Objective To analyse and explore whether there is a causal association without confounding factors between malignant haematological diseases and frailty based on a bidirectional Mendelian randomisation(MR)analysis,and to provide a theoretical basis for clinical management of the frailty associated with malignant haematological diseases.Methods In December 2023,the IEU OpenGWAS database(https://gwas.mrcieu.ac.uk/)was searched to acquire the datasets in genome-wide association studies(GWAS)derived from non-overlapping multi-ethnic populations based on Mendelian Randomisation(MR)analysis.The bidirectional causal association was verified utilising the two-sample MR approach.Single nucleotide polymorphisms(SNPs)of the frailty index(FI)(n=175,226),haematological malignancies(n=212,453),multiple myeloma/malignant plasmacytoma(n=218,792),and follicular lymphoma(n=181,278)were used as the study instruments.Results The analysis with the statistic inverse variance weighted method(IVW)showed that haematological malignancies(OR=1.00,95%CI:0.98-1.00,P=0.797),multiple myeloma/malignant plasma cell tumours(OR=1.00,95%CI 0.99～1.01,P=0.982),and follicular lymphoma(OR=1.00,95%CI:0.99～1.01,P=0.314)were not causally associated with genetically predicted FI.Similarly,FI was not significantly or causally correlated with haematological malignancies(OR=0.89,95%CI:0.25～3.12,P=0.861),multiple myeloma/malignant plasma cell tumours(OR=0.52,95%CI:0.00～3.13,P=0.473),and follicular lymphoma(OR=1.06,95%CI:0.00～5.19,P=0.944).Conclusion No causal relationship between the malignant haematological diseases and frailty was found in this study.It suggests that other factors might exist to cause the malignant haematological frailty.

AIM:This study aims to investigate the functions of interleukin-6(IL-6)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway in adenomyosis(ADM),and to assess the therapeutic potential of JAK2 inhibitor AG490.METHODS:(1)Neonatal female mice were randomly divided into 2 groups:control group and ADM group.An ADM mice model was established by tamoxifen.Additionally,Western blot was employed to detect the expression of IL-6/JAK2/STAT3 signaling pathway-related proteins.(2)Human endometrial adenocarcinoma Ishikawa cells were treated with AG490,and Western blot was performed to evaluate the expression of the proteins related to IL-6/JAK2/STAT3 signaling pathway,epithelial-mesenchymal transition(EMT),cell migration and cell proliferation.Besides,wound-healing and Transwell assays were carried out to investigate the cell migration and inva-sion.Colony formation and EdU assays were employed to investigate the cell proliferation,and flow cytometry analysis was performed to investigate the cell apoptosis.(3)The ADM mice were randomly divided into 2 groups:ADM group and AG490 group.The expression of IL-6/JAK2/STAT3 signaling pathway-related proteins in uterine tissues was detected by Western blot.Besides,Western blot and immunohistochemistry were employed to detect the expression of the proteins re-lated to cell EMT,migration and proliferation.Cell apoptosis in uterine tissues was detected by TUNEL assay.RE-SULTS:(1)The expression of IL-6/JAK2/STAT3 signaling pathway-related proteins exhibited an increasing trend in ADM mice(P<0.05).(2)Treatment with AG490 significantly suppressed the expression of IL-6/JAK2/STAT3 signaling pathway-related proteins in Ishikawa cells(P<0.05).The protein level of E-cadherin showed an increasing trend(P<0.01),while the expression levels of N-cadherin,vimentin and Slug showed a decreasing trend(P<0.05)in Ishikawa cells after AG490 treatment.Besides,the expression of MMP-2 and MMP-9 was down-regulated(P<0.05),and the capa-bilities of cell migration and invasion were suppressed in AG490-treated Ishikawa cells(P<0.05).The expression levels of Bcl-2 and cyclin D1 exhibited a decreasing trend(P<0.05),and the expression level of Bax increased(P<0.05)in Ishikawa cells after treatment with AG490.Additionally,AG490 inhibited Ishikawa cell proliferation,and enhanced the cell apoptosis(P<0.01).(3)The p-JAK2/JAK ratio and the IL-6 expression exhibited a decreasing trend in AG490 group(P<0.01).Moreover,the expression of E-cadherin was up-regulated(P<0.05),while the expression of N-cadherin,vi-mentin,Snail,Slug and Twist was down-regulated(P<0.05)in ADM mice after treatment with AG490.Compared with ADM group,the expression of MMP-2 and MMP-9 decreased in AG490 group(P<0.05),alongside the down-regulated Bcl-2/Bax ratio and PCNA expression(P<0.01).Besides,the cell apoptosis was enhanced by AG490.CONCLUSION:The IL-6/JAK2/STAT3 signaling pathway is aberrantly activated in ADM and facilitates endometrial cell EMT,prolifera-tion,invasion and migration.Additionally,AG490 inhibits the progression of ADM by blocking the IL-6/JAK2/STAT3 sig-naling pathway.

