The introduction to and inspiration from haematological management of major haemorrhage: a British Society for Haematology guideline / 中国输血杂志

Evidenced based and practical guidelines have important role in the decrease of mobility and mortality of the patients with major haemorrhage. Recently, British Society for Haematology updated a guideline on haematological management of major haemorrhage, which provides the recommendations in general and on alternatives to transfusion, obstetric haemorrhage, gastrointestinal haemorrhage, trauma and surgery, and the good practice statements for laboratory/organisational support. The comprehensive and instructive recommendations presented in the guideline will be good references for and assist in the education and development of the guidelines or protocols for the management of the patient with major haemorrhage in China.

Research advances in immunotherapy for hepatocellular carcinoma / 临床肝胆病杂志

Hepatocellular carcinoma (HCC) has an insidious onset, and most patients are in the advanced stage when attending the hospital and thus lose the opportunity for radical surgical resection, which results in the poor prognosis of patients. With the development of clinical treatment, the treatment of advanced HCC has gradually transitioned from the relatively single and limited treatment options in the past to the new model of comprehensive treatment. In recent years, immunotherapy, represented by immune checkpoint inhibitors (ICIs), has become widely used in clinical practice. At present, a number of clinical studies have been conducted for immunotherapy combined with local and targeted antitumor therapy, and in particular, ICIs combined with targeted therapy have become a research hotspot in the field of HCC treatment. This article reviews the research advances in immunotherapy for the treatment of HCC.

Transformation of primary myelofibrosis to B-cell acute lymphoblastic leukemia: report of 1 case and review of literature / 白血病·淋巴瘤

Objective:To investigate the pathogenesis and prognosis of transformation of primary myelofibrosis (PMF) to B-cell acute lymphoblastic leukemia (B-ALL).Methods:The diagnosis and treatment process of a patient transferred from PMF to B-ALL in Affiliated Tumor Hospital of Zhengzhou University in November 2018 were retrospectively analyzed, and the relevant literature was reviewed.Results:The patient was a 64-year-old female, she was initially diagnosed with PMF, and then she developed B-ALL 17 months later after receiving treatment of prednisone, danazole, levamisole, aspirin, thalidomide and jaktinib. After induction therapy, the patient received 8 months of continuous remission, and then the reexamination showed relapse. There was no remission after reinduction therapy. The patient gave up treatment and was discharged 2 months later. JAK2 V617F gene mutation was positive before and after leukemia transformation.Conclusions:The patients with transformation of PMF to B-ALL have poor clinical prognosis and short survival time. The possible mechanism of its transformation may be related to additional genetic events or certain high-risk genes. However, the specific mechanism is still unclear, and further investigation of the etiology is needed to seek targeted treatment.

Bioinformatics Analysis of Microarray Data in Myelodysplastic Syndrome Based on Gene Expression Omnibus Database / 中国实验血液学杂志

OBJECTIVE@#To identify the key genes and explore mechanisms in the development of myelodysplastic syndrome (MDS) by bioinformatics analysis.@*METHODS@#Two cohorts profile datasets of MDS were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed gene (DEG) was screened by GEO2R, functional annotation of DEG was gained from GO database, gene ontology (GO) enrichment analysis was performed via Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and key genes were screened by Matthews correlation coefficient (MCC) based on STRING database.@*RESULTS@#There were 112 DEGs identified, including 85 up-regulated genes and 27 down-regulated genes. GO enrichment analysis showed that biological processes were mainly enriched in immune response, etc, cellular component in cell membrane, etc, and molecular function in protein binding, etc. KEGG signaling pathway analysis showed that main gene enrichment pathways were primary immunodeficiency, hematopoietic cell lineage, B cell receptor signaling pathway, Hippo signaling pathway, and asthma. Three significant modules were screened by Cytoscape software MCODE plug-in, while 10 key node genes (CD19, CD79A, CD79B, EBF1, VPREB1, IRF4, BLNK, RAG1, POU2AF1, IRF8) in protein-protein interaction (PPI) network were screened based on STRING database.@*CONCLUSION@#These screened key genes and signaling pathways are helpful to better understand molecular mechanism of MDS, and provide theoretical basis for clinical targeted therapy.

