[Objective] To investigate the molecular prevalence and genotype of human parvovirus B19(B19) among blood donors in Lanzhou, and provide data support for monitoring the positive rate of B19 DNA in local blood donors. [Methods] A total of 7 644 blood donor samples collected from January to September 2022 were randomly screened using real-time fluorescent PCR, resulting in 23 samples testing positive for B19 DNA. The characteristics of the B19 DNA reactive donors including gender, age, blood donation recruitment and promotion mode, and donation frequency were analyzed using SPSS 22.0. Additionally, the VP1 gene fragment of B19 DNA reactive samples was sequenced and an evolutionary tree was constructed by the N-J method. [Results] The results showed that the positive rate of B19 DNA in Lanzhou was 0.30%, and the positive population mainly consisted of female individuals aged 18-30 years old who were first-time blood donors; furthermore, genotype 1a was identified as predominant. [Conclusion] The positive rate of B19 DNA is low among blood donors in Lanzhou, with genotype 1a being predominant. It is recommended to periodically monitor the B19 prevalence in blood donors and enhance prevention and control measures, thus improving blood quality and safety.

Objective:To investigate alterations in the immune lineage of T-cell large granular lymphocytic leukemia (T-LGLL) at the single-cell transcriptome level and to elucidate its pathogenic mechanisms.Methods:Peripheral blood samples were collected from 5 T-LGLL patients before and after treatment (from June 2019 to December 2020) and 3 healthy controls at the Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC. Single-cell transcriptome sequencing libraries were prepared and sequenced using 10× Genomics technology. Differentially expressed genes in immune cells were compared between patients and healthy donors, followed by pathway enrichment analyses.Results:Profiling 67,237 immune cells revealed that, in T-LGLL: 1) Effector CD8+ T cells exhibited increased numbers, enhanced cytotoxicity, and greater proliferative capacity. Following effective immunosuppressive therapy, both the proliferative capacity and effector functions of these cells significantly decreased ( P<0.05). 2) The proportion of regulatory T (Treg) cells was reduced, accompanied by increased apoptosis. After effective immunosuppressive therapy leading to remission, Treg cell proportions increased, and apoptotic pathways were downregulated ( P<0.05). 3) Antigen-presenting cells (APCs) showed enhanced functionality. Monocytes and dendritic cells were enriched in antigen synthesis and presentation pathways, while B cells displayed increased antigen-binding capacity and were enriched in pathways related to T-cell activation ( P<0.05). 4) Natural killer (NK) cells exhibited attenuated cytotoxic function but demonstrated an enhanced regulatory capacity over T cells ( P<0.05) . Conclusions:T-LGLL patients present a characteristic immunological profile marked by an imbalance in immune homeostasis. This profile includes abnormal activation and expansion of effector CD8 + T cells, and a reduction in Treg cell numbers accompanied by functional impairment. Furthermore, APCs and NK cells were found to positively regulate T-lymphocyte activation, differentiation, and proliferation.

