Objective To explore the ^“contribution^” of different exposures to cardiovascular diseases at the population level and to construct a risk prediction model for the effective allocation of prevention resources. Methods The CHNS (China Health and Nutrition Survey) database was used. In 2009, 2011 and 2015, 9 899 permanent residents aged 35 to 75 years in 10 provinces and cities in the central and eastern regions (Beijing, Liaoning, Heilongjiang, Shanghai, Shandong, Henan, Hubei, Hunan, Guangxi and Jiangsu) were selected as the research subjects. A single-factor analysis was conducted to examine the risk factors including sex, age, BMI, marital status, urban/rural area, sleep time, smoking, alcohol consumption, diabetes, education, and health insurance. The multifactor-adjusted population-attributable risk of certain risk factors was also estimated based on logistic regression analysis. The cardiovascular disease (CVD) risk prediction model was developed using a modeling group of 6 927 randomly selected individuals (70%) and a validation group of 2 974 individuals (30%). The model's differentiation and calibration were assessed using the receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow goodness-of-fit test. Results The results showed that the adjusted population attributable risk and 95% confidence interval for BMI, sleep time, smoking, drinking and diabetes were 32.20% (27.67%-36.89%), 7.90% (1.68%-16.58%), 18.56% (11.35%-26.24%), 6.47% (0.11%-13.25%) and 5.73% (4.42%-7.03%). The results of multivariate adjusted population attributable risk percentage showed that BMI was the dominant cause of cardiovascular diseases, followed by smoking, sleep time, drinking and diabetes. The low-risk prevalence rate was 18.44%, the higher-risk prevalence rate was 14.19%, and the high-risk prevalence rate was 42.52%. The area under ROC curve AUC was 0.711, P<0.001, and Hosmer-Lemeshow goodness of fit test showed P=0.257. Conclusion In the future, it is important to focus on high-risk groups , control body mass index to the normal range, and reduce smoking , which is of great significance for the prevention of cardiovascular diseases. The risk prediction model has the value of good differentiation and practicability , and can provide certain prediction ability for the prevention of cardiovascular diseases.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

OBJECTIVE The non-volatile and volatile chemical components in Yin-Qiao-Qing-Re Tablets were analyzed sepa-rately using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS)and Gas Chromatography Mass Spectrometry(GC-MS).METHODS The non-volatile components were analyzed using a Waters ACQUITY UPLC BEH C18 column(2.1 mm×100 mm,1.7 μm),with a mobile phase consisting of 0.1％formic acid aqueous solution(A)and acetonitrile(B)for gradient elution,a flow rate of 0.35 mL·min-1,an injection volume of 5 μL,and a column temperature of 30 ℃;the volatile components were analyzed using an Agilent SH-I-5MS column(5％Phenyl Methyl Silox,30 m×250 μm,0.25 μm);the procedure was temperature-programmed,with an injection volume of 1 μL,a split ratio of 10∶1,a flow rate of 1.0 mL·min-1,and an inlet temperature of 200 ℃.RESULTS A total of 134 non-volatile chemical components and 23 volatile components were analyzed and identified from Yin-Qiao-Qing-Re Tablets,among which 49 compounds were confirmed through comparison with reference stand-ards.The non-volatile components mainly include 27 flavonoids,21 organic acids,15 lignans,14 iridoids,12 phenylethanoid glyco-sides,11 saponins,10 alkaloids,5 terpenes,4 amino acids,3 phenylpropanoids,3 nucleosides,3 xanthones,3 phenolic glycosides,2 chromones and 1 carbohydrate.The volatile components mainly include 11 monoterpenes,5 alcohols and phenols,3 alkenes,2 ke-tones,1 ester,and 1 hydrocarbon.CONCLUSION This study rapidly identifies the chemical components of Yin-Qiao-Qing-Re Tablets,laying a preliminary foundation for research on the pharmacodynamic substances of Yin-Qiao-Qing-Re Tablets and the im-provement of quality control standards.

