BACKGROUND:Allogeneic hematopoietic stem cell transplantation is an important treatment for malignant hematological diseases,and delayed postoperative platelet implantation is a common complication that seriously affects the quality of patient survival;however,there are no standard protocols to improve platelet implantation rates and prevent platelet implantation delays. OBJECTIVE:To compare the safety and efficacy of oral Herombopag Olamine versus subcutaneous recombinant human thrombopoietin for promoting platelet implantation in patients with malignant hematological diseases undergoing haploid hematopoietic stem cell transplantation. METHODS:Clinical data of 163 patients with malignant hematological diseases who underwent haploidentical hematopoietic stem cell transplantation from January 2016 to October 2022 were retrospectively analyzed.A total of 72 patients who started to subcutaneously inject recombinant human thrombopoietin at+2 days were categorized into the recombinant human thrombopoietin group;a total of 27 patients who started to orally take Herombopag Olamine at+2 days were categorized into the Herombopag Olamine group;and 64 patients who did not apply Herombopag Olamine or recombinant human thrombopoietin were categorized into the blank control group.The implantation status,incidence of acute graft-versus-host disease of degree II-IV within 100 days,1-year survival rate,1-year recurrence rate,and safety were analyzed in the three groups. RESULTS AND CONCLUSION:(1)The average follow-up time was 52(12-87)months.The implantation time of neutrophils in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group was(12.95±3.88)days,(14.04±3.71)days,and(13.89±2.74)days,respectively,with no statistically significant difference(P=0.352);the implantation time of platelets was(15.16±6.27)days,(17.67±6.52)days,and(17.00±4.75)days,with no statistically significant difference(P=0.287).(2)The complete platelet implantation rate on day 60 was 64.06%,90.28%,and 92.59%,respectively,and the difference was statistically significant(P<0.001).The subgroup analysis showed that the difference between the blank control group and the recombinant human thrombopoietin group was statistically significant(P<0.001),and the difference between the blank control group and the Herombopag Olamine group was statistically significant(P=0.004).The difference was not statistically significant between the recombinant human thrombopoietin group and Herombopag Olamine group(P=0.535).(3)100-day II-IV degree acute graft-versus-host disease incidence in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group were 25.00%,30.56%,and 25.93%,respectively,and the difference was not statistically significant(P=0.752).(4)The incidence of cytomegalovirus anemia,cytomegalovirus pneumonia,and hepatic function injury had no statistical difference among the three groups(P>0.05).(5)During the follow-up period,there was no thrombotic event in any of the three groups of patients.(6)The results showed that recombinant human thrombopoietin and Herombopag Olamine could improve the platelet implantation rate of malignant hematological disease patients after haploidentical hematopoietic stem cell transplantation,with comparable efficacy and good safety.