Hepatocellular carcinoma-derived exosomal miRNA-761 regulates the tumor microenvironment by targeting the SOCS2/JAK2/STAT3 pathway / 世界急诊医学杂志（英文）

@#BACKGROUND: Exosomes and exosomal microRNAs have been implicated in tumor occurrence and metastasis. Our previous study showed that microRNA-761 (miR-761) is overexpressed in hepatocellular carcinoma (HCC) tissues and that its inhibition affects mitochondrial function and inhibits HCC metastasis. The mechanism by which exosomal miR-761 modulates the tumor microenvironment has not been elucidated. METHODS: Exosomal miR-761 was detected in six cell lines. Cell counting kit-8 (CCK-8) and transwell migration assays were performed to determine the function of exosomal miR-761 in HCC cells. The luciferase reporter assay was used to analyze miR-761 target genes in normal fibroblasts (NFs). The inhibitors AZD1480 and C188-9 were employed to determine the role of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in the transformation of cancer-associated fibroblasts (CAFs). RESULTS: In this study, we characterized the mechanism by which miR-761 reprogrammed the tumor microenvironment. We found that HCC-derived exosomal miR-761 was taken up by NFs. Moreover, HCC exosomes affected the tumor microenvironment by activating NFs via suppressor of cytokine signaling 2 (SOCS2) and the JAK2/STAT3 signaling pathway. CONCLUSIONS: These results demonstrated that exosomal miR-761 modulated the tumor microenvironment via SOCS2/JAK2/STAT3 pathway-dependent activation of CAFs. Our findings may inspire new strategies for HCC prevention and therapy.

Time-dependent injury of mouse cerebral cortex and hippocampus by acute hypoxia / 生理学报

The aim of this study was to investigate the harmful effects of acute hypoxia on mouse cerebral cortex and hippocampus and the underlying mechanism. Mouse model of acute hypoxia was constructed by using a sealed glass jar. Laser speckle contrast imaging was used to detect the changes of cerebral blood flow after different time duration of hypoxia. Total superoxide dismutase (T-SOD) and malondialdehyde (MDA) assay kits were used to detect oxidative stress in cerebral cortex and hippocampus. Immunofluorescent staining was used to detect neuroinflammatory response of microglia in the cerebral cortex and hippocampus. One-step TUNEL method was used to detect neuronal apoptosis. The results showed that, compared with non-hypoxia (0 min hypoxia) group, 30 min hypoxia group exhibited decreased cerebral blood flow, higher percentage of CD68+/Iba1+ microglia, and increased neural apoptosis in the cerebral cortex and hippocampus. Compared with 30 min group, 60 min hypoxia group showed significantly decreased cerebral blood flow, increased MDA content in the cortex, as well as greater percentage of CD68+/Iba1+ microglia and neuronal apoptosis in the cerebral cortex and hippocampus. These results suggest that acute hypoxia damages brain tissue in a time-dependent manner and the oxidative stress and neuroinflammation are important mechanisms.

Cryptobiosis-inspired assembly of "AND" logic gate platform for potential tumor-specific drug delivery

Developing tumor-specific drug delivery systems with minimized off-target cargo leakage remains an enduring challenge. In this study, inspired from the natural cryptobiosis explored by certain organisms and stimuli-responsive polyphenol‒metal coordination chemistry, doxorubicin (DOX)-conjugated gelatin nanoparticles with protective shells formed by complex of tannic acid and Fe

Norlichexanthone purified from plant endophyte prevents postmenopausal osteoporosis by targeting ER

Although different types of drugs are available for postmenopausal osteoporosis, the limitations of the current therapies including drug resistances and adverse effects require identification of novel anti-osteoporosis agents. Here, we defined that norlichexanthone (NOR), a natural product, is a ligand of estrogen receptor-alpha (ER