OBJECTIVE The non-volatile and volatile chemical components in Yin-Qiao-Qing-Re Tablets were analyzed sepa-rately using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS)and Gas Chromatography Mass Spectrometry(GC-MS).METHODS The non-volatile components were analyzed using a Waters ACQUITY UPLC BEH C18 column(2.1 mm×100 mm,1.7 μm),with a mobile phase consisting of 0.1％formic acid aqueous solution(A)and acetonitrile(B)for gradient elution,a flow rate of 0.35 mL·min-1,an injection volume of 5 μL,and a column temperature of 30 ℃;the volatile components were analyzed using an Agilent SH-I-5MS column(5％Phenyl Methyl Silox,30 m×250 μm,0.25 μm);the procedure was temperature-programmed,with an injection volume of 1 μL,a split ratio of 10∶1,a flow rate of 1.0 mL·min-1,and an inlet temperature of 200 ℃.RESULTS A total of 134 non-volatile chemical components and 23 volatile components were analyzed and identified from Yin-Qiao-Qing-Re Tablets,among which 49 compounds were confirmed through comparison with reference stand-ards.The non-volatile components mainly include 27 flavonoids,21 organic acids,15 lignans,14 iridoids,12 phenylethanoid glyco-sides,11 saponins,10 alkaloids,5 terpenes,4 amino acids,3 phenylpropanoids,3 nucleosides,3 xanthones,3 phenolic glycosides,2 chromones and 1 carbohydrate.The volatile components mainly include 11 monoterpenes,5 alcohols and phenols,3 alkenes,2 ke-tones,1 ester,and 1 hydrocarbon.CONCLUSION This study rapidly identifies the chemical components of Yin-Qiao-Qing-Re Tablets,laying a preliminary foundation for research on the pharmacodynamic substances of Yin-Qiao-Qing-Re Tablets and the im-provement of quality control standards.

Objective:To explore the values of reticulin fiber staining (RFS) in evaluating bone marrow (BM) involvement of lymphoma and in grading of BM biopsy from adult lymphoma patients.Methods:Retrospectively,354 cases of adult lymphoma were collected from November 2023 to May 2024 at Peking University Cancer Hospital. BM samples were stained with RFS and immunohistochemical staining (IHC), and flow cytometry (FCM) was also performed with the BM aspirations simultaneously. RFS was graded according to the European Consensus, as high grade (grade 2-3) indicating BM involvement in the study. BM involvement was considered as definite if no less than two positive findings among IHC, FCM, and RFS. Statistical analyses were performed via SPSS software (V23.0).Results:In this series, 52.3% (185/354) of the patients were male; 35.0% (124/354) aged >60 years; BM involvements were found in 34.5% (122/354) cases with high grade of RFS, which, in turn, were lymphoblastic leukemia/lymphoma (ALL/LBL) group (4/4), indolent B-cell lymphoma (IndBCL) group (49.1%, 53/108), transformed B-cell lymphoma (TrBCL) group (2/5), invasive B-cell lymphoma (InvBCL) group (26.5%, 41/155), T and NK cell lymphoma (TNKCL) group (27.3%, 12/44) and classical Hodgkin lymphoma (CHL) group (26.3%, 10/38); if classified by specific types, T-ALL/LBL (2/2), B-ALL/LBL (2/2) and CLL/SLL (8/10) ranked top three. In terms of the positive rate of BM involvement evaluated by RFS, no significant difference was seen between either gender or age groups ( χ2=3.416, P=0.332 and χ2=4.200, P=0.241); however, significant differences were observed between different lymphoma groups and types ( χ2=29.961, P=0.012 and χ2=102.546, P<0.001, respectively). BM invasion rates indicated by IHC and FCM were 25.4% (90/354) and 13.8% (49/354), respectively. The overall BM invasion rate was 24.3% (86/354), and the sensitivity of RFS, IHC, and FCM was 90.8%, 97.8%, and 55.8%, and specificity was 84.1%, 99.6%, and 98.9%, respectively. Overall, the concordance rate of RFS with IHC and FCM was 83.6% and 74.0%, respectively, including 85.8% and 74.2% for InvBCL group, 79.6% and 75.0% for IndBCL group, 84.1% and 75.0% for TNKCL group, 81.6% and 73.7% for CHL group, 5/5 and 2/5 for TrBCL group, and 4/4 and 3/4 for ALL/LBL group. Conclusions:In the evaluation of BM involvement status of adult lymphoma, high sensitivity and specificity are observed by RFS, and high concordance is also noted with both IHC and FCM. Thus, the BM infiltrating status of adult lymphoma could be evaluated more accurately by a combined usage of the three methods.

