Objective:To evaluate the efficacy and safety of upadacitinib in the real-world treatment of difficult-to-treat Crohn's disease (DTT-CD) .Methods:This multicenter, retrospective cohort study included patients diagnosed with DTT-CD according to the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) criteria, and treated at eight Chinese inflammatory bowel disease centers between January 2023 and March 2025. Clinical outcomes were assessed after 12 weeks of induction therapy with upadacitinib (45 mg qd), including clinical remission rate, clinical response rate, and incidence of adverse events.Results:Among 151 enrolled DTT-CD patients, the clinical remission rate was 47.0%, and the clinical response rate was 90.7% after 12 weeks of treatment. Adverse events occurred in 42 cases (27.8%) .Conclusion:Upadacitinib demonstrated favorable efficacy in inducing clinical remission in DTT-CD patients, with a good safety profile at the induction dose (45 mg qd) .

Objective:To evaluate the efficacy and safety of upadacitinib in the real-world treatment of difficult-to-treat Crohn's disease (DTT-CD) .Methods:This multicenter, retrospective cohort study included patients diagnosed with DTT-CD according to the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) criteria, and treated at eight Chinese inflammatory bowel disease centers between January 2023 and March 2025. Clinical outcomes were assessed after 12 weeks of induction therapy with upadacitinib (45 mg qd), including clinical remission rate, clinical response rate, and incidence of adverse events.Results:Among 151 enrolled DTT-CD patients, the clinical remission rate was 47.0%, and the clinical response rate was 90.7% after 12 weeks of treatment. Adverse events occurred in 42 cases (27.8%) .Conclusion:Upadacitinib demonstrated favorable efficacy in inducing clinical remission in DTT-CD patients, with a good safety profile at the induction dose (45 mg qd) .

Objective:To analyze the relationship between aquaporin 1 (AQP1) level and vascular calcification in patients with diabetes nephropathy.Methods:A total of 125 diabetic nephropathy patients admitted to Suzhou Hospital of Nanjing Medical University from March 2020 to March 2023 were retrospectively selected as case group. The case group was divided into group A (diabetes nephropathy stage Ⅰ and Ⅱ) with 31 cases, group B (diabetes nephropathy stage Ⅲ) with 32 cases, group C (diabetes nephropathy stage Ⅳ) with 39 cases, and group D (diabetes nephropathy stage V) with 23 cases. In these patients, 51 cases had vascular calcification, taken as the calcification group, and 74 cases had no vascular calcification, taken as the non calcification group. Sixty volunteers who underwent health examinations in the same hospital were selected as the control group. Receiver operating characteristic curve was used to analyze the predictive value of AQP1 on vascular calcification in diabetes nephropathy patients and to explore the related factors of vascular calcification in diabetes nephropathy patients.Results:Compared with the control group, AQP1 level and calcification rate in groups A, B, C and D were higher: 6.41 ± 1.04, 7.93 ± 1.23, 9.50 ± 1.52 and 11.37 ± 2.01 vs. 3.83 ± 0.56 ng/L, 6.45% (2/31), 28.13% (9/32), 51.28% (20/29) and 86.96% (20/23) vs. 0 ( P<0.05). Compared with group A, the level of AQP1 and calcification rate in groups B, C and D were higher ( P<0.05); compared with group B, the AQP1 level and calcification rate in groups C and D were higher ( P<0.05); compared with group C, the level of AQP1 and calcification rate in group D were higher ( P<0.05). Compared to the non calcification group, the levels of uric acid, homocysteine and cystatin C in calcification group were higher: (313.82 ± 38.72) μmol/L vs. (253.42 ± 30.14) μmol/L, (20.03 ± 3.01) μmol/L vs. (15.01 ± 2.71) μmol/L, (1.73 ± 0.26) mg/L vs. (1.30 ± 0.17) mg/L ( P<0.05). AQP1 was positively correlated with uric acid, homocysteine, and cystatin C ( P<0.05). The area under the curve of AQP1, uric acid, homocysteine and cystatin C in predicting vascular calcification in patients with diabetes nephropathy were 0.892, 0.803, 0.738 and 0.763, respectively. Taking whether vascular calcification occurs in patients with diabetes nephropathy as the dependent variable (no = 0, yes = 1), the variables of P<0.05 in the single factor analysis were selected for multivariate Logistic regression analysis. The results showed that uric acid, homocysteine, cystatin C and AQP1 were the main factors affecting vascular calcification in patients with diabetes nephropathy ( P<0.05). Conclusions:Serum AQP1 has a high predictive value for vascular calcification in diabetes nephropathy patients, and is expected to be used as a biomarker for early diagnosis of vascular calcification in diabetes nephropathy patients.

