OBJECTIVE To explore the antidepressant mechanism of Wenyang jieyu granules （WYJYG） via the NOD-like receptor thermal protein domain associated protein 3 （NLRP3）/apoptosis-associated speck-like protein containing a CARD （ASC）/Caspase-1 pathway. METHODS A rat model of depression was established by chronic unpredictable mild stress combined with single-housing for 42 consecutive days.The experiment set up blank group， model group， MCC950 （NLRP3 inflammasome inhibitor） group （10 mg/kg）， fluoxetine group （positive control，2.08 mg/kg），low-dose WYJYG（3.78 g/kg） and high-dose WYJYG group （7.56 g/kg），with 10 rats in each group. From the 22nd day of the experiment， rats in the fluoxetine group， low-dose and high-dose WYJYG groups were intragastrically administered with the corresponding drugs and intraperitoneally injected with an equal volume of normal saline. Rats in the MCC950 group were intraperitoneally injected with MCC950 at the corresponding concentration and intragastrically administered with an equal volume of distilled water. Rats in the blank group and model group were given an equal volume of distilled water by gavage and an equal volume of normal saline by intraperitoneal injection. All interventions were performed once a day for 21 consecutive days. Behavioral tests were conducted once a week. After the last administration， the contents of ASC， ionized calcium binding adaptor molecule 1 （Iba1）， interleukin-1β （IL-1β）， and IL-18 in hippocampal tissues were detected. The protein expressions of NLRP3， cluster of differentiation 68 （CD68）， Caspase-1， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein were determined， and neuronal apoptosis was observed. RESULTS After the last administration， compared with the model group， the open-field activity time was significantly prolonged （ P ＜0.05）， and the latency to feed in a novel environment was significantly shortened （ P ＜0.05） in rats of the high-dose WYJYG group. In hippocampal tissue， the contents of ASC， Iba1， IL-1β， and IL-18， as well as the protein expression levels of NLRP3， Caspase-1， and CD68， and the positive rate of neuronal apoptosis were all significantly decreased/downregulated （ P ＜0.05）. Bcl-2 protein expression was significantly upregulated （ P ＜0.05）， and the density of neuronal apoptosis-positive cells was significantly reduced （ P ＜0.05）. CONCLUSIONS WYJYG play on antidepressant role by inhibiting the NLRP3/ASC/Caspase-1 pathway， reducing microglia-mediated neuroinflammation， and inhibiting hippocampal neurons apoptosis.

Objective:To explore the predictive value of preoperative peripheral hematological parameters combined with clinicopathological features for cervical lymph node metastasis（CLNM） in patients with laryngeal squamous cell carcinoma（LSCC）, and to construct and validate a nomogram model for CLNM. Methods:A retrospective analysis was conducted on the clinical data of 264 LSCC patients who underwent surgical treatment and were pathologically confirmed, collected from the Second Affiliated Hospital of Shandong First Medical University and Taian 88 Hospital. Specifically, 161 patients from one hospital were allocated to the training cohort, while 103 patients from another hospital constituted the validation cohort. Based on postoperative pathological results, patients were categorized into CLNM-positive and CLNM-negative groups. The general clinical data, clinicopathological features, and hematological parameters of the two groups were analyzed and compared. A preoperative predictive model for CLNM was developed using logistic regression analysis, followed by validation and sensitivity analysis to evaluate the robustness of the model's predictive performance. Results:The results showed that there were significant differences in tumor location, tumor size, tumor differentiation, neutrophil percentage, lymphocyte count, lymphocyte percentage, c-reactive protein（CRP）, fibrinogen, neutrophil-to-lymphocyte ratio（NLR）, platelet-to-lymphocyte ratio（PLR）, systemic immune-inflammation index（SII）, systemic inflammation response index（SIRI）, and prognostic inflammatory index（PIV） between the CLNM-positive and CLNM-negative groups（P<0.05）. Lasso regression identified tumor location, clinical T stage, tumor size, tumor differentiation degree, red blood cell distribution width（RDW） -coefficient of variation（RDW-CV）, CRP, FIB, D-dimer, NLR, and lymphocyte-to-monocyte ratio（LMR） were the most predictive parameters. Multivariate logistic regression revealed that tumor location, tumor size, tumor differentiation degree, CRP, and NLR were independent risk factors for CLNM in LSCC patients（P<0.05）. A nomogram was constructed based on these five factors. The model demonstrated excellent discrimination, with a C-index of 0.837（95%CI 0.766-0.908） in the training cohort and 0.809（95%CI 0.698-0.920） in the validation cohort. Calibration curves and DCA curves in both cohorts confirmed the clinical utility of the model. Sensitivity analysis further supported the robustness of the results, showing good discrimination and calibration across different age and BMI subgroups. Conclusion:Tumor location, tumor size, tumor differentiation degree, CRP, and NLR were independent risk factors for CLNM in LSCC patients. The nomogram based on these variables exhibits strong discrimination, calibration, and clinical applicability, and may serve as a valuable tool for preoperative risk assessment and individualized treatment planning.
Humans ; Nomograms ; Laryngeal Neoplasms/blood* ; Retrospective Studies ; Lymphatic Metastasis ; Carcinoma, Squamous Cell/blood* ; Lymph Nodes/pathology* ; Male ; Female ; Middle Aged ; Neck ; C-Reactive Protein ; Aged ; Logistic Models ; Neutrophils ; Prognosis