Objective To examine the serological and molecular prevalence as well as genotype characteristics of human Parvovirus B19 blood donors in Lanzhou,and to provide evidence for developing a screening strategy to reduce the risk of blood transfusion transmission.Methods A total of 5 722 blood samples collected from Lanzhou blood donors from April 2023 to October 2023 were tested for B19 DNA using real-time quantitative PCR(qRT-PCR).Additionally,383 samples were screened for anti-B19 IgG and anti-B19 IgM using synchronous enzyme-linked immunoassay(ELISA).Viral load and VP1 sequencing were conducted on the B19 DNA-positive samples and the Neighbor-Joining(N-J)method was used to construct an evolutionary tree for the sequenced samples.Results The prevalence of human Parvovirus B19 DNA,IgG antibody and IgM antibody was 0.47%(27/5 722),25.59%(98/383)and 0.26%(1/383),respectively,and the samples positive for B19 DNA,IgG antibody and IgM antibody were 0.26%(1/383).The co-positivity rate for B19 DNA and IgG antibody was 6.27%(24/383),while the positivity rates for B19 DNA or IgG antibody alone were 0.52%(2/383)and 19.06%(73/383),respectively.Viral loads ranged from 4.24 IU/ml to 5.67×102 IU/ml,all below 104 IU/ml.There was no statistical significance in the positive rate of B19 DNA in gender(χ2=0.86,P=0.35),but there was statistical significance in the positive rate of B19 DNA among all age groups(χ2=8.00,P=0.02).The highest positive rate of B19 DNA was 0.65%in the 18～30 age group.There was statistical significance in the positive rate of B19 IgG antibody in gender(χ2=5.03,P=0.02),but there was no statistical significance in the positive rate of B19 IgG antibody among all age groups(χ2=0.51,P=0.77).The highest positive rate of B19 IgG antibody was 29.09%in the age group of 41 to 60.There was no significant difference in the positive rate of B19 IgM antibody in gender(χ2=2.84,P=0.09).The highest positive rate of B19 IgM was 3.85%in the age group of 18～30 years old.Based on the VP1 sequence,the phylogenetic tree revealed that B19 strains in Lanzhou formed a distinct cladistic lineage within genotype 1,predominantly represented by genotype 1b.Conclusion The prevalence of B19 DNA and IgM antibodies among blood donors in the Lanzhou area is low,and so is the viral load.Therefore the risk of transmitting B19 through blood transfusion is relatively small.Since the prevalence of B19 IgG antibody is high,it is suggested to closely monitor the transmission situation in the area,regularly monitor the prevalence of B19 among blood donors,and track the situation of B19 DNA-positive blood donors to recipients to ensure the safety of clinical blood transfusion.

An increasing number of studies have shown that there is a close relationship between Alzheimer's disease(AD)and diabetes mellitus(DM).Traditional Chinese medicine holds that"kidney yin deficiency"is the common pathogenesis of these two diseases,while modern medicine believes that their pathogenesis involves abnormal aggregation of amyloid proteins,insulin deficiency and resistance,inflammatory response,oxidative stress,and autophagy,among others.The well-known traditional Chinese medicine formula Liuwei Dihuang Pills plays a significant role in the treatment of these two diseases with the same therapeutic approach.Therefore,this article will explore the connection between Liuwei Dihuang Pills and the treatment of AD and DM from different aspects;analyze the common etiology and pathogenesis of AD and DM,and explain the mechanism of prevention and treatment of Liuwei Dihuang Pills,with the aim of providing new ideas and methods for the integrated traditional and Western medicine prevention and treatment of AD and DM in the future.