OBJECTIVE: To evaluate the value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for assessing disease activity in patients with rheumatoid arthritis (RA) treated with tofacitinib. METHODS: This retrospective study was conducted among 98 RA patients in active stage treated with tofacitinib in Third Xiangya Hospital and 100 healthy control subjects from the Health Management Center of the hospital from 2019 to 2021. We collected blood samples from all the participants for measurement of erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and other blood parameters 1 month before and 6 months after tofacitinib treatment. We further evaluated PLR and NLR before and after tofacitinib treatment in the RA patients, and analyzed their correlations with RA disease activity. RESULTS: PLR and NLR increased significantly in RA patients as compared with the healthy controls. In the RA patients, PLR and NLR were positively correlated with the levels of hs- CRP, ESR, IL- 6, Disease Activity Score of 28 joints-ESR (DAS28-ESR), anti-cyclic citrullinated peptide (CCP), and rheumatoid factor (RF) before and after tofacitinib treatment. Tofacitinib treatment for 6 months significantly decreased hs-CRP, ESR, IL-6, CCP, RF and DAS28-ESR levels in the RA patients. CONCLUSION NLR and PLR can be useful biomarkers for assessing disease activity in RA patients treated with tofacitinib.
Humans ; Neutrophils ; Retrospective Studies ; C-Reactive Protein/analysis* ; Interleukin-6/metabolism* ; Arthritis, Rheumatoid ; Lymphocytes

Objective:To investigate the c-Jun N-terminal kinase (JNK), CCAAT/enhancer-binding protein homologous protein (CHOP) pathway apoptosis and the changes of cytokine levels in immune-related organs and tissues of sepsis mice at different time points.Methods:Twenty-seven male BALB/c mice were divided into normal group, sepsis 6 hours group and sepsis 12 hours group by the block randomization method, with 9 mice in each group. The sepsis model was made by cecal ligation and puncture (CLP). Blood sample was collected from each group at the corresponding time point, and the serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL-1β, IL-10) were measured by enzyme linked immunosorbent assay (ELISA). The spleen, thymus and appendix tissues were taken from the mice to detect the expressions of phosphorylation-JNK (p-JNK), JNK1, CHOP and cleaved caspase-3 protein by Western Blot.Results:The level of cytokines, p-JNK/JNK1 ratio, CHOP and caspase-3 in spleen tissues, and the CHOP, caspase-3 in thymus and appendix tissue in the sepsis 6 hours group were significantly higher than those in the normal group [serum TNF-α (ng/L): 24.29±3.09 vs. 2.93±2.09, serum IL-1β (ng/L): 5.00±3.19 vs. 3.54±1.53, serum IL-10 (ng/L): 1 963.93±270.20 vs. 275.09±45.21, spleen p-JNK/JNK1 ratio: 0.257±0.126 vs. 0.154±0.068, spleen CHOP/β-actin: 0.201±0.131 vs. 0.142±0.068, spleen caspase-3/β-actin: 0.215±0.126 vs. 0.098±0.088, thymus CHOP/β-actin: 0.122±0.071 vs. 0.089±0.067, thymus caspase-3/β-actin: 0.258±0.145 vs. 0.108±0.045, appendix CHOP/β-actin: 0.361±0.134 vs. 0.215±0.112, appendix caspase-3/β-actin: 0.439±0.211 vs. 0.321±0.145, all P < 0.05]. However, there were no significant difference in the p-JNK/JNK1 ratio in thymus and appendix (thymus p-JNK/JNK1 ratio: 1.221±0.776 vs. 1.168±0.475, appendix p-JNK/JNK1 ratio: 2.014±1.227 vs. 1.828±0.915, both P > 0.05). Cytokine levels and the p-JNK/JNK1 ratio, CHOP, caspase-3 in spleen, thymus, and appendix in the sepsis 12 hours group were further increased when compared with those in the sepsis 6 hours group, except for a significant decrease in IL-10 level [serum IL-10 (ng/L): 1 698.98±210.52 vs. 1 963.93±270.20, serum TNF-α (ng/L): 41.66±6.57 vs. 24.29±3.09, serum IL-1β (ng/L): 10.37±4.14 vs. 5.00±3.19, spleen p-JNK/JNK1 ratio: 0.399±0.135 vs. 0.257±0.126, spleen CHOP/β-actin: 0.298±0.145 vs. 0.201±0.131, spleen caspase-3/β-actin: 0.353±0.145 vs. 0.215±0.126, thymus p-JNK/JNK1 ratio: 1.667±0.891 vs. 1.221±0.776, thymus CHOP/β-actin: 0.207±0.133 vs. 0.122±0.071, thymus caspase-3/β-actin: 0.416±0.179 vs. 0.258±0.145, appendix p-JNK/JNK1 ratio: 2.425±1.361 vs. 2.014±1.227, appendix CHOP/β-actin: 0.456±0.189 vs. 0.361±0.134, appendix caspase-3/β-actin: 0.635±0.289 vs. 0.439±0.211, all P < 0.05]. Conclusions:The endoplasmic reticulum pathway JNK and CHOP pathways are involved in immune-related cell apoptosis and cytokine expression in mice with sepsis. Apoptosis is more obvious at 12 hours than at 6 hours, and the inflammatory response is stronger.

