BACKGROUND:Haploidentical hematopoietic stem cell transplantation is associated with a higher rate of graft rejection and therefore often requires a higher CD34+ cell dose,but the findings reported in existing studies regarding the relationship between CD34+ cell dose and study endpoints after allogeneic hematopoietic stem cell transplantation are controversial. OBJECTIVE:To investigate the effect of CD34+ cell dose on clinical outcomes of haploidentical hematopoietic stem cell transplantation for malignant hematological diseases. METHODS:135 patients who underwent haploidentical hematopoietic stem cell transplantation at Hematopoietic Stem Cell Transplantation Center,Department of Hematology,First Affiliated Hospital of Zhengzhou University between January 2019 and December 2021 were included.Combining the results of previous studies and our center's experience,the cohort was divided into two groups using a CD34+ cell count of 5.0×106/kg as the cut-off point.Clinical outcomes related to graft implantation,relapse incidence,non-relapse mortality,overall survival and progression-free survival were evaluated in both groups. RESULTS AND CONCLUSION:(1)CD34+ cell dose correlated with platelet engraftment,with platelets implanted earlier in the high-dose group than in the low-dose group(14 days vs.16 days,P=0.013).(2)There was no significant difference in 3-year overall survival between the two groups(67.5%vs.53.8%,P=0.257);nor was there a significant difference in progression-free survival between the two groups(65.6%vs.44.2%,P=0.106),but stratified analysis based on disease risk index revealed an association with elevated 3-year progression-free survival in the high-dose group among low-risk patients(72.0%vs.49.3%,P=0.036).(3)The cumulative 3-year relapse incidence was smaller in the high-dose group than in the low-dose group(16.0%vs.33.5%,P=0.05).(4)The rate of non-relapse mortality within 100 days was greater in the high-dose group than in the low-dose group,but there was no significant difference(17.3%vs.6.7%,P=0.070);stratified analysis revealed that non-relapse mortality within 100 days was significantly higher in the high-dose group than in the low-dose group(20.0%vs.3.3%,P=0.046).(5)In conclusion,CD34+ cell doses>5.0×106/kg promote early platelet implantation,improve 3-year progression-free survival in low-risk patients at transplantation and reduce the cumulative relapse incidence.However,in high-risk patients,high-dose CD34+ cells result in increased non-relapse mortality within 100 days after transplantation,which is considered to be possibly associated with an increased occurrence of severe acute graft versus host disease in the early post-transplantation period.Therefore,it is considered that graft versus host disease monitoring should be enhanced in patients who transfused high-dose CD34+ cells.

ObjectiveThe mechanisms underlying therapeutic efficacies of Detumescence Analgesic Plaster was analyzed based on "effect-target" associations. MethodBased on CNKI and PubMed databases， the chemical components of Artemisia seed， bastard speedwell， and menthol in Detumescence Analgesic Plaster were collected. The capacity of transdermal absorption was predicted based on the Encyclopedia of Traditional Chinese Medicine （ETCM 2.0）. Golden Triangle of compounds with Accepted used for candidate target prediction based on the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP v2.0）according to the similarity of chemical structures. At the same time， the SoFDA data platform was employed to collect the symptoms related to the efficacy of Detumescence Analgesic Plaster and its related genes information. In addition， based on the interaction between the above-mentioned candidate targets and their efficacy-related genes， the "effect-target" interaction network of Detumescence Analgesic Plaster was constructed. The key targets by topological features calculation， and functional mining was carried out to explain the efficacy mechanism of Detumescence Analgesic Plaster. ResultA total of 165 candidate targets were obtained based on ETCM 2.0 and TCMIP v2.0 databases， and symptoms related to the efficacy of clearing heat， detumescence， and relieving pain， as well as 1 744 related genes were collected based on the SoFDA database. Network construction and analysis showed that the core effect targets of Detumescence Analgesic Plaster were mainly involved in regulating the "immune-inflammation" balance of the body and maintaining the homeostasis of material and energy metabolism， blood circulation， and nervous system functions， and they were closely related to the efficacy of this prescription in clearing heat， reducing detumescence， and relieving pain. Among them， the heat clearing group of Detumescence Analgesic Plaster had the functions of heat clearing， detoxifying， antibacteria， and anti-inflammation. The biological function of its key effect target group was related to correcting the imbalance of "immune-inflammation" induced by pathogens. The detumescence group of Detumescence Analgesic Plaster had the functions of reducing water and swelling and resolving hard lumps， and the biological function of its core effect target group was related to improving microcirculation disturbance. The pain relieving group of Detumescence Analgesic Plaster had the functions of removing stasis， promoting blood circulation， and relieving pain， and its core effect target group was related to correcting the nervous system and the disorder of material and energy metabolism. ConclusionThe heat clearing， swelling reducing， and pain relieving effects of Detumescence Analgesic Plaster may be closely related to its act on related candidate targets， so as to correct the imbalance of "nerve-immunity-vascular-axis"， regulate neuronal excitability and inflammatory response， and intervene in material and energy metabolism. The relevant research results lay a theoretical foundation for clarifying the advantages of Detumescence Analgesic Plaster and assisting its clinical precise positioning.

Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality.Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenesis can result in different types of ribosomopathies in clinic,collectively known as ribosomopathy genes.Emerging data suggest that ribosomopathy patients exhibit a significantly heightened susceptibility to cancer.Abnormal ribosome biogenesis and dysregulation of some ribo-somopathy genes have also been found to be intimately associated with cancer development.The cor-relation between ribosome biogenesis or ribosomopathy and the development of malignancies has been well established.This work aims to review the recent advances in the research of ribosomopathy genes among human cancers and meanwhile,to excavate the potential role of these genes,which have not or rarely been reported in cancer,in the disease development across cancers.We plan to establish a theoretical framework between the ribosomopathy gene and cancer development,to further facilitate the potential of these genes as diagnostic biomarker as well as pharmaceutical targets for cancer treatment.

Objective:To observe the effects of ointment and massage on inflammation, oxidative stress and angiogenesis after skeletal muscle trauma, and to explore their mechanisms.Methods:Forty-two adult male Sprague-Dawley rats were randomly divided into a blank group ( n=6), an ointment and massage (O&M) group ( n=18) and a model group ( n=18). The blunt contusion model of gastrocnemius malformation was established in both the O&M and model groups using self-made percussion instruments. Two hours after successful modeling, the anti-inflammatory pain-relieving cream was applied to the injured area, and massaged evenly and gently for 5 minutes. That was repeated with an interval of 12 hours. No treatment was given to the model and blank groups. On the 1st, 3rd and 7th days after modeling, injured gastrocnemius muscles were resected after collecting abdominal blood. Hematoxylin-eosin (HE) staining and immunofluorescent (CD34) staining were applied, and serum superoxide dismutase (SOD) and malondialdehyde (MDA) contents were detected. Results:HE staining showed that at each time point the gastrocnemius muscle fibers of the model group were significantly more swollen and deformed, collapsed and dissolved than those of the blank group, with a large number of inflamed cells. The O&M group had better recovery, with more newly-generated muscle cells, less inflammatory infiltration and more normal cell shapes than the model group. Fluorescence was stronger in the O&M and model groups than in the blank group at each time point, with that of the O&M group significantly stronger than in the model group. The average SOD and MDA levels in the model and O&M groups were significantly higher than in the blank group, and on the 1st and 3rd days the O&M group′s average SOD level was significantly higher than the model group′s average, though by the 7th day there was no significant difference. The average MDA content of the O&M group was significantly lower than the model group′s average at each time point.Conclusion:Ointment and massage can effectively reduce the local inflammatory response and oxidative stress after a skeletal muscle injury. They can accelerate local angiogenesis, promoting the repair of damaged tissues.

