Objective To explore the biological functions of pyroptosis-related genes in pneumonic plague using bioinformatics methods,and to evaluate their potential applicability as diagnostic markers.Methods The pneumonic plague-related dataset GSE220123 was retrieved from the Gene Expression Omnibus(GEO)database and screened for differentially expressed pyroptosis-related genes(DE-PRGs).The functions of DE-PRGs were studied via Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,and immune infiltration analysis.The hub genes were identified via protein-protein interaction(PPI)network analysis,and further screened for key genes with sustained high expression characteristics based on differential expression analysis.The relative expression levels of the key genes were verified using the reverse transcription real-time quantitative PCR(qPCR)method.Results A total of 17 DE-PRGs were screened,and PPI network analysis revealed 7 Hub genes.Among them,Casp4 continued to be up-regulated during the course of pneumonic plague.The results of reverse transcription qPCR were consistent with the those of bioinformatic analyses.Conclusion DE-PRGs play a crucial role in the immune response of pneumonic plague,especially Casp4,which has significant applications as a diagnostic biomarker and potential therapeutic target for pneumonic plague.

Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.

Aim To study the renal protective effect of balanophora polysaccharide(BPS)on diabetic nephrop-athy(DN)mice and explore the related mechanisms.Methods A DN mouse model was induced using a high-fat diet combined with intraperitoneal injection of streptozotocin(STZ),which was indicated by fasting blood glucose higher than 11.1 mmol·L-1,accompa-nied by diabetic symptoms such as polydipsia,polydia-gia,polyuria and weight loss,then BPS intervention was performed.Body weight and fasting blood glucose of each group mice were detected;automatic biochemical analyzer was used to detect blood creatinine(SCr),blood urea nitrogen(BUN),24 h urinary protein(24 h UP),triglycerides(TG),total cholesterol(TC),alanine aminotransferase(ALT)content;ELISA was applied to determine serum inflammatory factor interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)level;HE and Masson staining were employed to observe renal his-topathological morphology;Western blot was used to de-tect Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),nuclear factor κB(NF-κB)for pro-tein expression.Results Compared with the model group,after BPS,body weight and fasting blood glucose decreased(P＜0.01 or P＜0.05);SCr,BUN,24 h UP,TC,TG and ALT significantly decreased(P＜0.01 or P＜0.05);the levels of the proinflammatory factors TNF-α and IL-6 were significantly reduced(P＜0.01 or P＜0.05);renal tissue injury and fibrosis decreased;TLR4,MyD88,NF-κB protein expression significantly decreased(P＜0.01 or P＜0.05).Conclusion BPS has a protective effect on the kidneys of DN mice,re-ducing the blood glucose level,improving liver and kid-ney function,alleviating renal tissue damage and renal fibrosis,and reducing inflammation response.Its mecha-nism may be related to the regulation of TLR4/MyD88/NF-κB signaling pathway.

Objective:To explore the correlation between serum ferritin(SF)levels and the efficacy of platelet transfusion in patients with malignant hematological diseases.Methods:Patients with malignant hematological diseases who received repeated transfusions of apheresis platelets in Department of Hematology of Aerospace Center Hospital in 2023 were selected.The platelet corrected count increment(CCI)was used to evaluate the efficacy of platelet transfusion.The correlations between sex,age,disease type,transplantation history,red blood cell transfusion history,and SF level and the efficacy of platelet transfusion were analyzed.Results:A total of 87 patients were included,with a cumulative 326 person-times platelet transfusions.As suggested by one-way analysis of variance,compared with the patients in the age groups of 24-45 years old and 46-66 years old,the patients in the age group of 2-23 years old had a better efficacy of platelet transfusion(P=0.004,P=0.004).There was no significant difference in the efficacy of platelet transfusion between the patients in the age group of 24-45 years old and those in the age group of 46-66 years old(P=0.876).Compared with the patients who had a history of red blood cell transfusion within 3 days,the patients without a history of red blood cell transfusion within 3 days had a better efficacy of platelet transfusion(P＜0.001).Compared with the groups with SF levels of 1.44-2.78 ng/L and＞2.78 ng/L,the group with SF levels＜1.44 ng/L had a better efficacy of platelet transfusion(P=0.028,P＜0.001).Compared with the group with SF levels＞2.78 ng/L,the group with SF levels of 1.44-2.78 ng/L had a better efficacy of platelet transfusion(P=0.001).After adjusting for age and the history of red blood cell transfusion,the transfusion efficacy of the group with SF levels＜1.44 ng/L was better than that of the groups with SF levels of 1.44-2.78 ng/L and＞2.78 ng/L(P=0.021,P＜0.001);Compared with the group with SF levels＞2.78 ng/L,the group with SF levels of 1.44-2.78 ng/L had a better efficacy of platelet transfusion(P=0.001).Both univariate and multivariate linear regression models showed that SF levels were negatively correlated with the efficacy of platelet transfusion(P＜0.001).Conclusion:There is a negative correlation between SF levels and the efficacy of platelet transfusion in patients with malignant hematological diseases.Detection of SF levels may provide guidance for predicting the efficacy of platelet transfusion.