Hypertension with high serum Homocysteine (Hcy) significantly increases the incidence of cardiovascular and cerebrovascular events, which is defined as H-Type Hypertension by Chinese scholars. Plenty of researches have confirmed that high prevalence of H-Type Hypertension in Chinese population is now the big public problem in China. Traditional Chinese Medicine(TCM)treatment shows the advantages in integral regulation, less side effect, and anti-Hcy effect in hypertension. This paper discussed the prevalence, TCM syndrome and TCM treatment progress in H-Type Hypertension to provide some ideas and references for the intervention of H-Type Hypertension by TCM.

OBJECTIVE To explore the effect of aqueous extract of Zheng Chaihu Yin(ZCH)on paracetamol(acetaminophen,APAP)-induced hepatotoxicity. METHODS Male ICR mice were divided into three scenarios randomly:the single treatment dose of ZCH,multiple treatment or pretreatment dose of ZCH. Each scenario had a up control group and an APAP model group,while single treatment dose of ZCH group had a ZCH group at the same time. The dose of APAP and ZCH was 500 mg·kg-1 and 36 g · kg- 1,respectively. 24 h after the last administration,plasma and liver samples were prepared. Ultra- performance liquid chromatography/quadrupole- time- of- flight mass spectrometry (UPLC-Q-TOF-MS)based metabolomics profiling was used to examine changes in plasma after expo?sure to ZCH,APAP or co-exposure to ZCH and APAP. Glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminas (GOT) values were determined by a biochemical auto analyzer in plasma. Histopathologic changes in the liver were observed and the area was calculated after HE staining. The data were analyzed with SPSS16.0 statistical software and the results were compared with the test between the two groups to find biomarkers. Also,SIMCA software was used for partial least squares-discriminant analysis (PLS-DA) pattern recognition. RESULTS Compared to control group, APAP dosing alone caused an increase in plasma transaminases and alterations in multiple metabolic pathways. Compared to APAP group,decrease in plasma transaminases was noted when ZCH was administered after or prior to APAP. Histopathologic results showed that in the single treatment group, multiple treatment group and pretreatment group,ZCH could alleviate the liver damage induced by APAP from (32.3 ± 12.0)% to (14.2 ± 9.9)%,(8.6 ± 7.9)% to (5.2 ± 1.7)% and (32.5 ± 10.0)% to (5.2 ± 6.4)%(P<0.05). Similarly,the PLS-DA of the LC-MS data showed that the groups dosed with APAP alone were the most distinct from controls,while animals dosed with ZCH prior to or after APAP treatment were located near control group. Metabolic spectrum results showed that ZCH could restore the changes in endogenous substances including lipid metabolism,amino acid metabolism,sugar metabolism and energy metabolism induced by APAP to normal. CONCLUSION ZCH water-extraction plays major roles in the regulation of metabolism on APAP-induced liver injury. These studies demonstrate that UPLC-Q-TOF-MS-based metabolomic analysis can be sensitively and accurately predict the initiation and progres?sion of liver injury and greatly contribute to a better understanding of the hepatoprotective effects of ZCH in a clinical environment.

Aim To investigate the effect of Rhein on the movement and invasiveness of human ovarian carci-noma cells with directional high lymphatic metastasis SKOV3-PM4 cells and explore the role of Rac1/LIMK1/cofilin signaling pathway. Methods Migration assay and invasion assay were used to observe the effect of Rhein on the metastatic and invasive ability of SK-OV3-PM4 cells in vitro. The effect of Rhein on the morphology and cytoskeleton ultrastructure of ovarian cancer cells was observed by laser scanning confocal microscope and scanning electron microscope. The protein expression level of Rac1,LIMK1,PAK1 and co-filin were detected by Western blot, respectively. Re-sults Rhein inhibited the abilities of cell invasion and migration of SKOV3-PM4 cells,and the inhibitory rate increased along with the increase of the concentration and treatment duration. After treated with 8. 80 μmol· L-1 ,17. 60 μmol · L-1 , 26. 40 μmol · L-1 of Rhein for 24 h,the abilities of migration and invasion of SK-OV3-PM4 cells were inhibited ( P <0. 05 ); the mor-phology and cytoskeleton ultrastructure of SKOV3-PM4 cells were changed, cellular pseudopod reduced, cell microfilament fractured and its distribution disordered, plasma membrane was uneven and cell gap widened . After treatment of Rhein and Rac1 inhibitor , Rac1 protein expression and the expression of P-LIMK1 , P-PAK1 and P-cofilin notably decreased in a dose-de-pendent manner compared with the control group ( P<0. 05 ) . After Rhein and Rhein plus Rac1 inhibitor treatment ,P-LIMK1, P-cofilin, P-PAK1 protein levels of SKOV3-PM4 cells significantly decreased compared with the control group , and the group of Rac1 inhibi-tor plus Rhein treatment, the phosphorylated protein decreased more significantly ( P <0. 05 ) . After Rac1 activator plus Rhein treatment, phosphorylated protein expression of P-LIMK1 ,P-PAK1 and P-cofilin upregu-lated significantly ( P <0. 05 ) . Conclusions Rhein may be a potential inhibitor of Rac1 and can inhibit the migrating and invasive capabilities of directional high lymphatic metastasis SKOV3-PM4 cells through down-regulating the phosphorylation of Rac1/LIMK1 /cofilin pathway associated protein.