Background/Aims: Extended hepatectomy combined with caudate lobe resection has been approved for the radical resection of hilar cholangiocarcinoma. There was a lack of credible research on the clinical value of caudate lobectomy (CL) for intrahepatic cholangiocarcinoma involving the hepatic hilus when combined with hepatectomy. We aimed to compare the short-term and long-term outcomes of the combined procedure with those of only CL for curative resection of intrahepatic cholangiocarcinoma involving the hepatic hilus. Methods: This single-center retrospective cohort study of patients with hilar cholangiocarcinoma was conducted from January 2007 to December 2021. Patients who underwent radical resection were enrolled in this study. The short-term and long-term clinical outcomes of the groups were compared before and after propensity score matching (PSM). Results: A total of 282 patients were included. There were no statistically significant differences in perioperative clinical outcomes between the CL group and the non-CL group before and after PSM. Compared to patients in the non-CL group, patients in the CL group had significantly longer overall survival before and after PSM (p=0.007 before PSM, p=0.033 after PSM). Moreover, compared to the non-CL group, the CL group had longer disease-free survival before and after PSM (p<0.001 before PSM, p=0.019 after PSM). Conclusions The postoperative complications of the CL group were comparable to those of the non-CL group. CL improved the long-term survival of patients with intrahepatic cholangiocarcinoma involving the hepatic hilus when combined with hepatectomy. Therefore, hepatectomy combined with caudate lobe resection should be performed for patients with hilar cholangiocarcinoma.

Background/Aims: Extended hepatectomy combined with caudate lobe resection has been approved for the radical resection of hilar cholangiocarcinoma. There was a lack of credible research on the clinical value of caudate lobectomy (CL) for intrahepatic cholangiocarcinoma involving the hepatic hilus when combined with hepatectomy. We aimed to compare the short-term and long-term outcomes of the combined procedure with those of only CL for curative resection of intrahepatic cholangiocarcinoma involving the hepatic hilus. Methods: This single-center retrospective cohort study of patients with hilar cholangiocarcinoma was conducted from January 2007 to December 2021. Patients who underwent radical resection were enrolled in this study. The short-term and long-term clinical outcomes of the groups were compared before and after propensity score matching (PSM). Results: A total of 282 patients were included. There were no statistically significant differences in perioperative clinical outcomes between the CL group and the non-CL group before and after PSM. Compared to patients in the non-CL group, patients in the CL group had significantly longer overall survival before and after PSM (p=0.007 before PSM, p=0.033 after PSM). Moreover, compared to the non-CL group, the CL group had longer disease-free survival before and after PSM (p<0.001 before PSM, p=0.019 after PSM). Conclusions The postoperative complications of the CL group were comparable to those of the non-CL group. CL improved the long-term survival of patients with intrahepatic cholangiocarcinoma involving the hepatic hilus when combined with hepatectomy. Therefore, hepatectomy combined with caudate lobe resection should be performed for patients with hilar cholangiocarcinoma.

Background/Aims: Extended hepatectomy combined with caudate lobe resection has been approved for the radical resection of hilar cholangiocarcinoma. There was a lack of credible research on the clinical value of caudate lobectomy (CL) for intrahepatic cholangiocarcinoma involving the hepatic hilus when combined with hepatectomy. We aimed to compare the short-term and long-term outcomes of the combined procedure with those of only CL for curative resection of intrahepatic cholangiocarcinoma involving the hepatic hilus. Methods: This single-center retrospective cohort study of patients with hilar cholangiocarcinoma was conducted from January 2007 to December 2021. Patients who underwent radical resection were enrolled in this study. The short-term and long-term clinical outcomes of the groups were compared before and after propensity score matching (PSM). Results: A total of 282 patients were included. There were no statistically significant differences in perioperative clinical outcomes between the CL group and the non-CL group before and after PSM. Compared to patients in the non-CL group, patients in the CL group had significantly longer overall survival before and after PSM (p=0.007 before PSM, p=0.033 after PSM). Moreover, compared to the non-CL group, the CL group had longer disease-free survival before and after PSM (p<0.001 before PSM, p=0.019 after PSM). Conclusions The postoperative complications of the CL group were comparable to those of the non-CL group. CL improved the long-term survival of patients with intrahepatic cholangiocarcinoma involving the hepatic hilus when combined with hepatectomy. Therefore, hepatectomy combined with caudate lobe resection should be performed for patients with hilar cholangiocarcinoma.

