BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

ObjectiveTo observe the effects of electroacupuncture at Zhongwan （CV12） on gastric nociceptive response induced by gastric acid stimulation and explore the underlying mechanisms associated with nuclei of the medullary viscerosensory and visceral motor neurons. MethodsTwenty SD rats were given intragastric administration of 0.5 mol/L diluted hydrochloric acid （0.5 ml/100 g） to induce gastric nociceptive response induction. Eight rats were randomly selected to record the gastric slow wave （GSW） area under the curve， and extracellular discharge frequency of neurons in the nucleus of the solitary tract （NTS） and dorsal motor nucleus of the vagus nerve （DMV） before intragastric administration and at 1， 5， 10， 15， 20， 25， 30， 35， 40， 45， 50， 55， and 60 minutes after intragastric administration. The remaining 12 rats received electroacupuncture intervention at Zhongwan within 5 to 25 minutes after intragastric administration of diluted hydrochloric acid， with a duration of one minute. The GSW area under the curve and extracellular discharge frequency of NTS and DMV neurons were compared between the 1-minute intervals before and after electroacupuncture intervention. ResultsCompared to the baseline before intragastric administration， the area under the curve of GSW significantly increased at 1， 5， 10， 15， 20， and 25 minutes after intragastric administration， and the extracellular discharge frequency of excitatory neurons in the NTS （accounting for 90%， 57/63） significantly increased at 1， 5， 10， 15， 20， 25， 30， 35， and 40 minutes， both reaching peak values at 1 minute after intragastric administration （P＜0.01 or P＜0.05）. The extracellular discharge frequency of inhibitory neurons in the DMV （accounting for 91%， 20/22） showed a non-significant increase at 1 minute after intragastric administration （P＞0.05）， but significantly decreased at other timepoints （P＜0.05）. Compared to the baseline before electroacupuncture intervention， the GSW area under the curve and the extracellular discharge frequency of excitatory neurons in the NTS significantly decreased （P＜0.05）， while the extracellular discharge frequency of inhibitory neurons in the DMV showed no significant difference （P＞0.05）. ConclusionElectroacupuncture at Zhongwan can improve gastric nociceptive response induced by gastric acid stimulation， possibly by reducing the transmission of visceral sensation and decreasing the excitability of NTS neurons in the medulla.

The eutR gene deletion mutant of Salmonella enteritidis was successfully constructed by homologous recombination.Through the study of its biochemical characteristics,motility,resist-ance to stress in vitro and survival ability in RAW 264.7 cells,it was found that the biochemical characteristics and motility of the eutR gene deletion mutant of Salmonella enteritidis had no sig-nificant change compared with the wild type of Salmonella enteritidis.The ability of eutR gene de-letion strain of Salmonella enteritidis to resist acid,alkali and oxidation was significantly reduced,while the ability to resist heat was not significantly changed;the survival ability of eutR gene dele-tion strain in RAW 264.7 cells was significantly reduced compared with the wild type.In order to further analyze the effect of eutR gene on the expression of virulence factors of Salmonella enterit-idis,the relative expression levels of invH,ssav,ssrA,xthA,orf245,sodC,lrp,mrr1 and hflk virulence genes of the deletion strain and the wild strain were detected by SYBR Green PCR.It was found that the expression of the virulence factors mentioned above in the eutR gene deletion strain of Salmonella enteritidis was significantly down-regulated compared with that in the wild-type strain.The LD50 of the eutR gene-deleted strain of Salmonella enteritidis was determined by ani-mal experiments,and the results showed that the LD50 of the eutR gene-deleted strain was higher than that of the wild-type strain,indicating that the eutR gene could affect the virulence of Salmonella.This study clarified the effect of eutR gene on the survival ability,some biological characteristics and virulence of Salmonella enteritidis in macrophages,and provided a new gene knockout target for the development of attenuated Salmonella enteritidis genetic engineering vac-cine.