Objective To explore the psychosocial influencing factors of suicide attitudes among new recruits in training camp.Methods Cluster sampling was conducted and 5 200 new recruits in 11 training camps were investigated with suicide attitude questionnaire(QSA),symptom checklist 90(SCL-90) and self-designed questionnaire.Influencing factors associated with suicide attitudes were analyzed with muhiple linear regression analysis.Results The score of awareness of property of suicide behavior dimension of QSA were (3.71±0.58),and (2.77±0.47) of the attitude to the suicide dimension,(2.43±0.43) of the attitude to family members of the suicide dimension and (3.13±0.86) of the attitude to euthanasia dimension.The results of multiple linear regression analysis indicated that recruits who came from single parent family,had a history of family violence,had a introvert character,had poor emotional stability,had a history of psychiatrist visiting,took Sedatives more often,had more negative life events in past year,tended to use unhealthy cathartic method of emotion,had more difficulty in adjusting to the army life,had lower factor score of obsessivecompulsive symptoms in SCL-90,and higher factor score of depression and paranoia,tended to hold an admissive attitude to suicide behavior.Conclusion The recruits in training camp don' t accept suicide behavior as a whole,and their suicide attitudes were influenced by mental health states and many other psychosocial factors.Suicide prevention education should be targeted.

Objective To assess the application of Chinese children's intelligence equation (CCIE) and Bayley Scales of infant and toddler development-Ⅲ (BSID-Ⅲ) in screening of postoperative cognitive dysfunction (POCD) in children after general anesthesia.Methods The study group (Group A),including 50 ASA-Ⅰ participants of 1-3 years old who would undergo hernia repair laparoscopic surgery,was assessed on one day (1 d) before and three days (3d) after the surgery respectively by both of CCIE and BSID-Ⅲ according to their ages of month.The control group (Group C),including 50 healthy participants with the matched age,was assessed in the same period by the same method.Both of Group A and C were assessed by the Z score method to diagnose POCD and both scales were used to analyze the results of POCD screening and their agreement.Results (1) Compared with preoperative 1 d,the CCIE score of Group A on 3d after surgery was relatively decreased (21.22±4.96 vs 18.65±4.74,P＜0.05) and the POCD rate was 12.0％.While in Group C,the CCIE score and the POCD rate had no statistical significance (20.83±4.97 vs 21.22±5.21,P＞0.05).(2) Compared with preoperative 1d,the scores of cognition,language,motion,social-emotion and adaptive behaviors in BSID-Ⅲ of Group A decreased (100.00±4.58 vs 96.44± 4.20,103.22±4.99 vs 96.24± 5.75,102.06±4.01 vs 95.28±4.27,101.22±7.38 vs 91.06±7.10,98.52±9.11 vs 90.5±8.47,P＜0.05) and the POCD incidence was 20.0％.While in group C,the BSID-Ⅲ score and the POCD rate had no statistical significance (104.61±5.48 vs 103.79±5.38,107.68±5.60 vs 107.11 ±6.05,108.29±5.91 vs 108.29±4.21,101.11±7.61 vs 101.86±6.99,99.00±7.99 vs 100.82±7.36,P＞0.05).(3)Reasonable agreement of the CCIE and BSID-Ⅲ was observed (Kappa value was 0.70;P＜ 0.05).Conclusion There is considerable agreement between BSID-Ⅲ and CCIE.While BSID-Ⅲ is relatively more sensitive to the POCD and more efficient in the diagnosis of POCD than the CCIE.Thus,BSID-Ⅲ is more likely to provide better evaluation of the postoperative cognitive functions of children within 1-3 years old and should be recommended to the health professionals in China.