Background/Aims: Extended hepatectomy combined with caudate lobe resection has been approved for the radical resection of hilar cholangiocarcinoma. There was a lack of credible research on the clinical value of caudate lobectomy (CL) for intrahepatic cholangiocarcinoma involving the hepatic hilus when combined with hepatectomy. We aimed to compare the short-term and long-term outcomes of the combined procedure with those of only CL for curative resection of intrahepatic cholangiocarcinoma involving the hepatic hilus. Methods: This single-center retrospective cohort study of patients with hilar cholangiocarcinoma was conducted from January 2007 to December 2021. Patients who underwent radical resection were enrolled in this study. The short-term and long-term clinical outcomes of the groups were compared before and after propensity score matching (PSM). Results: A total of 282 patients were included. There were no statistically significant differences in perioperative clinical outcomes between the CL group and the non-CL group before and after PSM. Compared to patients in the non-CL group, patients in the CL group had significantly longer overall survival before and after PSM (p=0.007 before PSM, p=0.033 after PSM). Moreover, compared to the non-CL group, the CL group had longer disease-free survival before and after PSM (p<0.001 before PSM, p=0.019 after PSM). Conclusions The postoperative complications of the CL group were comparable to those of the non-CL group. CL improved the long-term survival of patients with intrahepatic cholangiocarcinoma involving the hepatic hilus when combined with hepatectomy. Therefore, hepatectomy combined with caudate lobe resection should be performed for patients with hilar cholangiocarcinoma.

Objective To investigate the impact of mitophagy,mediated by the long non-coding RNA SNHG16(LncRNA SNHG16)on diabetes-associated cognitive impairment(DCI).Methods 29 male C57BL/J mice were randomly divided into normal control(NC)group,DCI group and DCI+mitochondrial autophagy inhibitor(DCI+Mdivi-1)group.Morris water maze and new object recognition test were used to detect the cognitive function of mice,qRT-CPR was used to detect the expression of LncRNA SNHG16 and mitochondrial autophagy marker mRNA.Western blot were used to detect the expression of related protein.The mouse hippocampal neurons HT22 were divided into control(Con)group,high glucose(HG)group,HG+SNHG16 silencing(HG+sh-SNHG16)group and HG+no-load control(HG+sh-NC)group.CCK8 method and lactate dehydrogenase(LDH)method were used to detect neuronal damage.JC-1 method was used to detect mitochondrial membrane potential.Results Compared with NC group,the expression of LncRNA SNHG16 and the expression of autophagy-related gene 5,PTEN-induced putative kinase 1(PINK1),Parkin and microtubule associated protein light chain 3(LC3)Ⅱ/Ⅰ increased(P<0.05),while the expression of mitochondrial autophagy-related proteins P62 and mitochondrial outer membrane transposase 20(TOMM20)decreased in T2DM group.Compared with DCI group,the cognitive dysfunction of mice improved,and the expression level of LncRNA SNHG16 decreased in the DCI+Mdivi-1 group(P<0.05).The expressions of LncRNA SNHG16,LC3 Ⅱ/Ⅰ,PINK1 and Parkin were higher in HG group than in Con group(P<0.05),while the cell survival rate and TOMM20 protein expression were lower in HG group than in Con group(P<0.05).Silence of LncRNA SNHG16 can restore the activity of HT22 cells and mitochondrial membrane potential,and reduce the level of mitochondrial autophagy under HG condition.Conclusions The expression level of LncRNA SNHG16 was up-regulated in the hippocampus brain region of mice with diabetic cognitive dysfunction,and mitophagy was overactivated.Silencing of LncRNA SNHG16 inhibits mitophagy in hippocampal neurons and alleviates HG induced hippocampal neuronal damage.