Objective:To evaluate inflammation early in the infarct zone and its dynamic changes after acute myocardial infarction (AMI) using 18F-FDG PET imaging, and analyze its relationship with left ventricular remodeling progression (LVRP). Methods:Sixteen Bama miniature pigs (4-6 months old, 8 females) were selected. AMI models were established by balloon occlusion of the left anterior descending artery. 18F-FDG PET imaging was performed before AMI and at days 1, 5, 8, and 14 post-AMI to evaluate the regional inflammation response. 18F-FDG SUV ratio (SUVR) and the percentage of uptake area of left ventricle (F-extent) in the infarct zone, and the SUVRs of the spleen and bone marrow, were measured. Echocardiography and 99Tc m-methoxyisobutylisonitrile(MIBI) SPECT myocardial perfusion imaging (MPI) were performed at the above time points and on day 28 post-AMI to assess left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and myocardial perfusion defect extent. The degree of LVRP at day 28 post-AMI was defined as ΔLVESV(%)=(LVESV AMI 28 d-LVESV AMI 1 d)/LVESV AMI 1 d×100%. Data were analyzed using repeated measures analysis of variance, Kruskal-Wallis rank sum test and Pearson correlation analysis. Results:Twelve pigs were successfully modeled and completed the study. Inflammation in the infarct zone persisted until day 14 post-AMI. The SUVR of the infarct zone pre-AMI and at days 1, 5, 8, and 14 post-AMI were 1.03±0.08, 3.49±1.06, 2.93±0.90, 2.38±0.76, and 1.63±0.62, respectively ( F=49.31, P<0.001). The F-extent values in the infarct zone pre-AMI and at days 1, 5, 8, and 14 post-AMI were 0, (40.08±12.46)%, (40.00±12.76)%, (31.08±12.82)%, and 16.50%(7.25%, 22.00%), respectively ( H=37.61, P=0.001). There were no significant differences in the SUVRs of bone marrow and spleen before and after AMI ( F values: 0.69 and 0.77, both P>0.05). At day 1 post-AMI, both SUVR and F-extent in the infarct zone were significantly correlated with LVRP ( r values: 0.82 and 0.70, P values: 0.001 and 0.035). Conclusions:18F-FDG PET imaging can be used to evaluate inflammation in the infarct area and its dynamic changes after AMI. Inflammation in the infarct area is severe at day 1, and then gradually decreases. The extent and severity of inflammation visible on 18F-FDG PET imaging 1 d after AMI are closely related to LVRP.

OBJECTIVE To evaluate the effectiveness， safety， economy， innovation， suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein （EC）， and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin （TB-PPD） were analyzed by the method of systematic review. Cost minimization analysis， cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD， and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation， suitability and accessibility were determined by systematic review and improved Delphi expert consultation， and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness， safety， economy， innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent， while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight， the scores of effectiveness， safety， economy， innovation， suitability， accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD， EC performs better in all dimensions of effectiveness， safety， economy， innovation， suitability and accessibility. However， it is worth noting that EC should further improve its availability in the dimension of accessibility.

Objective:To investigate the characteristics, process, and prognosis of esophageal stricture after circumferential endoscopic submucosal dissection (ESD), and to preliminarily analyze the prevention and treatment effects of simple dilation, stent placement, mucosal transplantation, and glucocorticoid (hereinafter referred to as hormone) application in esophageal stricture.Methods:From August 2017 to March 2022, at the First Affiliated Hospital of Zhengzhou University, the clinical and follow-up data of 55 patients who underwent circumferential ESD for early esophageal cancer and precancerous lesions were retrospectively analyzed. According to the prevention and treatment methods for esophageal stricture, the patients were divided into two groups: simple dilation group (23 cases) and combined dilation group (32 cases). The combined dilation group was divided into mucosal transplantation subgroup (9 cases), stent placement subgroup (14 cases), hormone application subgroup (7 cases), and bleomycin subgroup (2 cases, excluded from comparative analysis due to limited cases). Overall prognosis of patients was observed. Treatment efficacy, prognosis, and adverse events were compared among the simple dilation group, mucosal transplantation subgroup, stent placement subgroup, and hormone application subgroup. Independent samples t-test, chi-square test, and Fisher′s exact test were used for statistical analysis. Results:Among the 55 patients, the follow-up time was (894.1±417.7) days. Refractory esophageal stricture (total dilation times ≥ 5) occurred in 33 patients (60.0%). Fifty-two patients (94.5%) achieved clinical remission of the stricture. The total number of dilations was 5.8±4.0, and the average dysphagia-free period was (52.3±37.1) days. The dysphagia-free period of mucosal transplantation subgroup was longer than that of the simple dilation group, stent placement subgroup, and hormone application subgroup ((114.5±50.0) days vs. (40.9±20.0), (39.7±10.0), and (40.9±25.5) days, respectively), and the differences were statistically significant ( t=4.82, 3.77 and 3.14, P<0.001, =0.011, =0.009). There were no statistically significant differences between the simple dilation group and the mucosal transplantation subgroup, stent placement subgroup, and hormone application subgroup in the total number of dilations (6.8±4.8 vs. 3.0±2.5, 5.8±2.2, and 5.7±5.0), stricture remission rate (95.7%, 22/23 vs. 8/9, 13/14, and 7/7), and incidence of adverse events (17.4%, 4/23 vs. 5/9, 5/14, and 2/7; all P>0.05). Conclusions:Esophageal stricture formed after circumferential ESD shows the characteristics of recurrence and intractability. The over all number of dilations is high, and the average dysphagia-free period is short. Most patients can achieve clinical remission of the stricture after multiple times of endoscopic dilation treatment. However mucosal transplantation, stent placement, and hormone application cannot well intervene the natural process of esophageal stricture.