BACKGROUND: Islet transplantation is currently considered the most promising method for treating insulin-dependent diabetes. The two most-studied artificial islets are alginate-encapsulated b cells or b cell spheroids. As three-dimensional (3D) models, both artificial islets have better insulin secretory functions and transplantation efficiencies than cells in twodimensional (2D) monolayer culture. However, the effects of these two methods have not been compared yet. Therefore, in this study, cells from the mouse islet b cell line Min6 were constructed as scaffold-free spheroids or alginate-encapsulated dispersed cells. METHODS: MIN6 cell spheroids were prepared by using Agarose-base microwell arrays. The insulin secretion level was determined by mouse insulin ELISA kit, and the gene and protein expression status of the MIN6 were performed by Quantitative polymerase chain reaction and immunoblot, respectively. RESULTS: Both 3D cultures effectively promoted the proliferation and glucose-stimulated insulin release (GSIS) of MIN6 cells compared to 2D adherent cells. Furthermore, 1% alginate-encapsulated MIN6 cells demonstrated more significant effects than the spheroids. In general, three pancreatic genes were expressed at higher levels in response to the 3D culture than to the 2D culture, and pancreatic/duodenal homeobox-1 (PDX1) expression was higher in the cells encapsulated in 1% alginate than that in the spheroids. A western blot analysis showed that 1% alginate-encapsulated MIN6 cells activated the phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase (AKT)/forkhead transcription factor FKHR (FoxO1) pathway more than the spheroids, 0.5% alginate-, or 2% alginate-encapsulated cells did. The 3D MIN6 culture, therefore, showed improved effects compared to the 2D culture, and the 1% alginate-encapsulated MIN6 cells exhibited better effects than the spheroids. The upregulation of PDX1 expression through the activation of the PI3K/AKT/FoxO1 pathway may mediate the improved cell proliferation and GSIS in 1% alginate-encapsulated MIN6 cells. CONCLUSION This study may contribute to the construction of in vitro culture systems for pancreatic islets to meet clinical requirements.

Objective:To investigate the distribution, drug resistance and clinical significance of bacteria and fungi in pancreatic juice of patients with severe acute pancreatitis (SAP).Methods:Data of patients with severe acute pancreatitis receiving ERCP treatment and pancreatic juice bacterial culture at Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University from Jan 2019 to Jun 2020 were retrospectively analyzed.Results:A total of 97 patients were included. Pathogens were isolated from 46 (47.42%) pancreatic juice samples, with 71 strains including 43 (60.56%) gram negative bacteria, 26 (36.62%) gram positive bacteria, and 2 (2.82%) fungi. The C-reactive protein (CRP), D-dimer and Balthazar CT Score in the culture positive group were higher than those in the culture negative group ( P < 0.05). The incidence of complications and pancreatic infection in the culture positive group was also significantly higher ( P < 0.05). Conclusions:The positive rate of pancreatic juice bacterial culture in the early stage of severe acute pancreatitis is high, in which Gram-negative bacteria are most common, followed by Gram-positive bacteria and fungi. The presence of pathogens in pancreatic juice predicts ensuing infections.

Proximity labeling catalyzed by promiscuous enzymes,such as APEX2,has emerged as a powerful approach to characterize multiprotein complexes and protein-protein interactions.How-ever,current methods depend on the expression of exogenous fusion proteins and cannot be applied to identify proteins surrounding post-translationally modified proteins.To address this limitation,we developed a new method to label proximal proteins of interest by antibody-mediated protein A-ascorbate peroxidase 2(pA-APEX2)labeling(AMAPEX).In this method,a modified protein is bound in situ by a specific antibody,which then tethers a pA-APEX2 fusion protein.Activation of APEX2 labels the nearby proteins with biotin;the biotinylated proteins are then purified using streptavidin beads and identified by mass spectrometry.We demonstrated the utility of this approach by profiling the proximal proteins of histone modifications including H3K27me3,H3K9me3,H3K4me3,H4K5ac,and H4K12ac,as well as verifying the co-localization of these iden-tified proteins with bait proteins by published ChIP-seq analysis and nucleosome immunoprecipi-tation.Overall,AMAPEX is an efficient method to identify proteins that are proximal to modified histones.

OBJECTIVE：To overview the systematic review on the effectiveness of indomethacin in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis （PEP），and to provide reliable evidence-based reference for the prevention of PEP. METHODS ：Retrieved from PubMed ，the Cochrane Library ，Embase，CBM，CNKI，Wanfang database and VIP，systematic review on indomethacin in the prevention of PEP were collected during the inception to Nov. 2020. The methodological quality ，report quality and evidence quality of the included studies were evaluated by AMSTAR 2 scale，PRISMA statement and GRADE method. The effectiveness of PEP prevention was described. RESULTS ：Finally，23 systematic reviews were obtained ，including 12 in Chinese and 11 in English. Tweenty-two systematic reviews showed that compared with placebo ， indomethacin could effectively reduce the incidence of PEP. Eight systematic reviews showed that indomethacin significantly reduced the incidence of moderate and severe PEP compared with placebo. Five systematic reviews showed that indomethacin could reduce the incidence of postoperative hyperamylasemia compared with placebo. Three systematic reviews showed that indomethacin also had a good preventive effect on people with high risk of PEP. PRISMA score of included systematic reviews ranged from 15 to 25. The quality evaluation of AMSTAR 2 methodology included in systematic reviews was low ，and the key items of complete report were 4，9，11 and 13. The GRADE evidence quality evaluation of the included systematic reviews showed that the quality of the evidence was concentrated in the low level. CONCLUSIONS ：Indomethacin has a certain effect in the prevention of PEP ，but the overall evidence quality of the included literatures is generally not high. It needs to be further validated by high-quality clinical research.