Objective:To explore the values of reticulin fiber staining (RFS) in evaluating bone marrow (BM) involvement of lymphoma and in grading of BM biopsy from adult lymphoma patients.Methods:Retrospectively,354 cases of adult lymphoma were collected from November 2023 to May 2024 at Peking University Cancer Hospital. BM samples were stained with RFS and immunohistochemical staining (IHC), and flow cytometry (FCM) was also performed with the BM aspirations simultaneously. RFS was graded according to the European Consensus, as high grade (grade 2-3) indicating BM involvement in the study. BM involvement was considered as definite if no less than two positive findings among IHC, FCM, and RFS. Statistical analyses were performed via SPSS software (V23.0).Results:In this series, 52.3% (185/354) of the patients were male; 35.0% (124/354) aged >60 years; BM involvements were found in 34.5% (122/354) cases with high grade of RFS, which, in turn, were lymphoblastic leukemia/lymphoma (ALL/LBL) group (4/4), indolent B-cell lymphoma (IndBCL) group (49.1%, 53/108), transformed B-cell lymphoma (TrBCL) group (2/5), invasive B-cell lymphoma (InvBCL) group (26.5%, 41/155), T and NK cell lymphoma (TNKCL) group (27.3%, 12/44) and classical Hodgkin lymphoma (CHL) group (26.3%, 10/38); if classified by specific types, T-ALL/LBL (2/2), B-ALL/LBL (2/2) and CLL/SLL (8/10) ranked top three. In terms of the positive rate of BM involvement evaluated by RFS, no significant difference was seen between either gender or age groups ( χ2=3.416, P=0.332 and χ2=4.200, P=0.241); however, significant differences were observed between different lymphoma groups and types ( χ2=29.961, P=0.012 and χ2=102.546, P<0.001, respectively). BM invasion rates indicated by IHC and FCM were 25.4% (90/354) and 13.8% (49/354), respectively. The overall BM invasion rate was 24.3% (86/354), and the sensitivity of RFS, IHC, and FCM was 90.8%, 97.8%, and 55.8%, and specificity was 84.1%, 99.6%, and 98.9%, respectively. Overall, the concordance rate of RFS with IHC and FCM was 83.6% and 74.0%, respectively, including 85.8% and 74.2% for InvBCL group, 79.6% and 75.0% for IndBCL group, 84.1% and 75.0% for TNKCL group, 81.6% and 73.7% for CHL group, 5/5 and 2/5 for TrBCL group, and 4/4 and 3/4 for ALL/LBL group. Conclusions:In the evaluation of BM involvement status of adult lymphoma, high sensitivity and specificity are observed by RFS, and high concordance is also noted with both IHC and FCM. Thus, the BM infiltrating status of adult lymphoma could be evaluated more accurately by a combined usage of the three methods.

Aim To explore the correlation between carotid atherosclerosis(CAS)and neutrophil/lymphocyte ratio(NLR)in patients with early morning hypertension,and to construct a line chart model to predict the risk of CAS in patients with hypertension in the morning.Methods 255 patients with early morning hypertension hospitalized in the Affiliated Hospital of Chengde Medical College from October 2019 to November 2022 were collected,and their basic data,blood routine and blood biochemical indexes were collected.All selected patients need to improve 24-hour ambulatory blood pressure monitoring and carotid artery color ultrasound detection.According to the presence or absence of CAS,all selected patients were divided into morning hypertension with CAS group(n=197)and morning hypertension without CAS group(n=58).Multivariate Logistic regression analysis was used to explore the risk factors of early morning hypertension with CAS,and to construct and verify an individual line chart model to predict the risk of early morning hypertension pa-tients with CAS.Results The age,NLR,neutrophils(NE),monocytes(MO),white blood cell(WBC),total cho-lesterol(TC),triglyceride(TG)and low density lipoprotein cholesterol(LDLC)increased in the early morning hyperten-sion with CAS group compared with those in the morning hypertension group without CAS,while the HDLC decreased(P＜0.05).The results of multivariate Logistic regression analysis showed that the age,NLR and TC were higher in the early morning hypertension with CAS group than those in the early morning hypertension without CAS group,while HDLC was lower;Age,NLR and TC were independent risk factors of early morning hypertension with CAS,while HDLC was inde-pendent protective factors of morning hypertension with CAS.Based on the results of multivariate Logistic regression anal-ysis,an individualized line chart model for predicting early morning hypertension with CAS was constructed.The area un-der the ROC curve of the line chart model was 0.853(95％CI:0.802-0.904,P＜0.01).The result of Hosmer Leme-show fit test was x2=1.665(P＞0.05).Conclusions There was a positive correlation between NLR and morning hy-pertension with CAS,and NLR was an independent risk factor for morning hypertension with CAS.The individualized line chart model based on age,NLR,TC and HDLC can effectively predict the risk of hypertension with CAS in the early morn-ing,which provides a theoretical basis for early detection and prevention of atherosclerosis.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death, and most patients with HCC are diagnosed at an advanced stage. Before 2017, tyrosine kinase inhibitors were the main drugs for the treatment of advanced hepatocellular carcinoma. With the emergence of immune checkpoint inhibitors (ICIs), immunotherapy has gradually brought new hope to such patients. At present, the combination of ICIs and other systemic or local treatments has become a potential strategy for the treatment of advanced hepatocellular carcinoma, and some of these combinations have been included in large-scale clinical trials. The main challenges of immunotherapy for advanced hepatocellular carcinoma include the exploration of predictive biomarkers, management of immune-related adverse events, and exploration of effective combination regimens. This article provides the latest research progress on the single or combined use of ICIs and other immunotherapy for hepatocellular carcinoma and discusses the limitations of current research and clinical application and the future development direction.

