Tuberculosis is a zoonotic disease posing a substantial public health threat.Immunological diagnosis and vaccine im-munization are both necessary to control tuberculosis prevalence.However,the identical antigenic components in diagnostic reagents and vaccines hinder the use of animal vaccines and limit the specificity of clinical diagnosis in humans.Differentiating infected from vaccinated animals can overcome these problems.This article reviews the progress in differential diagnosis research from three as-pects:the diagnostic effects of antigens,methods for discovering new antigens,and screening of new host immune markers,to provide a theoretical basis for future research.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Tuberculosis is a zoonotic disease posing a substantial public health threat.Immunological diagnosis and vaccine im-munization are both necessary to control tuberculosis prevalence.However,the identical antigenic components in diagnostic reagents and vaccines hinder the use of animal vaccines and limit the specificity of clinical diagnosis in humans.Differentiating infected from vaccinated animals can overcome these problems.This article reviews the progress in differential diagnosis research from three as-pects:the diagnostic effects of antigens,methods for discovering new antigens,and screening of new host immune markers,to provide a theoretical basis for future research.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Objective To comprehensively analyze the clinical characteristics and risk factors of children with refractory mycoplasma pneumonia(RMPP),precisely identify the joint predictors in these children,and construct a prediction model.This aims to offer a scientific foundation for the early identification of RMPP and the formulation of accurate treatment and medication strategies.Methods A retrospective analysis was performed on the clinical data of 282 children diagnosed with mycoplasma pneumoniae pneumonia(MPP)who were admitted to the Pediatric Department of the Seventh Medical Center of the Chinese People's Liberation Army General Hospital between August 1,2023,and February 29,2024.Among these children,119 with RMPP were classified into the RMPP group,while the remaining 163 with general MPP(GMPP)were assigned to the GMPP group.The clinical data of both groups,encompassing age,gender,duration of fever,symptoms,laboratory test indices,chest imaging data,complications,etc.,were compared.A logistic probability model(LogP model)for joint application was constructed.The discriminatory ability of the model was evaluated using the area under the receiver operating characteristic(ROC)curve,and the calibration of the model was assessed by means of a calibration curve.Results In comparison with the GMPP group,children in the RMPP group exhibited a significantly longer duration of fever(P=0.002).Moreover,they had a higher incidence of complications,including myocardial damage and coagulation dysfunction(P<0.05).Regarding inflammatory markers,the levels of C-reactive protein(CRP),procalcitonin(PCT),and lactate dehydrogenase(LDH)were notably elevated in the RMPP group(P<0.05),whereas the level of albumin(Alb)was lower(P=0.001).In the RMPP group,the levels of interleukin-2(IL-2),interleukin-5(IL-5),interleukin-8(IL-8),interleukin-1β(IL-1β),and D-Dimer were increased,while the levels of interleukin-6(IL-6)and interleukin-17(IL-17)were decreased(P<0.05).Chest computed tomography(CT)scans revealed a higher proportion of lung consolidation,pleural effusion,and atelectasis in the RMPP group(P<0.05).Multivariate logistic regression analysis demonstrated that CRP,total bilirubin(T-BIL),LDH,IL-17,and prothrombin time(PT)were independent risk factors for RMPP(P<0.05).The receiver operating characteristic(ROC)predictive model established based on these factors had an area under the curve(AUC)of 0.787(95%confidence interval[CI]:0.693～0.880),with a cutoff value of 0.421,a sensitivity of 0.786,and a specificity of 0.660.The calibration curve indicated that the predicted probability matched well with the reference probability,and there was no statistical difference in the results of the Hosmer-Lemeshow test(P>0.05).Conclusions The clinical features of children with RMPP are predominantly characterized by prolonged fever,moderate lung lesions,other organ injuries,and high inflammatory markers.CRP,T-BIL,LDH,IL-17,and PT can act as independent risk factors for RMPP.