ObjectiveTo analyze the expression level of triggering receptor expressed on myeloid cells-1 （TREM-1） in serum and ascites of patients with cirrhotic ascites， and to investigate its correlation with clinical features and inflammatory markers and its role in the diagnosis of infection and prognostic evaluation. MethodsA total of 110 patients with cirrhotic ascites who were hospitalized in The Fifth Hospital of Shijiazhuang from January 2019 to December 2020 were enrolled， and according to the presence or absence of intra-abdominal infection， they were divided into infection group with 72 patients and non-infection group with 38 patients. The patients with infection were further divided into improvement group with 38 patients and non-improvement group with 34 patients. Clinical data and laboratory markers were collected from all patients. Serum and ascites samples were collected， and ELISA was used to measure the level of TREM-1. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups； the chi-square test was used for comparison of categorical data between two groups. A Spearman correlation analysis was used to investigate the correlation between indicators. A multivariate Logistic regression analysis was used to identify the influencing factors for the prognosis of patients with cirrhotic ascites and infection. The receiver operating characteristic （ROC） curve was used to evaluate the diagnostic and prognostic efficacy of each indicator， and the Delong test was used for comparison of the area under the ROC curve （AUC）. ResultsThe level of TREM-1 in ascites was significantly positively correlated with that in serum （r=0.50， P<0.001）. Compared with the improvement group， the non-improvement group had a significantly higher level of TREM-1 in ascites （Z=-2.391， P=0.017） and serum （Z=-2.544， P=0.011）， and compared with the non-infection group， the infection group had a significantly higher level of TREM-1 in ascites （Z=-3.420， P<0.001）， while there was no significant difference in the level of TREM-1 in serum between the two groups （P>0.05）. The level of TREM-1 in serum and ascites were significantly positively correlated with C-reactive protein （CRP）， procalcitonin （PCT）， white blood cell count， and neutrophil-lymphocyte ratio （r=0.288， 0.344， 0.530， 0.510， 0.534， 0.454， 0.330， and 0.404， all P<0.05）. The ROC curve analysis showed that when PCT， CRP， and serum or ascitic TREM-1 were used in combination for the diagnosis of cirrhotic ascites with infection， the AUCs were 0.715 and 0.740， respectively. The multivariate Logistic regression analysis showed that CRP （odds ratio ［OR］=1.019， 95% confidence interval ［CI］： 1.001‍ ‍—‍ ‍1.038， P=0.043） and serum TREM-1 （OR=1.002， 95%CI： 1.000‍ ‍—‍ ‍1.003， P=0.016） were independent risk factors for the prognosis of patients with cirrhotic ascites and infection， and the combination of these two indicators had an AUC of 0.728 in predicting poor prognosis. ConclusionThe level of TREM-1 is closely associated with the severity of infection and prognosis in patients with cirrhotic ascites， and combined measurement of TREM-1 and CRP/PCT can improve the diagnostic accuracy of infection and provide support for prognostic evaluation.

Tripterygium wilfordii polyglycosides are one of the most commonly used Tripterygium wilfordii preparations， which have anti-inflammatory and immune-regulating effects. Their unique therapeutic effect on some autoimmune diseases and kidney diseases is almost irreplaceable by other similar drugs， but the possible reproductive damage is the bottleneck that hinders their clinical application. In clinical use， female patients often suffer from menstrual cycle disorders， decreased menstrual flow， even amenorrhea， infertility， and other symptoms， and the main toxic mechanism lies in damaging the reproductive and endocrine functions of the ovary and inhibiting the growth and development of follicles. Therefore， it is particularly necessary to understand the toxic and side effects of Tripterygium wilfordii polyglycosides on female reproduction and master the detoxification methods during clinical use. However， there is no clear solution to these problems. According to the theory of traditional Chinese medicine， "kidney governs reproduction"， and the relationship between kidney Yin， kidney essence， and female ovum is close. Therefore， by considering that the damage to the reproductive system caused by Tripterygium wilfordii polyglycosides belongs to the category of kidney deficiency， Yin damage， and essence deficiency， the "strengthening kidney Yin" method is proposed. It points out that the reproductive toxicity damage of Tripterygium wilfordii polyglycosides on the female can be effectively alleviated by tonifying kidney and Yin essence in clinical use. The relevant research on traditional Chinese medicine， classical prescription， test prescription， and acupuncture is summarized to verify the necessity of the "strengthening kidney Yin" method， so as to provide a theoretical basis for the safe and rational clinical use of Tripterygium wilfordii.