Objective:To construct and validate a predictive model for the occurrence of malignant cerebral edema(MCE)in the elderly with acute large hemispheric infarction(LHI)of the anterior cerebral artery.Methods:Clinical, laboratory and imaging data of 301 elderly patients with acute LHI of the anterior cerebral artery admitted to the Department of Neurology of the Third Affiliated Hospital of Soochow University between January 2018 and April 2023 were retrospectively analyzed.Patients were divided into a modeling group(211 cases)and a validation group(90 cases)by the simple random sampling method with a ratio of 7∶3.According to the occurrence of MCE, univariate and multivariate Logistic regression analyses were performed with data from the modeling group to screen for independent predictors of the development of MCE.Nomograms were created and internally validated using R software.Additionally, external validation was performed with data from the validation group, and the performance of the model was assessed by receiver operating characteristic(ROC)curves, calibration plots, and clinical decision curve analysis(DCA), respectively.Results:The MCE incidence and baseline data between the modeling and validation groups were not statistically significantly different and were actually comparable.Multivariate Logistic analysis in the modeling group showed that a history of atrial fibrillation( OR=3.459, 95% CI: 1.202-9.955, P=0.021), Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score( OR=1.202, 95% CI: 1.052-1.373, P=0.007), National Institutes of Health Stroke Scale(NIHSS)score( OR=1.163, 95% CI: 1.039-1.3013, P=0.008), Alberta Stroke Program Early CT Score(ASPECTS)( OR=0.782, 95% CI: 0.639-0.958, P=0.018), and collateral score(CS)( OR=0.414, 95% CI: 0.221-0.777, P=0.006)were independent predictors of the occurrence of MCE in the elderly patients with LHI.Based on the nomogram model constructed using the independent predictors, the ROC value for the risk of developing MCE was 0.912(95% CI: 0.867-0.957)in the modeling group and 0.957(95% CI: 0.902-0.997)in the validation group.The predicted probabilities from the nomograms in the modeling and validation groups were close to the actual probabilities, indicating good calibration.The DCA curves in the validation group showed that the predictive model had good clinical utility. Conclusions:The nomogram model established in this study exhibits good discrimination and calibration for the prediction of MCE, and has some predictive value.

Objective:To explore the effect of abdominal massage on the behavior of rats with neonatal hypoxia-ischemia and its mechanism.Methods:7-day-old SD rats were made as the HIBD model by the classical method of RICE and then the HIBD model rats were divided into the abdominal massage group and model group according to the random number table method, with 12 rats in each group, and 12 rats were selected as the normal group. The abdominal massage group was given abdominal massage 24 hours after the modeling, and the intervention continued for 28 days. Rats in each group underwent a balance beam test on the 7th, 14th, 21st, and 28th day of the intervention. After the intervention, HE staining was applied to observe the morphological structure of the hippocampal CA1 region of the rats; Quantitative Real-time PCR method was used to measure the serotonin receptor (5-HTR1A) in the hippocampus. The expression of cAMP, PKA and CREB in the hippocampus were measured by immunohistochemistry, and the expression of SYP protein was measured by Western blotting.Results:After the intervention, the cells in the hippocampal CA1 area of the model group were diffusely distributed, the number of neurons reduced, and the condition of inflammatory edema appeared; the cells in hippocampal CA1 area of the abdominal massage group were arranged clearly, and the condition of inflammatory edema has significantly improved; on the 21st and 28th day of the intervention, the balance beam test scores in the abdominal massage group significantly decreased ( P<0.05), and the relative expression of 5-HTR1A mRNA (1.18±0.08 vs. 0.77±0.04) in the abdominal massage group significantly increased ( P<0.05). The expression of cAMP (0.32±0.02 vs. 0.31±0.01), PKA (0.32±0.02 vs. 0.29±0.01),CREB (0.31±0.02 vs. 0.28±0.01) and SYP in the abdominal massage group significantly increased ( P<0.05). Conclusion:Abdominal massage could improve the behavior of neonatal hypoxic-ischemic rats, which may play a role on nerve repair by regulating 5-HTR1A/cAMP/PKA signaling pathway.