Objective:To investigate the factors influencing early recurrence for patients with initially unresectable hepatocellular carcinoma (HCC) who underwent salvage liver resection (SLR) following transcatheter arterial chemoembolization-based downstaging treatment, and construct a predictive model to evaluate its predicting performance.Methods:The retrospective cohort study was constructed. The clinicopathological data of 305 patients with initially unresectable HCC who were admitted to 4 medical centers in China, including the Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital) et al, from January 2019 to December 2021 were collected. There were 286 males and 19 females, aged (48.7±10.4)years. A total of 133 patients who were admitted from January 2019 to December 2020 were set as the training cohort, and the other 172 patients who were admitted from January to December 2021 were set as the validation cohort. Observation indicators: (1) postoperative recurrence-free survival in HCC patients; (2) analysis of factors influencing postoperative early recurrence in HCC patients; (3) construction and validation of the predictive model. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the rank sum test. Univariate and multivariate analyses were conducted using the Cox regre-ssion model. The Kaplan-Meier method was used to calculate survival. The Log-rank test was used for survival analysis. The predicting performance of the model was evaluated using the concordance index (C-index) and the area under curve (AUC) of time-dependent receiver operating characteristic (ROC) curve, and the accuracy of the model was validated using the calibration curve. The total net gain of the model was evaluated using the decision curve. Results:(1) Postoperative recurrence-free survival in HCC patients. The recurrence-free survival time of 133 HCC patients in the training cohort was 10.0(range, 1.5-24.0)months, with 1-, 2-year recurrence-free survival rate of 47.3% and 36.8%. The recurrence-free survival time of 172 HCC patients in the validation cohort was 11.0(range, 1.0-24.0)months, with 1-, 2-year recurrence-free survival rate of 51.7% and 37.2%. There was no significant difference in recurrence-free survival between patients in the training cohort and the validation cohort ( χ2=0.075, P>0.05). (2) Analysis of factors influencing postoperative early recur-rence in HCC patients. Results of multivariate analysis showed that tumor burden prior to down-staging treatment, grade of albumin-bilirubin (ALBI) score prior to SLR, alpha-fetoprotein (AFP) half-life prior to SLR, and tumor response prior to SLR were independent factors influencing early recurrence in HCC patients after surgery [ hazard ratio=3.212, 2.526, 2.304, 1.575, 95% confidence interal ( CI) as 1.262-8.175, 1.324-4.818, 1.477-3.595, 1.138-2.180, P<0.05]. (3) Construction and validation of the predictive model. A nomogram predictive model for postoperative early recurrence was constructed base on the results of multivariate analysis. The C-index of predictive model was 0.786 for the training cohort and 0.734 for the validation cohort. The AUC of ROC curve of nomogram predictive model for 12-, 18-, and 24-month recurrence-free survival rate in the training cohort were 0.890 (95% CI as 0.836-0.944), 0.895 (95% CI as 0.842-0.947), and 0.887 (95% CI as 0.831-0.942), respectively. The AUC of ROC curve of nomogram predictive model for 12-, 18-, and 24-month recurrence-free survival rate in the validation cohort were 0.845 (95% CI as 0.781-0.909], 0.888 (95% CI as 0.826-0.950), and 0.919 (95% CI as 0.870-0.968), respectively. Results of calibration curve showed high consistency between the predicted results of nomogram predictive model and actual outcomes. Results of decision curve showed the nomogram predictive model with a good total net gain at a threshold of 0.10-0.50. Conclusions:Tumor burden prior to downstaging treatment, grade of ALBI score prior to SLR, AFP half-life prior to SLR, and tumor response prior to SLR are independent factors influencing early recurrence in initially unresectable HCC patients undergoing SLR following downstaging treatment. The nomogram predictive model based on these factors can effectively evaluate the prognosis of this patient population.

Objective To evaluate the efficacy,safety and economy of inclisiran in the treatment of dyslipidemia by rapid health technology assessment,and to provide evidence-based basis for clinical treatment.Methods PubMed,Web of Science,Embase,Cochrane Library,CNKI,WanFang Data,VIP,SinoMed databases,and official websites of health technology assessment(HTA)institutions were systematically searched to collect HTA reports,systematic reviews/Meta-analysis and pharmacoeconomic studies on inclisiran for the treatment of dyslipidemia from inception to December 31,2024.Two researchers independently screened the literature,extracted information and performed quality assessment of the included literature,and then qualitative synthesis and analysis of the findings were conducted.Results A total of 8 studies were included,comprising 7 systematic reviews/Meta-analysis and 1 pharmacoeconomic study.In terms of efficacy,inclisiran significantly reduced low-density lipoprotein cholesterol,apolipoprotein B,total cholesterol,triglycerides and non-high-density lipoprotein cholesterol levels in patients with dyslipidemia compared to placebo.In terms of safety,the incidence of adverse drug reactions associated with inclisiran did not differ significantly from that of placebo,with the most common adverse drug reactions being mild injection site reactions.In terms of cost-effectiveness,the current price of inclisiran made its combination therapy with statins economically unfavorable compared to statin monotherapy.Conclusion The efficacy and safety of inclisiran in the treatment of dyslipidemia are good.However,due to its current pricing,the combination therapy of inclisiran with statins is not yet cost-advantageous compared to statin monotherapy in clinical practice.

An increasing number of studies have shown that there is a close relationship between Alzheimer's disease(AD)and diabetes mellitus(DM).Traditional Chinese medicine holds that"kidney yin deficiency"is the common pathogenesis of these two diseases,while modern medicine believes that their pathogenesis involves abnormal aggregation of amyloid proteins,insulin deficiency and resistance,inflammatory response,oxidative stress,and autophagy,among others.The well-known traditional Chinese medicine formula Liuwei Dihuang Pills plays a significant role in the treatment of these two diseases with the same therapeutic approach.Therefore,this article will explore the connection between Liuwei Dihuang Pills and the treatment of AD and DM from different aspects;analyze the common etiology and pathogenesis of AD and DM,and explain the mechanism of prevention and treatment of Liuwei Dihuang Pills,with the aim of providing new ideas and methods for the integrated traditional and Western medicine prevention and treatment of AD and DM in the future.