Clinical analysis of COVID-19 blood recipients: 81 patients / 中国输血杂志

【Objective】 To retrospectively analyze the transfusion records of COVID-19 patients from Feb to Mar 2020 in the Optical Valley Branch of Tongji Hospital in Wuhan, and summarize the clinical features and blood use of those patients. 【Methods】 1) The utilization of blood components in 81 blood recipients were collected and retrospectively analyzed; 2) Propensity score matching (PSM, by the clinical classification of COVID-19) was used to match the transfused and non-transfused patients according to the ratio of 1∶2, and the clinical features of the two groups were compared. 【Results】 The total transfusion rate in our hospital was 5.5%(81/1 463), among which 88.9%(72/81)transfused red blood cell (RBC). Ten patients received RBC transfusion > 20 U, consumed 48.3%(330/680)RBC, 57.5%(53 500/93 100)plasma, 36.2%(42/116)platelets, and 62.3%(114.25/183.25)cryoprecipitates due to ECMO or gastrointestinal bleeding. Compared to non-transfused patients, transfused patients showed worse lab-indexes related to inflammation, infection, and coagulation at admission, higher incidences of acute liver, kidney and cardiac injury, admission to the ICU and mortality(P<0.01). 【Conclusion】 The related functional indexes and prognosis of transfused COVID-19 patients were significantly worse than non-transfused ones. RBC transfusions were dominant, and massive blood transfusions were seldom.

Discovery of a subtype-selective, covalent inhibitor against palmitoylation pocket of TEAD3

The TEA domain (TEAD) family proteins (TEAD1‒4) are essential transcription factors that control cell differentiation and organ size in the Hippo pathway. Although the sequences and structures of TEAD family proteins are highly conserved, each TEAD isoform has unique physiological and pathological functions. Therefore, the development and discovery of subtype selective inhibitors for TEAD protein will provide important chemical probes for the TEAD-related function studies in development and diseases. Here, we identified a novel TEAD1/3 covalent inhibitor (DC-TEADin1072) with biochemical IC

Repurposing antimycotic ciclopirox olamine as a promising anti-ischemic stroke agent

Ischemic stroke is a severe disorder resulting from acute cerebral thrombosis. Here we demonstrated that post-ischemic treatment with ciclopirox olamine (CPX), a potent antifungal clinical drug, alleviated brain infarction, neurological deficits and brain edema in a classic rat model of ischemic stroke. Single dose post-ischemic administration of CPX provided a long-lasting neuroprotective effect, which can be further enhanced by multiple doses administration of CPX. CPX also effectively reversed ischemia-induced neuronal loss, glial activation as well as blood-brain barrier (BBB) damage. Employing quantitative phosphoproteomic analysis, 130 phosphosites in 122 proteins were identified to be significantly regulated by CPX treatment in oxygen glucose deprivation (OGD)-exposed SH-SY5Y cells, which revealed that phosphokinases and cell cycle-related phosphoproteins were largely influenced. Subsequently, we demonstrated that CPX markedly enhanced the AKT (protein kinase B, PKB/AKT) and GSK3 (glycogen synthase kinase 3) phosphorylation in OGD-exposed SH-SY5Y cells, and regulated the cell cycle progression and nitric oxide (NO) release in lipopolysaccharide (LPS)-induced BV-2 cells, which may contribute to its ameliorative effects against ischemia-associated neuronal death and microglial inflammation. Our study suggests that CPX could be a promising compound to reduce multiple ischemic injuries; however, further studies will be needed to clarify the molecular mechanisms involved.

Safety and efficacy of regional transport combined with PCI model in patients with STEMI after thrombolysis in northwest China / 中华心血管病杂志

