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. Results: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8–99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6–87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. Conclusion: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.