Objective To observe brain function changes in insomnia disorder(ID)patients and therapeutic effect of repeated transcranial magnetic stimulation(rTMS)based on resting-state functional MRI(rs-fMRI).Methods Totally 37 patients with ID(ID group)and 20 healthy subjects(control group)were prospectively enrolled.The scores of sleep condition and psychological state scales were compared between groups,also within ID group before and after rTMS treatment.Brain regions with amplitude of low frequency fluctuations(ALFF)and regional homogeneity(ReHo)being significantly different between groups were evaluated based on brain rs-fMRI,and voxel-based resting-state functional connectivity(FC)analysis was performed in the above regions and the predefined regions of interest.Results Before treatment,Pittsburgh sleep quality index(PSQI),insomnia severity index(ISI),Epworth sleepiness score(ESS),Beck depression inventory(BDI)score and Beck anxiety inventory(BAI)score in ID group were all higher than those in control group(all P＜0.05).ALFF values and ReHo of the right median cingulate and paracingulate gyrus(Cingulum_Mid_R)were lower in ID group than those in control group(all FWE correctedP＜0.05).FC between Cingulum_Mid_R and the left anterior cingulate gyrus and cingulate gyrus(Cingulum_Ant_L)decreased,so did that between the left hippocampus(Hippocampus_L)and the right frontal gyrus(Frontal_Mid_R)(all FWE corrected P＜0.05).After rTMS,PSQI,ISI and ESS scores of ID patients decreased compared to those before treatment(all P＜0.05),but no significant change of the above neuroimaging indicators was detected(all FWE corrected P＞0.05).Conclusion ID caused synchronous decrease of Cingulum_Mid_R ALFF value and ReHo,as well as weakened FC between frontal cingulate gyrus and frontal with lobe limbic system.rTMS could improve sleep and mental state of ID patients,but its impact on neuroimaging needed further investigation.

Objective To explore the application value of anhydrous ethanol as an alternative to methanol in the preparation of chromosomal specimens from peripheral blood lymphocytes, and to establish a set of quantitative analytical methods for objectively evaluating the effectiveness of specimen preparation. Methods Residual blood samples from routine laboratory slide preparation were used for lymphocyte culture. The standard slide preparation method was employed. The fixative in the control group was methanol and glacial acetic acid (3∶1). Four experimental groups were set up based on the ratio of anhydrous ethanol to glacial acetic acid in the fixative (volume ratios of 3∶1, 5∶1, 7∶1, and 9∶1 for experimental groups 1, 2, 3, and 4, respectively). A chromosomal analysis was conducted using an automated chromosome scanning/image analysis system to evaluate the morphology and dispersion of metaphase chromosomes in both control and experimental groups. Comparisons were made between the control and experimental groups regarding the dic + r aberration rate, ace aberration rate, chromosomal aberration rate, chromosome dispersion index, chromosome overlapping ratio, and dispersion index/overlapping ratio. Results Microscopic evaluation revealed that the preparation quality of experimental groups 1 and 2 was comparable to the control group. No statistically significant differences were observed in dic + r aberration rate between each of the experimental groups and the control (P > 0.05). All experimental groups except group 4 showed no significant differences in ace aberration rate and chromosome aberration rate compared with the control group (P > 0.05). Experimental groups 1 and 2 showed no significant differences in chromosome dispersion index, overlapping ratio, and dispersion index/overlapping ratio compared with the control group (P > 0.05). Conclusion A mixture of anhydrous ethanol and glacial acetic acid at a 5∶1 ratio is recommended for use as a fixative in the preparation of chromosomal specimens from peripheral blood lymphocytes. A quantitative index system for assessing the quality of chromosomal specimens was established, enabling objective evaluation of slide preparation effectiveness.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