Objective: To investigate the safety and efficacy of regional transport to percutaneous coronary intervention(PCI) hospitals from non-PCI hospitals after thrombolysis in patients with acute ST-segment elevation myocardial infarction(STEMI) in northwest China. Methods: In this retrospective study, 1 062 STEMI patients who were transferred from non-PCI hospitals within 24 hours from symptom onset, during January 2015 and January 2019 in the First Hospital of Lanzhou University, were included. According to the treatment strategy, they were divided into two groups, namely intravenous thrombolysis combined with PCI group(n=240), and primary PCI group(n=822). Observation endpoint were in-hospital adverse cardiovascular and cerebrovascular events and bleeding events, Including all-cause death, ischemic stroke, malignant arrhythmia, intracranial hemorrhage and hemorrhage with hemoglobin decrease≥50 g/L. Results: A total of 1 062 STEMI patients were included(age was (61±12) years old), with 905 males (85.2%). The proportion of grade 0 TIMI blood flow in the primary PCI group before operation was significantly higher than that in the thrombolysis combined with PCI group(63.0%(518/822) vs. 36.3%(87/240)， P<0.001). Compared with primary PCI group, the time from symptom onset to first medical contact(2.11(1.00, 4.00)hours vs.3.00(1.13, 7.07)hours, P<0.001) and reperfusion in thrombolysis combined with PCI group(3.07(1.83, 4.87)hours vs. 6.92(4.07, 11.15) hours, P<0.001) were significantly shorter. The proportion of all-cause death was significantly higher in the primary PCI group than that in the thrombolysis combined with PCI group (1.8%(15/822) vs. 0, P=0.03). There was no significant difference in hemorrhage, ischemic stroke and malignant arrhythmia between the two groups(all P>0.05). Conclusions: For STEMI patients initially hospitalized in non-PCI hospitals, regional transport combined with PCI is feasible and effective. It does not significantly increase the risk of bleeding and cardiovascular and cerebrovascular events, with shorter time from symptom onset to myocardial reperfusion.

Perioperative nutrition management for critically ill patients based on the concept of enhanced recovery after surgery / 医学研究生学报

Nutrition management based on enhanced recovery after surgery(ERAS) programs is a continuously evolving field in perioperative critical illness. Preoperative and post-operative nutritional measurement of ERAS are the core of perioperative nutrition. For critically ill patients, enteral nutrition assessment checklist may be able to improve the quality of enteral nutrition implementation. The management of gastric tube jejunal nutrition tube needs to be personalized according to the patient's condition. Auscultation-assisted bare-handed jejunal tube placement may make it easier for ICU patients to establish jejunal nutrition pathways.This paper will discuss nutrition management based on ERAS.

Prognosis of clonal chromosomal abnormalities in Philadelphia negative metaphases cells in chronic myeloid leukemia with tyrosine kinase inhibitor therapy / 中华血液学杂志

Objective@#To investigate the characteristics and prognosis of clonal chromosomal abnormalities appearing in Philadelphia negative metaphases (CCA/Ph-) cells in chronic myeloid leukemia (CML) with tyrosine kinase inhibitor (TKI) therapy.@*Methods@#The clinical data of 30 cases with CCA/Ph- during TKI treatment in Henan Cancer Hospital from August 2007 to July 2017 were retrospectively analyzed. The univariate factor was analyzed by Kaplan-Meier method. Multiple-factor was analyzed by Cox proportional risk model.@*Results@#Of the 30 cases, 19 (63.3%) were males. At the first detection of CCA/Ph- the median age was 44 (rang 14-68) years old and the median treatment of TKI was 13 (rang 2-94) months. The clones proportion of first detected CCA/Ph-≥ 50% was found in 18 (60.0%) cases. TKI treatment for 3 months with BCR-ABLIS less than 10% was seen in 14 (46.7%) patients. 63.3% (19/30) of CCA/Ph- was transient (only one time) and 36.7% (11/30) was repeated (≥2 times) . Trisomy 8 dominant accounted for 60.0% (18/30) , -7/7q- for 13.3% (4/30) , loss of chromosome Y 6.7%. With a median of follow-up 50 months, 76.7% (23/30) cases were in complete cytogenetic response (CCyR) ; 63.3% (19/30) in major molecular response (MMR) , 43.3% (13/30) in undetectable minimal residual disease (UMRD) . The median event-free survival rate of (EFS) were 44 months, and 2-year and 5-year EFS were (82.1±7.3) % and (52.4±12.8) %, respectively. The median overall survival (OS) were 50 months, and 2-year and 5-year OS rates were (92.6±5.0) % and (77.2±14.7) %, respectively. Univariate analysis shows that the 2-year EFS of who in males, more than 2 times CCA/Ph-, BCR-ABLIS>10% at 3 months after TKI were significantly lower than women, transient CCA/Ph-, and BCR-ABLIS≤10% (P<0.05) . The 2-year OS rate in whom the occurrence frequency of CCA/Ph- more than twice was significantly lower than those with transient CCA/Ph- (P<0.05) . Multivariate analysis showed that CCA/Ph- was an independent risk factor (RR=4.741, 95%CI 1.21-18.571, P=0.018) for EFS in CML patients.@*Conclusion@#Trisomy 8, -7/7q-, and -Y were the most common CCA/Ph- during TKI treatment, with high clones proportion of ≥50%. CCA/Ph- mainly occurred transiently or was permanent occasionally. CCA/Ph- recurrence (≥2 times) was an independent risk factor for EFS and OS in CML with TKI.