Objective To evaluate the efficacy,safety and economy of inclisiran in the treatment of dyslipidemia by rapid health technology assessment,and to provide evidence-based basis for clinical treatment.Methods PubMed,Web of Science,Embase,Cochrane Library,CNKI,WanFang Data,VIP,SinoMed databases,and official websites of health technology assessment(HTA)institutions were systematically searched to collect HTA reports,systematic reviews/Meta-analysis and pharmacoeconomic studies on inclisiran for the treatment of dyslipidemia from inception to December 31,2024.Two researchers independently screened the literature,extracted information and performed quality assessment of the included literature,and then qualitative synthesis and analysis of the findings were conducted.Results A total of 8 studies were included,comprising 7 systematic reviews/Meta-analysis and 1 pharmacoeconomic study.In terms of efficacy,inclisiran significantly reduced low-density lipoprotein cholesterol,apolipoprotein B,total cholesterol,triglycerides and non-high-density lipoprotein cholesterol levels in patients with dyslipidemia compared to placebo.In terms of safety,the incidence of adverse drug reactions associated with inclisiran did not differ significantly from that of placebo,with the most common adverse drug reactions being mild injection site reactions.In terms of cost-effectiveness,the current price of inclisiran made its combination therapy with statins economically unfavorable compared to statin monotherapy.Conclusion The efficacy and safety of inclisiran in the treatment of dyslipidemia are good.However,due to its current pricing,the combination therapy of inclisiran with statins is not yet cost-advantageous compared to statin monotherapy in clinical practice.

Objective To examine the serological and molecular prevalence as well as genotype characteristics of human Parvovirus B19 blood donors in Lanzhou,and to provide evidence for developing a screening strategy to reduce the risk of blood transfusion transmission.Methods A total of 5 722 blood samples collected from Lanzhou blood donors from April 2023 to October 2023 were tested for B19 DNA using real-time quantitative PCR(qRT-PCR).Additionally,383 samples were screened for anti-B19 IgG and anti-B19 IgM using synchronous enzyme-linked immunoassay(ELISA).Viral load and VP1 sequencing were conducted on the B19 DNA-positive samples and the Neighbor-Joining(N-J)method was used to construct an evolutionary tree for the sequenced samples.Results The prevalence of human Parvovirus B19 DNA,IgG antibody and IgM antibody was 0.47%(27/5 722),25.59%(98/383)and 0.26%(1/383),respectively,and the samples positive for B19 DNA,IgG antibody and IgM antibody were 0.26%(1/383).The co-positivity rate for B19 DNA and IgG antibody was 6.27%(24/383),while the positivity rates for B19 DNA or IgG antibody alone were 0.52%(2/383)and 19.06%(73/383),respectively.Viral loads ranged from 4.24 IU/ml to 5.67×102 IU/ml,all below 104 IU/ml.There was no statistical significance in the positive rate of B19 DNA in gender(χ2=0.86,P=0.35),but there was statistical significance in the positive rate of B19 DNA among all age groups(χ2=8.00,P=0.02).The highest positive rate of B19 DNA was 0.65%in the 18～30 age group.There was statistical significance in the positive rate of B19 IgG antibody in gender(χ2=5.03,P=0.02),but there was no statistical significance in the positive rate of B19 IgG antibody among all age groups(χ2=0.51,P=0.77).The highest positive rate of B19 IgG antibody was 29.09%in the age group of 41 to 60.There was no significant difference in the positive rate of B19 IgM antibody in gender(χ2=2.84,P=0.09).The highest positive rate of B19 IgM was 3.85%in the age group of 18～30 years old.Based on the VP1 sequence,the phylogenetic tree revealed that B19 strains in Lanzhou formed a distinct cladistic lineage within genotype 1,predominantly represented by genotype 1b.Conclusion The prevalence of B19 DNA and IgM antibodies among blood donors in the Lanzhou area is low,and so is the viral load.Therefore the risk of transmitting B19 through blood transfusion is relatively small.Since the prevalence of B19 IgG antibody is high,it is suggested to closely monitor the transmission situation in the area,regularly monitor the prevalence of B19 among blood donors,and track the situation of B19 DNA-positive blood donors to recipients to ensure the safety of clinical blood transfusion.