To achieve rapid and visual detection of Plasmodium vivax,a detection method based on recombinase polymerase amplification(RPA)technology and lateral flow dipstick(LFD)was established and evaluated.Targeting the conserved sequence of the P.vivax 18S rRNA gene(GenBank:DQ660817.1)as the target sequence,primers and probes were designed with Primer Premier 5,and the P.vivax recombinant plasmid(pUCPv)was constructed as the standard.A sensitive and specific RPA-LFD-based rapid visual detection method for P.vivax nucleic acids was established.The plasmid standard was serially diluted 10-fold to concentrations of 1×103,1×102,1×101,1×10?,and 1×10?1 copies/μL for sensitivity testing.To evaluate specificity,whole blood DNA samples from patients infected with Plasmodium falciparum,Plasmodium malariae,Plasmodium ovale,or Leishmania donovani,as well as healthy participants,were tested by RPA-LFD.Additionally,The assay′s accuracy was evaluated by testing whole blood DNA samples from 24 confirmed P.vivax-infected patients.This study successfully established a sensitive,specific,and rapid visual RPA-LFD method for detecting P.vivax nucleic acids.The assay can complete P.vivax detection within 20 minutes under isothermal conditions at 39 ℃,achieving a sensitivity of 1 copy/μL.There is no significant cross reaction with parasites such as other Plasmodium species and L.donovani,and the specificity is 100%.All 24 DNA samples from confirmed P.vivax patients were detected,showing a 100%detection rate.The developed RPA-LFD assay exhibits excellent sensitivity and specificity,requires only simple heating equipment,and is user-friendly.This rapid visual detection method is particularly suitable for P.vivax screening in low-resource settings.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

Aim To study the renal protective effect of balanophora polysaccharide(BPS)on diabetic nephrop-athy(DN)mice and explore the related mechanisms.Methods A DN mouse model was induced using a high-fat diet combined with intraperitoneal injection of streptozotocin(STZ),which was indicated by fasting blood glucose higher than 11.1 mmol·L-1,accompa-nied by diabetic symptoms such as polydipsia,polydia-gia,polyuria and weight loss,then BPS intervention was performed.Body weight and fasting blood glucose of each group mice were detected;automatic biochemical analyzer was used to detect blood creatinine(SCr),blood urea nitrogen(BUN),24 h urinary protein(24 h UP),triglycerides(TG),total cholesterol(TC),alanine aminotransferase(ALT)content;ELISA was applied to determine serum inflammatory factor interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)level;HE and Masson staining were employed to observe renal his-topathological morphology;Western blot was used to de-tect Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),nuclear factor κB(NF-κB)for pro-tein expression.Results Compared with the model group,after BPS,body weight and fasting blood glucose decreased(P＜0.01 or P＜0.05);SCr,BUN,24 h UP,TC,TG and ALT significantly decreased(P＜0.01 or P＜0.05);the levels of the proinflammatory factors TNF-α and IL-6 were significantly reduced(P＜0.01 or P＜0.05);renal tissue injury and fibrosis decreased;TLR4,MyD88,NF-κB protein expression significantly decreased(P＜0.01 or P＜0.05).Conclusion BPS has a protective effect on the kidneys of DN mice,re-ducing the blood glucose level,improving liver and kid-ney function,alleviating renal tissue damage and renal fibrosis,and reducing inflammation response.Its mecha-nism may be related to the regulation of TLR4/MyD88/NF-κB signaling pathway.