AIM:This study aims to investigate the functions of interleukin-6(IL-6)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway in adenomyosis(ADM),and to assess the therapeutic potential of JAK2 inhibitor AG490.METHODS:(1)Neonatal female mice were randomly divided into 2 groups:control group and ADM group.An ADM mice model was established by tamoxifen.Additionally,Western blot was employed to detect the expression of IL-6/JAK2/STAT3 signaling pathway-related proteins.(2)Human endometrial adenocarcinoma Ishikawa cells were treated with AG490,and Western blot was performed to evaluate the expression of the proteins related to IL-6/JAK2/STAT3 signaling pathway,epithelial-mesenchymal transition(EMT),cell migration and cell proliferation.Besides,wound-healing and Transwell assays were carried out to investigate the cell migration and inva-sion.Colony formation and EdU assays were employed to investigate the cell proliferation,and flow cytometry analysis was performed to investigate the cell apoptosis.(3)The ADM mice were randomly divided into 2 groups:ADM group and AG490 group.The expression of IL-6/JAK2/STAT3 signaling pathway-related proteins in uterine tissues was detected by Western blot.Besides,Western blot and immunohistochemistry were employed to detect the expression of the proteins re-lated to cell EMT,migration and proliferation.Cell apoptosis in uterine tissues was detected by TUNEL assay.RE-SULTS:(1)The expression of IL-6/JAK2/STAT3 signaling pathway-related proteins exhibited an increasing trend in ADM mice(P<0.05).(2)Treatment with AG490 significantly suppressed the expression of IL-6/JAK2/STAT3 signaling pathway-related proteins in Ishikawa cells(P<0.05).The protein level of E-cadherin showed an increasing trend(P<0.01),while the expression levels of N-cadherin,vimentin and Slug showed a decreasing trend(P<0.05)in Ishikawa cells after AG490 treatment.Besides,the expression of MMP-2 and MMP-9 was down-regulated(P<0.05),and the capa-bilities of cell migration and invasion were suppressed in AG490-treated Ishikawa cells(P<0.05).The expression levels of Bcl-2 and cyclin D1 exhibited a decreasing trend(P<0.05),and the expression level of Bax increased(P<0.05)in Ishikawa cells after treatment with AG490.Additionally,AG490 inhibited Ishikawa cell proliferation,and enhanced the cell apoptosis(P<0.01).(3)The p-JAK2/JAK ratio and the IL-6 expression exhibited a decreasing trend in AG490 group(P<0.01).Moreover,the expression of E-cadherin was up-regulated(P<0.05),while the expression of N-cadherin,vi-mentin,Snail,Slug and Twist was down-regulated(P<0.05)in ADM mice after treatment with AG490.Compared with ADM group,the expression of MMP-2 and MMP-9 decreased in AG490 group(P<0.05),alongside the down-regulated Bcl-2/Bax ratio and PCNA expression(P<0.01).Besides,the cell apoptosis was enhanced by AG490.CONCLUSION:The IL-6/JAK2/STAT3 signaling pathway is aberrantly activated in ADM and facilitates endometrial cell EMT,prolifera-tion,invasion and migration.Additionally,AG490 inhibits the progression of ADM by blocking the IL-6/JAK2/STAT3 sig-naling pathway.