BACKGROUND:HLA haploid allogeneic hematopoietic stem cell transplantation provides a chance of survival for patients with high-risk hematologic malignancies.In recent years,the research on the transplantation mode and graft selection of haploidentical transplantation is still ongoing.At present,the mixed transplantation model of non-extracorporeal T-cell removal bone marrow and peripheral blood stem cells established by the Hematology Research Center of Peking University is gradually becoming popular in China,but this model requires the collection of donor bone marrow fluid,which increases the pain and risk of the donor. OBJECTIVE:To explore the curative effect of infusion of umbilical cord mesenchymal stem cells replacing donor bone marrow cells in haploidentical peripheral blood hematopoietic stem cell transplantation for malignant hematological diseases. METHODS:Fifty hematological malignancies patients who underwent haploidentical hematopoietic stem cell transplantation from January 2019 to May 2022 were selected and randomly assigned to two study groups at a ratio of 2:3.Among them,19 patients received umbilical cord mesenchymal stem cell combined with peripheral blood stem cell transplantation,and 31 patients were treated with bone marrow cells combined with peripheral blood stem cells.The study was approved by the Ethics Committee of Henan Provincial People's Hospital.The recipients of umbilical cord mesenchymal stem cells were first transfused with third-party umbilical cord mesenchymal stem cells(1×106/kg)on the day of transplantation,followed by peripheral blood hematopoietic stem cells 6 hours later.In the bone marrow group,donor bone marrow cells were transfused +1 day after transplantation and peripheral blood stem cells were transfused +2 days after transplantation.After transplantation,rabbit anti-human thymocyte immunoglobulin,cyclosporine A,mycophenolate mofetil,and a short-course methotrexate were used for graft-versus-host disease prophylaxis for all recipients. RESULTS AND CONCLUSION:No adverse events occurred during the reinfusion of umbilical cord mesenchymal stem cells.There were no significant differences between the mesenchymal stem cell group and the bone marrow group in the engraftment rate[100%(19/19)vs.96.8%(30/31),P>0.05],median duration for neutrophil engraftment(14 days vs.15 days,P>0.05)and median duration for platelet engraftment(20 days vs.19 days,P>0.05).The incidence of grade Ⅱ-Ⅳ acute graft-versus-host disease in the mesenchymal stem cell group was significantly lower than in the bone marrow group[21.1%(4/19)vs.58.1%(18/31),P = 0.01].There were no significant differences between the two groups in the incidence of chronic graft-versus-host disease[21.1%(4/19)vs.25.8%(8/31),P>0.05],the relapse rates[15.8%(3/19)vs.16.1%(5/31),P>0.05]and the incidence of early cytomegalovirus viremia[42.1%(8/19)vs.35.5%(11/31),P>0.05],and the 2-year overall survival rate[68.4%(10/19)vs.70.9%(16/31),P>0.05].It is indicated that umbilical cord mesenchymal stem cells replace donor bone marrow cells in haploidentical peripheral blood stem cell transplantation for malignant hematological diseases,which reduced the incidence of acute graft-versus-host disease after transplantation,did not increase the incidence of chronic graft-versus-host disease,recurrence rate and early cytomegalovirus viremia,and reduced the pain and risk of donor pulp extraction.

Microplastics(MPs)and nanoplastics(NPs)have become hazardous materials due to the massive amount of plastic waste and disposable masks,but their specific health effects remain uncertain.In this study,fluorescence-labeled polystyrene NPs(PS-NPs)were injected into the circulatory systems of mice to determine the distribution and potential toxic effects of NPs in vivo.Interestingly,whole-body imaging found that PS-NPs accumulated in the testes of mice.Therefore,the toxic effects of PS-NPs on the reproduction systems and the spermatocytes cell line of male mice,and their mechanisms,were investigated.After oral exposure to PS-NPs,their spermatogenesis was affected and the spermatogenic cells were damaged.The spermatocyte cell line GC-2 was exposed to PS-NPs and analyzed using RNA sequencing(RNA-seq)to determine the toxic mechanisms;a ferroptosis pathway was found after PS-NP exposure.The phenomena and indicators of ferroptosis were then determined and verified by ferroptosis inhibitor ferrostatin-1(Fer-1),and it was also found that nuclear factor erythroid 2-related factor 2(Nrf2)played an important role in spermatogenic cell ferroptosis induced by PS-NPs.Finally,it was confirmed in vivo that this mechanism of Nrf2 played a protective role in PS-NPs-induced male reproductive toxicity.This study demonstrated that PS-NPs induce male reproductive dysfunction in mice by causing spermatogenic cell ferroptosis dependent on Nrf2.