Application of early goal-directed sedation with bispectral index in sedation management of severe patients in ICU / 中国医师杂志

Objective The bispectral index (BIS) was introduced into the sedation strategy of critical patients in intensive care unit (ICU) and replaced the Richmond agitation sedation scale (RASS).The ventilation time,ICU length of stay,and 90-day mortality were compared between the two groups of patients who performed early goal-directed sedation (EGDS) or standard traditional directed sedation (STDS) strategies.Methods A prospective controlled study of severe patients with mechanical ventilation ≥48 h in ICU (20 cases from April 2016 to May 2017,46 cases from June 2017 to April 2018) were randomly divided into EGDS or STDS group.There were no significant differences in age,gender,and acute physiology and chronic health evaluation score Ⅱ (APACHE Ⅱ) score between the two groups in the two periods.The correlation between RASS and BIS was analyzed in the first period.The BIS of the patients in a RASS range of (-2-1) was 73.65 ± 7.87 in the EGDS group,and that of RASS range of (-3--1) was 64.14 ± 7.25 in the STDS group.The above BIS was applied to the two sedation strategies in the second period respectively.The ventilation time,ICU length of stay,and 90-day mortality were recorded.Results There was no significant difference in the ventilation time between the two groups [(164.12 ± 137.96) h and (155.33 ±64.86)h,P =0.08].ICU length of stay of the EGDS group was longer than that of the STDS group.The 90-day mortality of the EGDS group was higher than that of the STDS group.Conclusions Correlations between RASS and BIS were found in this study,and BIS can be used for sedation assessment in ICU patients.Large sample study is still needed to compare EGDS and STDS with BIS.

Traditional Chinese Medicine as a Remedy for Male Infertility: A Review

Male infertility (MI) is a complex multifactorial disease, and idiopathic infertility accounts for 30% of cases of MI. At present, the evidence for the effectiveness of empirical drugs is limited, and in vitro fertilization is costly and may increase the risk of birth defects and childhood cancers. Therefore, affected individuals may feel obliged to pursue natural remedies. Traditional Chinese medicine (TCM) may represent a useful option for infertile men. It has been demonstrated that TCM can regulate the hypothalamic-pituitary-testicular axis and boost the function of Sertoli cells and Leydig cells. TCM can also alleviate inflammation, prevent oxidative stress, reduce the DNA fragmentation index, and modulate the proliferation and apoptosis of germ cells. Furthermore, TCM can supply trace elements and vitamins, ameliorate the microcirculation of the testis, decrease the levels of serum anti-sperm antibody, and modify epigenetic markers. However, the evidence in favor of TCM is not compelling, which has hindered the development of TCM. This review attempts to elucidate the underlying therapeutic mechanisms of TCM. We also explore the advantages of TCM, differences between TCM and Western medicine, and problems in existing studies. Subsequently, we propose solutions to these problems and present perspectives for the future development of TCM.

Application of Tri-Lock bone preservation stem in acetabular protrusion combined with shorten defect of femoral head and neck / 中国骨伤