Objective To analyse and explore whether there is a causal association without confounding factors between malignant haematological diseases and frailty based on a bidirectional Mendelian randomisation(MR)analysis,and to provide a theoretical basis for clinical management of the frailty associated with malignant haematological diseases.Methods In December 2023,the IEU OpenGWAS database(https://gwas.mrcieu.ac.uk/)was searched to acquire the datasets in genome-wide association studies(GWAS)derived from non-overlapping multi-ethnic populations based on Mendelian Randomisation(MR)analysis.The bidirectional causal association was verified utilising the two-sample MR approach.Single nucleotide polymorphisms(SNPs)of the frailty index(FI)(n=175,226),haematological malignancies(n=212,453),multiple myeloma/malignant plasmacytoma(n=218,792),and follicular lymphoma(n=181,278)were used as the study instruments.Results The analysis with the statistic inverse variance weighted method(IVW)showed that haematological malignancies(OR=1.00,95%CI:0.98-1.00,P=0.797),multiple myeloma/malignant plasma cell tumours(OR=1.00,95%CI 0.99～1.01,P=0.982),and follicular lymphoma(OR=1.00,95%CI:0.99～1.01,P=0.314)were not causally associated with genetically predicted FI.Similarly,FI was not significantly or causally correlated with haematological malignancies(OR=0.89,95%CI:0.25～3.12,P=0.861),multiple myeloma/malignant plasma cell tumours(OR=0.52,95%CI:0.00～3.13,P=0.473),and follicular lymphoma(OR=1.06,95%CI:0.00～5.19,P=0.944).Conclusion No causal relationship between the malignant haematological diseases and frailty was found in this study.It suggests that other factors might exist to cause the malignant haematological frailty.

OBJECTIVE To screen the potential active components of Polygonum orientale flower against myocardial ischemia- reperfusion injury （MIRI） in rats based on physiological and pathological states. METHODS SD rats were divided into normal control group， normal administration group， MIRI control group and MIRI administration group， with 5 rats in each group. After drug intervention or modeling and drug intervention， chromatographic separation plasma samples were collected， and chromatographic separation and mass spectrometry data collection were performed by using UPLC-Q-TOF/MS. The prototype components and metabolites were analyzed by comparing the reference substance maps， the maps of each plasma sample， and the relevant literature. At the same time， the common peaks in plasma samples of rats in normal administration group and MIRI administration group were identified. Combined with principal component analysis and orthogonal partial least square-discriminant analysis， the differential transitional components were screened out according to the value of variable importance in the projection （VIP）＞1， to speculate the potential active components of P. orientale flower in rats under physiological and pathological states. The SD rats were divided into control group， MIRI group， positive control group （Compound danshen tablets 0.2 g/kg， 3 times a day）， and potentially active compound groups （10 mg/kg， twice a day）， with 5 rats in each group. The rats in administration groups were given relevant medicine intragastrically， for 3 consecutive days. The activity of superoxide dismutase （SOD）， the leakages of lactate dehydrogenase （LDH）， creatine kinase isoenzyme-MB （CK-MB） and cardiac troponin Ⅰ （cTnⅠ） in plasma were detected after the last administration. RESULTS Twenty-six main chromatographic peaks were obtained from the total ion chromatogram of the extract of P. orientale flower， and 14 of them were determined， including gallic acid， catechin， protocatechuic acid and so on. There were fifteen （including 6 absorbed prototype components and 9 metabolites） and nineteen transitional components （including 6 absorbed prototype components and 13 metabolites） in the plasma sample of normal rats and MIRI rats. Eight transitional components were detected in both normal rats and MIRI rats， and the VIP values of kaempferol glucuronidation metabolites， quercetin carbonylation metabolites and N-p-paprazine to the corresponding peak were higher than 1. Compared with MIRI group， the activities of SOD were increased significantly in the plasma of MIRI rats in each potential active compound group （P＜0.01）， and the leakages of LDH， CK-MB， and cTnⅠ in the plasma of MIRI rats were reduced significantly （P＜0.01）. CONCLUSIONS The potential anti-MIRI active components in extract of P. orientale flower are N-p-paprazine， quercetin， kaempferol and kaempferol-3-O-β-D-glucoside.