Objective:To analyze the clinical and laboratory characteristics of acute myeloid leukemia (AML) patients with NPM1 mutation, and to explore the prognostic factors.Methods:A total of 77 AML patients with NPM1 gene mutation admitted to Hebei Yanda Ludaopei Hospital from May 1st 2012 to December 31st 2021 were enrolled in the study, including 34 male and 43 female patients. The median age was 40 (3, 68) years old. Patients were selected and divided into 4 groups according to the morphological FAB classification. There were 29 cases (37.7%) of M1 type, 13 cases (16.9%) of M2 type, 23 cases (29.9%) of M4 type, and 12 cases (15.5%) of M5 type. The clinical characteristics, bone marrow/peripheral blood cell morphology, immunophenotype, cytogenetics, molecular biology and overall survival of different groups were retrospectively analyzed, and the risk factors affecting the prognosis of AML were also explored. Cox multivariate regression was used to analyze the clinical influencing factors of survival and prognosis.Results:The white blood cell counts were highest in M4 and M5 patients and lowest in M2 patients, while no significant difference in the red blood cell, hemoglobin, and platelet counts( P>0.05). Morphologically, there were significant differences in the percentage of blasts and blasts with cup-like nuclei on bone marrow (BM) and peripheral blood (PB). The proportion of blasts in BM and PB was the highest in M1 and the lowest in M2 ( P<0.001). The positive rate of blasts with cup-like nuclei was the highest in M1 and the lowest in M5 of BM ( P<0.001), while the highest in M2 and the lowest in M5 of PB ( P=0.006). The scores of myeloperoxidase and chloroacetate esterase were all the highest in M1 and the lowest in M5 ( P<0.001, 0.001, respectively). In terms of molecular biology, the occurence rate of blasts combined with DNMT3A mutation was the highest in M4 and the lowest in M2 ( P=0.044), while those combined with FLT3-ITD mutation was the highest in M4 and the lowest in M5 ( P=0.002). In immunophenotype, there were significant differences in the expression positivities of seven antigens including HLA-DR, CD56, CD11c, CD15, CD14, CD96 and cMPO ( P<0.05). Multivariate COX regression analysis showed that no recurrence after treatment ( P<0.001), complete remission after treatment ( P=0.015) and transplantation ( P<0.001) were correlated with overall survival (OS). No recurrence after treatment ( P=0.033), transplantation ( P=0.027), no mutation of FLT3-ITD ( P=0.040), and hemoglobin concentration ( P=0.023) were associated with relapse-free survival (RFS). Survival analysis by Kaplan-Meier curve showed that there was no significant difference in survival time between the M1, M2, M4 and M5 groups in OS and RFS. Conclusion:There were significant differences in the white blood count, the percentage of blasts and blasts with cup-like nuclear morphology, cytochemical staining (MPO integration, CE integration and percentage of NAS-DCE), gene mutation (DNMT3A and FLT3-ITD) and immunophenotypes (HLA-DR, CD56, CD11c, CD15, CD14, CD96 and cMPO) between the four groups. The multivariate analysis revealed that no recurrence after treatment and transplantation were independent prognostic factors in NPM1 mut AML patients. On the other hand, FLT3-ITD mutation and hemoglobin concentration were associated with RFS and complete remission after treatment was associated with OS in the entire NPM1 mut cohort.

OBJECTIVE To evaluate the quality of research literature on pharmacoeconomics of traditional Chinese medicine （TCM） in China from 2018 to 2022， to understand the development status and problems of TCM pharmacoeconomic research in China， and to provide a reference for future standardized research on this field. METHODS The systematic search of relevant databases at home and abroad was conducted to obtain the published literature on TCM pharmacoeconomic research in China from January 1， 2018 to November 21， 2022 to summarize the basic information of the literature， the research profile， the method and content of pharmacoeconomic evaluation and to evaluate the quality of the literature by using the CHEERS 2022 checklist； calculate the total literature score by counting the scores of the specific entries of each piece of literature and classifying the quality of the literature as excellent， good， qualified， and unqualified. RESULTS A total of 71 studies were included， involving 60 in Chinese and 11 in English， and 53.52% of the literature was supported by grants； the most studied TCM dosage form was injection （31.03%）； less than half （46.48%） of the literature reported the study angle； short-term economic evaluation was predominantly used （69.01%）； the Chinese studies were dominated by cost-effectiveness analyses （70.00%）， and the English studies were dominated by cost-utility analysis （54.55%）. The average score of literature quality evaluation was 11.02， with two （2.82%） of the literature being of good quality， nine （12.68%） of the literature being of qualified quality， and the majority of the literature （84.51%） being of unqualified quality. The average score of Chinese literature was 9.98， and the average score of English literature was 16.73， with the quality of the latter being significantly better than that of the former. CONCLUSIONS At present， the pharmacoeconomic researches of TCM mainly has problems such as lack of scientific selection of intervention in the control group， nonstandard cost measurement， unreasonable selection of research time limit， quality of evidence for health output indicators to be improved， selection of evaluation methods to be improved， and lack of scientific basis for threshold selection. In order to support the implementation and development of high-level pharmacoeconomics research on TCM， policymakers need to create a favorable policy environment and formulate pharmacoeconomic evaluation guidelines that meet the characteristics of TCM， so as to promote the application and transformation of evaluation results.