Objective:To explore the application and clinical significance of pathological diagnostic criteria for medically refractory epilepsy in children.Methods:Cross-sectional study.A retrospective analysis was conducted on 490 children(pathology involved) with medically refractory epilepsy treated continuously in the Pediatric Epilepsy Center of Peking University First Hospital from January 2019 to May 2022.The distribution of different pathological types was observed, and the differences in clinical characteristics among different pathological types were analyzed through Kruskal-Wallis or χ2 tests.The impact of clinical and pathological features on patient prognosis was evaluated through regression analysis. Results:Focal cortical dysplasia (FCD) was the predominant lesion (49.59%, 243/490).The electroencephalograms ( χ2=6.720, P=0.035) and clinical seizure characteristics ( χ2=26.370, P<0.001) in FCDⅡ were more focal than those in FCD Ⅰ and Ⅲ.Moreover, the proportions of focal resection in surgery ( χ2=24.286, P<0.001) and central involvement ( χ2=22.849, P<0.001) in FCDⅡ were higher than those in FCD Ⅰ and Ⅲ.Univariate and multivariate regression analyses revealed that FCD Ⅱ had a better prognosis than other dysplastic patients among the 375 cases of dysplasia ( P=0.049).Next-generation sequencing was performed on 35 cases of cortical malformations with such morphological characteristics as increased numbers of neurons in the white matter and Olig2-positive glial cell hyperplasia, and SLC35A2 mutations were detected in 2 cases (5.71%). Conclusions:Pathology of refractory epilepsy is specialized and continuously evolving.Standardized specimen processing and the accumulation of morphological, immunohistochemical, and molecular genetic data provide the foundation for clarifying the neuropathological nature of epilepsy, improving integrated classification, and advancing prognosis prediction and targeted therapy.

Objective:To explore the application and clinical significance of pathological diagnostic criteria for medically refractory epilepsy in children.Methods:Cross-sectional study.A retrospective analysis was conducted on 490 children(pathology involved) with medically refractory epilepsy treated continuously in the Pediatric Epilepsy Center of Peking University First Hospital from January 2019 to May 2022.The distribution of different pathological types was observed, and the differences in clinical characteristics among different pathological types were analyzed through Kruskal-Wallis or χ2 tests.The impact of clinical and pathological features on patient prognosis was evaluated through regression analysis. Results:Focal cortical dysplasia (FCD) was the predominant lesion (49.59%, 243/490).The electroencephalograms ( χ2=6.720, P=0.035) and clinical seizure characteristics ( χ2=26.370, P<0.001) in FCDⅡ were more focal than those in FCD Ⅰ and Ⅲ.Moreover, the proportions of focal resection in surgery ( χ2=24.286, P<0.001) and central involvement ( χ2=22.849, P<0.001) in FCDⅡ were higher than those in FCD Ⅰ and Ⅲ.Univariate and multivariate regression analyses revealed that FCD Ⅱ had a better prognosis than other dysplastic patients among the 375 cases of dysplasia ( P=0.049).Next-generation sequencing was performed on 35 cases of cortical malformations with such morphological characteristics as increased numbers of neurons in the white matter and Olig2-positive glial cell hyperplasia, and SLC35A2 mutations were detected in 2 cases (5.71%). Conclusions:Pathology of refractory epilepsy is specialized and continuously evolving.Standardized specimen processing and the accumulation of morphological, immunohistochemical, and molecular genetic data provide the foundation for clarifying the neuropathological nature of epilepsy, improving integrated classification, and advancing prognosis prediction and targeted therapy.

Objective: To explore the brain-predicted age difference (Brain-PAD) in patients with type 2 diabetes mellitus (T2DM) by a machine learning prediction model based on structural magnetic resonance ( sMRI) in the Southwest University Adult Lifespan Dataset (SALD) , and to reveal the relationship between Brain-PAD and dura- tion of T2DM and cognition . Methods: Group comparisons about demographic variables and cognitive function were conducted respectively in local database of 104 T2DM patients and 83 healthy controls (HC) . The prediction model via Gaussian process regression (GPR) was constructed by training sMRI data of 329 healthy volunteers in SALD , then its performance was validated and evaluated . Furthermore , Brain-PAD ( predicted age-chronological age) in the local database was calculated . Group comparisons of Brain-PAD between T2DM patients and HCs were conducted by Mann-Whitney U test. Finally , Pearson correlation coefficient (r) was calculated between Brain-PAD and duration of disease and cognition . Results: Poor performance in auditory verbal learning test (AVLT)-delayed recall , AVLT-recognition , symbol digital modalities test (SDMT) (P < 0. 05) , and increased Brain-PAD were ob- served in T2DM patients , compared with HCs [1 . 619 ( - 4. 001 , 8. 272) years vs - 1 . 289 ( - 4. 128 , 4. 134) years , Z = 2. 056 , P = 0. 034] . Notably , the median of Brain-PAD in T2DM group was positive , indicating that the brain of T2DM patient maybe relatively “older”than his chronological age . Brain-PAD in T2DM group was as- sociated with performance in AVLT-immediate recall ( r = 0. 291 , P = 0. 003) , AVLT-delayed recall ( r = 0. 248 , P = 0. 011) , SDMT( r = 0. 376 , P = 0. 001) and trail making test (TMT)-A ( r = - 0. 206 , P = 0. 036) . However , the relationships between Brain-PAD and duration of T2DM were not explored . Conclusion Decreased cognitive function in patients with T2DM is demonstrated in this study . The machine learning prediction model based on sMRI supports the identification of brain aging objectively in patients with T2DM .