Radiotherapy is an important means to treat lung cancer,but it is easy to cause lung injury and reduce the quality of life of patients.Flash radiotherapy(FLASH-RT)has attracted attention due to its extremely short radiation duration and high dose rate,which can reduce toxicity of normal tissue while ensures treatment intensity of tumor.Whether Flash-RT can reduce radiation-induced lung injury has become an important research topic in recent years.Based on the literature analysis method,this review systematically assessed the effects and mechanisms of Flash-RT and radiotherapy with conventional dose rate on lung injury through searching relevant literatures at home and abroad,so as to provide scientific basis for the treatment of patients with lung cancer by reviewing the comparisons about the effects and mechanisms between Flash-RT and radiotherapy with conventional dose rate on lung injury.Compared with radiotherapy with conventional radiation rate,Flash-RT can significantly reduce lung injury and improve quality of life of patients.It is still demanded to explore the Flash-RT mechanism in future,so as to develop the Flash-RT instrument that is suitable for different tumors and to conduct larger-scale clinical researches.

Objective:To investigate the influence of changes in the cognitive load of anesthesia residents on the teaching effectiveness of high-fidelity scenario simulation.Methods:Eighty-seven anesthesia residents in a grade-A tertiary hospital from February to November 2022 were divided into groups A, B, and C according to the random number method. Three cases were selected from the anesthesia crisis resource teaching case library for high-fidelity simulation training for the three groups, respectively, using the crossover design to control the order of the cases. Each round of training consisted of pre-training instruction, simulation teaching, and post-training summarization and analysis. After three rounds of simulation teaching, cognitive load, anxiety status, test scores, and non-technical skills were evaluated for all the study participants. SPSS 20.0 was used to perform analysis of variance with repeated measures and Pearson's correlation analysis.Results:All the three groups showed significantly higher cognitive load and anxiety scores during the first-round simulation training than during the second-round and third-round simulation trianing. The test scores were significantly lower in the first round [(87.07±5.66), (88.38±5.41), (89.07±6.17)] than in the second round [(95.69±2.29), (96.10±2.08), (96.07±2.60)] and the third round [(96.34±1.45), (96.38±1.50), (96.17±1.73); all P<0.05]. The non-technical skill scores were also significantly lower in the first round [(37.24±7.58), (38.69±7.27), (39.24±8.74)] than in the second round [(46.17±5.55), (47.07±5.59), (47.59±6.74)] and the third round [(47.17±5.21), (48.48±5.38), (48.24±6.83); all P<0.05]. For simulations with the same cases, the trainees showed significantly higher cognitive load and anxiety scores and significantly lower test scores and non-technical skill scores in the first round than in the second and third rounds ( P<0.05). Conclusions:Anesthesia residents have higher levels of cognitive load and anxiety in the first scenario simulation training, which can reduce learning outcomes, and repeated simulation training can reduce trainees' cognitive load and anxiety.

Objective To observe the value of machine learning model for predicting the risk of dementia in patients with depression.Methods Totally 31 587 depression patients from UK Biobank database were retrospectively enrolled and divided into dementia group(n=896)or non-dementia group(n=30 691)based on follow-up data showed developed dementia or not,also divided into training set(n=18 952)or test set(n=12 635)at the ratio of 6:4.Based on interviews and questionnaire surveys,a total of 190 factors including demographic characteristics,lifestyle,health status,physical indicators and imaging data were included and screened to establish models with light gradient boosting machine(LightGBM),ridge regression(Ridge)and adaptive boosting(AdaBoost),and the value for predicting the risk of dementia in patients with depression was observed.Results A total of 10 factors were ultimately enrolled,including age,waist circumference,employment status,daytime rest,daytime doze or drowsiness,duration of mobile phone use,number of family members,duration of depression,guilt and seeking medical attention due to psychological issues.Based on the above factors,the models were established.In training set,the area under the curve(AUC)of LightGBM,Ridge and AdaBoost model for predicting dementia risk in patients with depression was 0.914,0.832 and 0.889,respectively,and the differences between each 2 models were significant(all P＜0.05);while in test set,the AUC was 0.866,0.842 and 0.859,respectively,except for LightGBM and AdaBoost,the other with significant differences between each two(both P＜0.05).The calibration curve showed that the LightGBM model had the best fit.Conclusion LightGBM machine learning model was helpful for predicting the risk of dementia in patients with depression.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.