Objective:To investigate the relationship and assess the value of serum polyadenosine diphosphate ribose polymerase 1 (PARP1) and forkhead box transcription factor O1 (FOXO1) with cerebral neurological function in patients with severe craniocerebral injury (SCI).Methods:The clinical data of 100 patients with SCI from February 2021 to October 2022 in Baoji High-Tech Hospital were retrospectively analyzed. The Glasgow coma score (GCS) on admission was recorded. According to the modified Rankin score (mRS) 3 months after discharge, the patients were divided into good recovery group (mRS 0 to 2 scores, 62 cases) and poor recovery group (mRS 3 to 5 scores, 38 cases). In addition, 50 individuals who underwent physical examinations in Baoji High-Tech Hospital during the same period were selected as the control group. The serum levels of PARP1 and FOXO1 were measured by enzyme-linked immunosorbent assay. Correlation analysis was performed using Spearman method. Multifactor Logistic regression was used to analyze the independent risk factors for poor cerebral neurological recovery in patients with SCI. The efficacy of PARP1 and FOXO1 in predicting the poor cerebral neurological recovery in patients with SCI was evaluated by the receiver operating characteristic (ROC) curve.Results:The PARP1 and FOXO1 in good recovery group and poor recovery group were significantly higher than those in control group: (4.14 ± 1.19) and (5.98 ± 1.02) μg/L vs. (2.13 ± 0.71) μg/L, (5.83 ± 1.22) and (7.57 ± 3.12) μg/L vs. (4.23 ± 1.34) μg/L, the indexes in poor recovery group were significantly higher than those in good recovery group, and there were statistical differences ( P<0.05). The mRS in poor recovery group was significantly higher than that in good recovery group: (3.92 ± 0.87) scores vs. (1.03 ± 0.80) scores, and there was statistical difference ( P<0.05). Spearman correlation analysis result showed that PARP1 and FOXO1 were positively correlated with mRS score in patients with SCI ( r = 0.673 and 0.646, P<0.05). Multifactor Logistic regression analysis result showed that the GCS, mRS, PARP1 and FOXO1 were independent risk factors for poor neurological recovery in patients with SCI ( HR = 1.039, 1.286, 1.439 and 1.389; 95% CI 1.003 to 1.076, 1.011 to 1.637, 1.029 to 2.012 and 1.009 to 1.912; P<0.05). ROC curve analysis result showed that the area under the curve (AUC) of PARP1 combination with FOXO1 in assessing poor cerebral neurological recovery in patients with SCI was significantly greater than the PARP1 and FOXO1 alone: 0.953 (95% CI 0.918 to 0.988) vs. 0.866 (95% CI 0.796 to 0.936) and 0.859 (95% CI 0.783 to 0.935), Z = 2.162 and 2.188, P = 0.031 and 0.029. Conclusions:The serum PARP1 and FOXO1 levels in patients with SCI are positively correlated with cerebral neurological recovery, and they have predictive value for cerebral neurological recovery status.

Objective:To explore the influence of substance abuse history on anxiety and depression of male prisoners during their imprisonment, and its relationship with violent behavior.Methods:A questionnaire survey was conducted among 1 455 prisoners from October to November 2019.Self-administered personal substance abuse history questionnaires were used to collect the information on substance abuse (alcohol, tobacco, and drug use). The generalized anxiety scale (GAD-7) and patient health questionnaire (PHQ-9) were used to investigate anxiety and depression.All subjects were divided into substance abuse group ( n=871) and non substance abuse group ( n=584) according to whether they had a history of substance abuse or not.SPSS 21.0 software was used for statistical analysis.The statistical methods were t-test, chi square test and Logistic regression analysis. Results:(1)The scores of GAD-7 ((4.95±5.88) vs (3.35±5.33), t=-5.407, P<0.01) and PHQ-9 ((6.69±6.50) vs (4.48±5.73), t=-6.821, P<0.01) scales in the substance abuse group were higher than those in the no-substance abuse group.(2)Somatic disease( β=0.700, OR=2.014, 95% CI=1.599-2.538, P<0.05), history of alcohol abuse( β=0.434, OR=1.543, 95% CI=1.176-2.025, P<0.05), history of tobacco abuse( β=0.387, OR=1.473, 95% CI=1.154-1.880, P<0.05), age ≤ 45( β=0.372, OR=1.450, 95% CI=1.118-1.881, P<0.05) were the risk factors of anxiety among prisoners.Somatic disease( β=0.686, OR=1.986, 95% CI=1.581-2.496, P<0.05), history of tobacco abuse( β=0.488, OR=1.629, 95% CI=1.286-2.063, P<0.05), age ≤ 45( β=0.484, OR=1.622, 95% CI=1.260-2.089, P<0.05), history of alcohol abuse( β=0.344, OR=1.410, 95% CI=1.073-1.854, P<0.05) were the risk factors of depression among prisoners.(3) Years of education ≤ 9 years( β=0.900, OR=2.459, 95% CI=1.855-3.261, P<0.05), age ≤ 45( β=0.788, OR=2.199, 95% CI=1.690~2.860, P<0.05), unmarried( β=0.683, OR=1.980, 95% CI=1.421-2.759, P<0.05), history of alcohol abuse( β=0.308, OR=1.361, 95% CI=1.053-1.758, P<0.05), history of drug abuse( β=0.557, OR=1.745, 95% CI=1.055-2.885, P<0.05) were risk factors for violent behavior of prisoners. Conclusion:The history of substance abuse may be a risk factor for anxiety and depression of prisoners during their imprisonment.Alcohol and drug abuse are both factors influencing the occurrence of violent behavior.