Objective:To evaluate the effectiveness and safety of pancreatic duct stent under endoscopic retrograde cholangiopancreatography (ERCP) in the treatment of patients with hypertriglyceridemic pancreatitis (HTGP).Methods:The clinical data of 66 patients with HTGP at the General Hospital of Ningxia Medical University from January 1, 2017 to June 1, 2020 were retrospectively analyzed. The patients were divided into two groups according to treatment methods: conservative group ( n=46) and stent group ( n=20). The incidence of complications, the rate of transfer to the intensive care unit (ICU) for intensive treatment, the acute physiology and chronic health evaluation (APACHE) II score at 48 hours after admission, the level of triglycerides, and the application interval of enzyme inhibitor were compared between groups. Results:There were 53 males and 13 females, aged (39.3±9.7) years. There were no deaths in both groups, all 20 patients in the stent group underwent successful pancreatic duct stenting. Compared with before treatment, the level of blood white blood cell, amylase, triglycerides, and APACHE II scores of patients in the conservative group and the stent group were both significantly reduced after treatment ( P<0.05). After treatment, the APACHE II score of stent group patients was significantly lower than that of the conservative group [2.00(2.00, 4.00) vs 4.00(3.00, 5.25), P<0.05]. The length of fasting, hospitalization, and the enzyme inhibitor application of patients in the stent group were significantly lower than conservative group ( P<0.05). The complication rate of the stent group was significantly lower than conservative group [ 10.0% (2/20) vs 41.3% (19/46), P<0.05]. Conclusion:Pancreatic duct stenting can quickly relieve clinical symptoms of HTGP patients, reduce length of hospital stay and improve prognosis, which means it is a safe and effective treatment strategy for HTGP.

Objective To investigate the feasibility and safety of surgical device closure of doubly committed sub-arterial ventricular septal defect via left sub-axillary.Methods A total of 45 patients diagnosed as doubly committed sub-arterial ventricular septal defect (dcVSD) with transthoracic echocardiography (TTE) and transesophageal echocardiography(TEE) were enrolled from June 2014 to August 2016 in Henan Children Heart Center,Henan Provincial People's Hospital.There were 39 males and 6 females,with the mean age of (2.2 ±2.1) years old(0.5-8.0 years),the body weight (13.8 ± 7.1) kg(7.0-34.1 kg),the defect size (4.5 ± 1.0) mm (3.0-8.0 mm).After general anesthesia,the patients were in supine and evaluated by TEE which indicated whether they were fit to closure.Then,they were turned to the right lateral position while this technique was determined.A vertical incision of 2-3 cm was made between the third and the fifth intercostal space and invasion in thoracic space via fourth intercostal space.Puncture was done at the anterior surface of right ventricular outlet tract to build a delivery tract.The occluder was released and the VSD was occluded under transesophageal echocardiography guidance.Results Forty-one patients had a successful surgical dcVSD closure with asymmetric occluders sized (6.0 ± 1.5) mm(4-10 mm).Among 4 failure cases,2 cases (4.4％) were switched to open-heart surgical repair,1 case (2.2％) due to device related aortic regurgitation,the rest 1 case (2.2％) experienced a dislocation of occluder into pulmonary artery and was converted to surgical repair after retrieve of occluder.Trivial residual shunt was detected in 2 cases (4.4％) postoperatively,a spontaneous closure was observed by 1 month follow-up and 3 months follow-ups,respectively.All the patients were discharged 5 to 8 days after the operation.With a follow-up of (10.4 ±5.0) months [3-24 months],there were no complications such as pericardial effusion,displacement of device,atrioventricular block or new valvular dysfunction.Conclusions Minimally invasive device closure of doubly committed sub-arterial ventricular septal defect via left sub-axillary is a feasible and safe treatment for closure of dcVSD.This technique has advantages of minor wound,less exudation,covert incision,however,long term follow-up is necessary.