<p><b>OBJECTIVE</b>To evaluate the manipulation technique and clinical outcome of Tri-Lock bone preservation stem for acetabular protrusion combined with shorten defect of femoral head and neck.</p><p><b>METHODS</b>From January 2013 to December 2015, 10 patients(12 hips) with acetabular protrusion combined with shorten defect of femoral head and neck were treated with total hip arthroplasty(THA) including 5 males and 5 female with an average age of(51.6±3.0) years old ranging from 42.5 to 67.5 years old. The acetabular prostheses were all biological prosthesis with the ceramic lining, the whole ceramic femoral head was used in all the cases. The posterior-lateral hip incision was adopted in the surgery. The follow-up was carried out in 12 months after the surgery, and later once a year. The Harris score system in growth of femoral side described was used to assess the joint function of the patients before and after the surgery.</p><p><b>RESULTS</b>Ten patients were followed up for 8 to 48 months with an average of 33.0±3.5. All the incisions healed well and there were no complications such as femoral fracture, infection, dislocation and neurovascular injuries. The biological compression of the acetabulum and the stem of the femur was realized immediately after operation in 10 patients(12 hips). X-ray at 3 months after the operation showed bone growth were extended in a wide range, which could achieve bone fixation, no loosening and re-invagination. The range of hip movement increased from (45.8±7.5)° to (90.0±6.5)° at the final follow-up, with flexion increased to (89.0±6.0)°, abduction increased to (35.5±7.3)° and internal rotation increased to(31.8±6.6)°, the outer rotation increased to(32.6±5.2)°. The mean Harris scores had improved from 45.7±7.5 pre-operatively to 93.5±8.0 post-operatively, there was statistically significant difference between before and after surgery (=144.832,<0.05).</p><p><b>CONCLUSIONS</b>Combined with acetabular treatment, Tri-Lock bone retention of the femoral stem in the treatment of femoral head and neck with shortening of the acetabular retraction and severe hip joint soft tissue contracture in patients, could be well pressed and retained more bone. The reconstruction of the acetabulum and the delamination of soft tissue are required during the operation. The results were safe and satisfactory in the middle and short term follow-up.</p>

Normal saline for intravenous fluid therapy in critically ill patients / 中华创伤杂志(英文版)

The efficacy and safety of normal saline (NS) for fluid therapy in critically ill patients remain controversy. In this review, we summarized the evidence of randomized controlled trials (RCTs) which compared NS with other solutions in critically ill patients. The results showed that when compared with 6% hydroxyethyl starch (HES), NS may reduce the onset of acute kidney injury (AKI). However, there is no significant different in mortality and incidence of AKI when compared with 10% HES, albumin and buffered crystalloid solution. Therefore, it is important to prescribe intravenous fluid for patients according to their individual condition.

Treatment of a patient with considerably thin alveolar bone and severe open bite / 华西口腔医学杂志

This case report describes the treatment of a 25-year-old woman with a severe open bite. This patient presented a grade Ⅲ open bite, considerably thin alveolar bone, and evident labial buccal and lingual root form. The open bite was corrected by fixed orthodontic treatment and masticatory exercises. However, the increased pressure in the labial muscle caused by lip muscle exercise suppressed the canines, which resulted in the protrusion of the apices of canine roots out of the alveolar bone. Afterward, HX brackets, instead of self-locking, were used and bonded reversely in the occlusal-gingival direction on the upper canines. The lip muscle exercises were decreased. After adjustment, the roots penetrated back into the cancellous bone, the severe open bite was corrected, and a normal overbite and overjet were achieved. ClassⅠcanine and molar relationships were established. The masticatory function and profile were both considerably improved. This case report showed that a severe nonskeletal open bite can be corrected using orthodontic treatments combined with masticatory exercises.

Efficacy of endoscopic submucosal dissection for colorectal submucosal tumors / 中国内镜杂志

Objective To evaluate the outcomes and safety of ESD in colorectal SMTs. Methods Between January 2011 and January 2017, we performed ESD on 68 consecutive colorectal SMTs in 67 patients. We evaluated the clinical outcomes of all said cases. Results The most common type of the 68 colorectal SMTs was neuroendocrine tumor (42/68, 61.8%), followed by lipoma (20/68, 29.4%). Most of neuroendocrine tumors (41/42) were located in rectum, and most of lipomas (18/20) were located in colon. Among the 46 tumors which were evaluated by endoscopic ultrasonography (EUS) before ESD,38 tumors (82.6%) were located in the submucosal layer, and 31 tumors (67.4%) were hypoecho. Our overall endoscopic en bloc resection rate was 100.0%, and our R0 resection rate was 94.1% respectively. Our perforation rate of ESD was 6.0%, delayed bleeding rate 1.5%. None of the patients need surgical intervention because of complication. Follow-up rate was 95.5%, no recurrence or metastasis was observed during the median follow-up period 33 months (range 3~75 months). Conclusion EUS is conductive to the diagnosis of colorectal SMTs before ESD. ESD is a safe and effective treatment for colorectal SMTs.