Objective:To explore the therapeutic effect of peroral endoscopic myotomy (POEM) for primary achalasia (AC) in patients aged over 60 years.Methods:Data of 146 patients aged ≥60 years (the elderly group) and 146 patients aged 18-59 years (the adult group) who received POEM from November 2010 to September 2019 at the Digestive Endoscopy Center of PLA General Hospital were retrospectively analyzed. Baseline data, surgery data, surgery-related complications and surgery-related efficacy were compared.Results:There was no significant difference in gender, Ling classification, HRM classification or previous treatment between the two groups ( P>0.05). All 292 patients successfully underwent POEM surgery. The clinical success (Eckardt score ≤3) rates in the elderly group and the adult group were 96.33% (105/109) and 96.77% (90/93), respectively with no significant difference between the two groups ( χ2=0.030， P>0.05). There was no significant difference in the length of myotomy between the two groups (7.09±2.49 cm VS 7.12±2.24 cm， t=0.472， P>0.05). Complications occurred in 26 cases (17.81%) in the elderly group and 21 cases (14.38%) in the adult group with no significant difference between the two groups ( χ2=0.634， P>0.05). There was no significant difference in the postoperative hospital stay (12.61±9.69 days VS 11.00±4.43 days, t=1.825, P>0.05) or the incidence of gastroesophageal reflux [43.33% (13/30) VS 51.52% (17/33), χ2=0.422, P>0.05] between the elderly group and the adult group. Conclusion:The efficacy of POEM for AC patients over 60 years old is equivalent to that of adult patients, and the incidence of complications is similar. POEM is safe and effective for AC patients over 60 years old.

Objective:To retrospectively analyze the effectiveness of Caprini thrombosis risk assessment model in assessing the risk of deep venous thrombosis (DVT) in orthopedic patients.Methods:Using the convenient sampling method, 52 orthopedic patients who were diagnosed with DVT in Anhui Provincial Hospital from April 2016 to March 2019 were selected as the DVT group. According to the ratio of 1 to 2, 104 patients with non-DVT in Department of Orthopedics were selected as the non-DVT group. The Caprini risk assessment model was used to carry out DVT risk scoring and risk classification, and the relationship between different risk grading and occurrence risk of DVT in patients was explored. Logistic regression was used to explore the risk factors of DVT in orthopedic patients.Results:The Caprini score of the DVT group was (12.25±4.26) , which was higher than (7.18±2.92) of the non-DVT group, and the difference was statistically significant ( t=7.727, P<0.01) . The difference between the DVT group and the non-DVT group in Caprini risk classification was statistically significant (χ 2=8.778, P<0.05) . In the Caprini risk classification, the risk of DVT in very high-risk patients was 7.099 (95% CI: 1.604-31.412) times higher than that in non-very high-risk patients. Logistic regression analysis showed that BMI≥25 kg/m 2, bed rest time≥72 h, lower extremity swelling, plaster/limb fixation, and selective lower extremity joint replacement surgery were 5 high-risk factors for patients with DVT ( P<0.05) . Conclusions:The Caprini risk assessment model has a good predict ability for the risk of DVT in orthopedic patients. Nursing staff can carry out targeted nursing intervention according to the high-risk factors of DVT. Stratified management of this model can also enable effective hierarchical prevention of DVT risk groups and ensure the safety of patients to the maximum extent, which is worthy of clinical application.

Animals ; Apoptosis ; Brain/metabolism* ; Male ; Phosphatidylinositol 3-Kinases/metabolism* ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage/drug therapy* ; Thyroxine/pharmacology*