ObjectiveTo clarify the development and methodological research status of clinical comprehensive evaluation of Chinese patent medicines in China and identify the problems and difficulties in the evaluation， so as to provide a reference for promoting the subsequent evaluation. MethodFirstly， we analyzed the current situation of clinical comprehensive evaluation in China by reviewing the articles about the process of clinical comprehensive evaluation of drugs and the process of clinical comprehensive evaluation of Chinese patent medicines. Secondly， we comprehensively summarized the formulation background and key points of policies related to clinical comprehensive evaluation of Chinese patent medicines and then show the development status in this field at the national and provincial levels. ResultThe comprehensive clinical evaluation of Chinese patent medicines is still in its infancy in China， and 32 articles of specific evaluation of Chinese patent medicines were included in the study. The dosage forms were mainly capsules （15 articles， 46.88%） and injections （28.13%）. The evaluation mainly involved diseases such as the nervous system （10 articles， 31.25%）， digestive system （5 articles， 15.63%）， and respiratory system （5 articles， 15.63%）. The research results of clinical comprehensive evaluation of Chinese patent medicines were mainly from relevant societies and research institutions. Different research teams have developed technical guidelines or specifications for the evaluation， while the government-leading evaluation guidelines remained to be formulated at the national and provincial levels. In addition， the research articles in this field mainly concentrated on the application of evaluation methods， the building of evaluation index systems， and completed evaluation reports. ConclusionTo reflect the unique value and advantages of Chinese patent medicines， the government needs to build technical guidelines for the clinical comprehensive evaluation of Chinese patent medicines on the basis of the clinical comprehensive evaluation of drugs and create a favorable policy environment for the evaluation work.

Objective:To evaluate the left ventricular diastolic dyssynchrony (LVDD) and its influencing factors early after acute myocardial infarction (AMI) using phase analysis of SPECT gated myocardial perfusion imaging (GMPI).Methods:Bama miniature swines ( n=16) were subjected to establish AMI models. GMPI was performed before and 1 d after AMI to obtain the extent of myocardial perfusion defect (Extent, %) and left ventricular systolic dyssynchrony (LVSD)/LVDD parameters, namely the phase histogram bandwidth (PBW) and phase standard deviation (PSD). Meanwhile, left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and the ratio of early to late peak mitral diastolic flow (E/A) were obtained by echocardiography. Independent-sample t test, paired t test and Pearson correlation analysis were used to analyze the data. Results:Sixteen AMI swines were successfully created. Compared to baseline, Extent, LVEDV and LVESV significantly increased on 1 d after AMI ( t values: -11.14, -4.55, -6.12, all P<0.001), while LVEF and E/A significantly decreased ( t values: 10.16, 2.18, P<0.001, P=0.046). GMPI showed that the LVDD parameters PBW and PSD increased significantly on 1 d after AMI when compared to those at baseline((142.25±72.06)° vs (33.06±8.98)°, (56.15±26.71)° vs (12.51±5.13)°; t values: -6.11, -6.60, both P<0.001). There were significant differences between LVSD parameters and LVDD parameters (PBW: (109.06±62.40)° vs (142.25±72.06)°, PSD: (44.40±25.61)° vs (56.15±26.71)°; t values: -2.73, -2.20, P values: 0.016, 0.044). LVDD parameters PBW, PSD were negatively correlated with E/A after AMI ( r values: -0.569, -0.566, P values: 0.021, 0.022), and positively correlated with the Extent ( r values: 0.717, 0.634, P values: 0.002, 0.008). The phase analysis of SPECT GMPI to evaluate LVDD showed good intra-observer and inter-observe reproducibility (intraclass correlation coefficient (ICC): 0.953-0.984, all P<0.001). Conclusions:LVDD occurs early on 1 d after AMI, and can reflect left ventricular diastolic dysfunction. The Extent is correlated with LVDD significantly. Phase analysis of SPECT GMPI is an accurate method to evaluate LVDD and left ventricular diastolic function.