Objective:To investigate the factors influencing early recurrence for patients with initially unresectable hepatocellular carcinoma (HCC) who underwent salvage liver resection (SLR) following transcatheter arterial chemoembolization-based downstaging treatment, and construct a predictive model to evaluate its predicting performance.Methods:The retrospective cohort study was constructed. The clinicopathological data of 305 patients with initially unresectable HCC who were admitted to 4 medical centers in China, including the Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital) et al, from January 2019 to December 2021 were collected. There were 286 males and 19 females, aged (48.7±10.4)years. A total of 133 patients who were admitted from January 2019 to December 2020 were set as the training cohort, and the other 172 patients who were admitted from January to December 2021 were set as the validation cohort. Observation indicators: (1) postoperative recurrence-free survival in HCC patients; (2) analysis of factors influencing postoperative early recurrence in HCC patients; (3) construction and validation of the predictive model. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the rank sum test. Univariate and multivariate analyses were conducted using the Cox regre-ssion model. The Kaplan-Meier method was used to calculate survival. The Log-rank test was used for survival analysis. The predicting performance of the model was evaluated using the concordance index (C-index) and the area under curve (AUC) of time-dependent receiver operating characteristic (ROC) curve, and the accuracy of the model was validated using the calibration curve. The total net gain of the model was evaluated using the decision curve. Results:(1) Postoperative recurrence-free survival in HCC patients. The recurrence-free survival time of 133 HCC patients in the training cohort was 10.0(range, 1.5-24.0)months, with 1-, 2-year recurrence-free survival rate of 47.3% and 36.8%. The recurrence-free survival time of 172 HCC patients in the validation cohort was 11.0(range, 1.0-24.0)months, with 1-, 2-year recurrence-free survival rate of 51.7% and 37.2%. There was no significant difference in recurrence-free survival between patients in the training cohort and the validation cohort ( χ2=0.075, P>0.05). (2) Analysis of factors influencing postoperative early recur-rence in HCC patients. Results of multivariate analysis showed that tumor burden prior to down-staging treatment, grade of albumin-bilirubin (ALBI) score prior to SLR, alpha-fetoprotein (AFP) half-life prior to SLR, and tumor response prior to SLR were independent factors influencing early recurrence in HCC patients after surgery [ hazard ratio=3.212, 2.526, 2.304, 1.575, 95% confidence interal ( CI) as 1.262-8.175, 1.324-4.818, 1.477-3.595, 1.138-2.180, P<0.05]. (3) Construction and validation of the predictive model. A nomogram predictive model for postoperative early recurrence was constructed base on the results of multivariate analysis. The C-index of predictive model was 0.786 for the training cohort and 0.734 for the validation cohort. The AUC of ROC curve of nomogram predictive model for 12-, 18-, and 24-month recurrence-free survival rate in the training cohort were 0.890 (95% CI as 0.836-0.944), 0.895 (95% CI as 0.842-0.947), and 0.887 (95% CI as 0.831-0.942), respectively. The AUC of ROC curve of nomogram predictive model for 12-, 18-, and 24-month recurrence-free survival rate in the validation cohort were 0.845 (95% CI as 0.781-0.909], 0.888 (95% CI as 0.826-0.950), and 0.919 (95% CI as 0.870-0.968), respectively. Results of calibration curve showed high consistency between the predicted results of nomogram predictive model and actual outcomes. Results of decision curve showed the nomogram predictive model with a good total net gain at a threshold of 0.10-0.50. Conclusions:Tumor burden prior to downstaging treatment, grade of ALBI score prior to SLR, AFP half-life prior to SLR, and tumor response prior to SLR are independent factors influencing early recurrence in initially unresectable HCC patients undergoing SLR following downstaging treatment. The nomogram predictive model based on these factors can effectively evaluate the prognosis of this patient population.