Objective To investigate the impact of mitophagy,mediated by the long non-coding RNA SNHG16(LncRNA SNHG16)on diabetes-associated cognitive impairment(DCI).Methods 29 male C57BL/J mice were randomly divided into normal control(NC)group,DCI group and DCI+mitochondrial autophagy inhibitor(DCI+Mdivi-1)group.Morris water maze and new object recognition test were used to detect the cognitive function of mice,qRT-CPR was used to detect the expression of LncRNA SNHG16 and mitochondrial autophagy marker mRNA.Western blot were used to detect the expression of related protein.The mouse hippocampal neurons HT22 were divided into control(Con)group,high glucose(HG)group,HG+SNHG16 silencing(HG+sh-SNHG16)group and HG+no-load control(HG+sh-NC)group.CCK8 method and lactate dehydrogenase(LDH)method were used to detect neuronal damage.JC-1 method was used to detect mitochondrial membrane potential.Results Compared with NC group,the expression of LncRNA SNHG16 and the expression of autophagy-related gene 5,PTEN-induced putative kinase 1(PINK1),Parkin and microtubule associated protein light chain 3(LC3)Ⅱ/Ⅰ increased(P<0.05),while the expression of mitochondrial autophagy-related proteins P62 and mitochondrial outer membrane transposase 20(TOMM20)decreased in T2DM group.Compared with DCI group,the cognitive dysfunction of mice improved,and the expression level of LncRNA SNHG16 decreased in the DCI+Mdivi-1 group(P<0.05).The expressions of LncRNA SNHG16,LC3 Ⅱ/Ⅰ,PINK1 and Parkin were higher in HG group than in Con group(P<0.05),while the cell survival rate and TOMM20 protein expression were lower in HG group than in Con group(P<0.05).Silence of LncRNA SNHG16 can restore the activity of HT22 cells and mitochondrial membrane potential,and reduce the level of mitochondrial autophagy under HG condition.Conclusions The expression level of LncRNA SNHG16 was up-regulated in the hippocampus brain region of mice with diabetic cognitive dysfunction,and mitophagy was overactivated.Silencing of LncRNA SNHG16 inhibits mitophagy in hippocampal neurons and alleviates HG induced hippocampal neuronal damage.

Objective:To investigate the mechanisms underlying the effect of levocarnitine on myocardial cell fibrosis, proliferation, apoptosis and migration.Methods:Between June and December 2022, an overexpression vector for tissue inhibitor-1 of metalloproteinase(TIMP-1)and siRNA TIMP-1 were used to transfect rat H9c2 cardiomyocytes(from the cell bank of the Chinese Academy of Sciences), and transfection efficiency was measured using fluorescence reverse transcription quantitative PCR(RT-qPCR). After treating H9c2 cells with angiotensin Ⅱ(AngⅡ), the expression of the MMP3 and TIMP-1 genes in the cells was detected by RT-qPCR.A CCK8 kit was used to assess the effect of levocarnitine intervention on the proliferation of myofibroblasts after overexpression or knockdown of TIMP-1.The effects of levocarnitine on apoptosis and migration of myofibroblasts were detected by flow cytometry and Transwell assays.Results:The RT-qPCR results showed that the expression level of the MMP3 gene(1.38±0.05)in cardiomyocytes treated with AngⅡ for 24 hours exhibited an upward trend( P<0.01), while the expression level of the TIMP-1 gene(0.71±0.03)showed a downward trend( P<0.01). In addition, H9c2 cells with TIMP-1 overexpression(905.98±24.17)and knockdown(0.18±0.01)%, respectively, were successfully constructed.Based on CCK-8 detection results, knockdown of TIMP-1(86.56±7.98)% was able to promote the proliferation of H9c2 cells induced by levocarnitine( P<0.01). Apoptosis experiments showed that inhibition of TIMP-1 expression(23.22±2.69)significantly reduced the apoptosis level of H9c2 cells induced by levocarnitine( P<0.01). Migration experiments showed that inhibition of TIMP-1 expression(217.67±23.44)significantly promoted the migration ability of H9c2 cells induced by levocarnitine( P<0.01). Conclusions:After intervention to reduce TIMP-1 expression, levocarnitine can promote proliferation, inhibit apoptosis and promote migration of myofibroblasts and may therefore ameliorate myocardial fibrosis.

Objective:To analyze the level and clinical significance of IL-18 and IL-18-binding protein (BP) in the bone marrow of patients with myelodysplastic syndrome (MDS) .Methods:A total of 43 newly diagnosed patients with MDS who were admitted to the Department of Hematology, Tianjin Medical University General Hospital, from July 2020 to February 2021 were randomly selected. The control group consisted of 14 patients with acute myeloid leukemia (AML) and 25 patients with iron-deficiency anemia (IDA). The levels of IL-18 and IL-18 BP in the bone marrow supernatant were measured, and their correlations with MDS severity, as well as the functionality of CD8 + T cells and natural killer cells, was analyzed. Results:The levels of IL-18, IL-18 BP, and free IL-18 (fIL-18) in the bone marrow supernatant of patients with MDS were higher than in the IDA group. The level of fIL-18 was linearly and negatively correlated with the MDS-International Prognostic Scoring System (IPSS) score. IL-18 receptor (IL-18Rα) expression on CD8 + T cells in the MDS group was lower than in the IDA group, and the levels of fIL-18 and IL-18Rα were positively correlated with CD8 + T-cell function in the MDS group. Conclusion:IL-18 BP antagonizes IL-18, leading to a decrease in fIL-18 in the bone marrow microenvironment of patients with MDS, affecting CD8 + T-cell function, which is closely related to MDS severity; therefore, it may become a new target for MDS treatment.