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.

BACKGROUND:Previous studies have found that neohesperidin can delay bone loss in ovariectomized mice and has the potential to treat osteoporosis,but its specific mechanism of action remains to be explored. OBJECTIVE:To explore the key targets and possible mechanisms of neohesperidin in the treatment of osteoporosis based on bioinformatics and cell experiments in vitro. METHODS:The gene expression dataset related to osteoporosis was obtained from GEO database,and the differentially expressed genes were screened and analyzed in R language.The osteoporosis-related targets were screened from GeneCards and DisGeNET databases,and the neohesperidin-related targets were screened from ChEMBL and PubChem databases,and the common targets were obtained by intersection of the three.The String database was used to construct the PPI network of intersection genes,and the key targets were screened.The DAVID database was used for GO and KEGG enrichment analysis.The AutoDock software was used to verify the molecular docking between the neohesperidin and the target protein.The effect of neohesperidin on osteogenic differentiation of C57 mouse bone marrow mesenchymal stem cells was detected.Complete medium was used as blank control group;osteogenic induction medium was used as the control group;and osteogenic induction medium containing different concentrations of neohesperidin(25,50 μmol/L)was used as experimental group.The expression of alkaline phosphatase,the degree of mineralization,the expression of osteogenic-related genes and target genes during osteogenic differentiation of cells were measured at corresponding time points. RESULTS AND CONCLUSION:(1)9 253 differentially expressed genes,2 161 osteoporosis-related targets,and 326 neohesperidin-related targets were screened.There were 53 common targets among the three.All 53 genes were up-regulated in osteoporosis samples.The PPI network screened the target gene PRKACA of research significance.GO function and KEGG pathway enrichment analysis showed that neohesperidin's treatment of osteoporosis through PRKACA target mainly depended on biological processes such as protein phosphorylation and protein autophosphorylation,acting on endocrine resistance,proteoglycan in cancer,and estrogen signaling pathway to play a therapeutic role.Molecular docking results showed that neohesperidin had a certain binding ability to the protein corresponding to the target PRKACA.(2)The results of alkaline phosphatase staining showed that neohesperidin could promote the expression of alkaline phosphatase in the early stage of osteogenic differentiation of mesenchymal stem cells.Alizarin red staining showed that neohesperidin could promote the mineralization of osteogenic differentiation of mesenchymal stem cells.RT-qPCR results showed that neohesperidin could increase the mRNA expression of alkaline phosphatase,PRKACA,and osteocalcin.(3)These results indicate that neohesperidin may promote osteogenic differentiation through PRKACA target on the estrogen signaling pathway to prevent and treat osteoporosis.

Tumor budding is a distinct pathomorphological feature observed in various types of solid tumor.In recent years,tumor budding has been recognized as an important biological feature associated with tumor invasion and metastasis,and it has become a new focus in the research on tumor progression.Although studies have explored the role of tumor budding in different types of tumor,there are studies in the field of hepatocellular carcinoma(HCC).This article systematically reviews the research advances in tumor budding in HCC,with a focus on the mechanism of tumor budding,the association between tumor budding and tumor progression,and the potential application of tumor budding in prognostic assessment,in order to provide new insights and strategies for the early diagnosis and treatment of HCC.

OBJECTIVES: In the early stage of central cervical disc herniation, clinical symptoms may be mild. However, as the spinal cord becomes compressed by herniated nucleus pulposus tissue, progressive edema and degeneration may occur, resulting in more severe clinical manifestations, including limb weakness, bladder and bowel dysfunction, spastic paraplegia of the lower extremities, and even respiratory difficulty. The spinal endoscopic Key-hole technique is widely applied in treating radiculopathic cervical spondylosis and has demonstrated good clinical outcomes. This study aims to analyze and summarize the technical points and therapeutic efficacy of the far lateral Key-hole technique in the treatment of central cervical disc herniation, providing reference for clinical application. METHODS: Eight patients with central cervical disc herniation treated with the far lateral Key-hole technique were included as the experimental group. Another 8 patients who underwent single-level anterior cervical diskectomy and fusion (ACDF) during the same period were selected as the control group. Data collected included gender, age, intraoperative blood loss, incision length, and length of hospitalization. Pain severity was evaluated using the Visual Analogue Scale (VAS); cervical function was assessed using the Japanese Orthopaedic Association (JOA) score; and cervical disability was measured by the neck disability index (NDI). Radiological outcomes were assessed using disc height index (DHI), cervical Cobb angle, and operative segment Cobb angle. RESULTS: Compared with the control group, the experimental group had significantly less intraoperative blood loss, shorter incision length, and shorter hospital stay (all P<0.05), while there was no significant difference in operation time (P>0.05). Postoperative VAS and NDI scores in both groups were significantly lower than preoperative values, and JOA scores significantly improved (P<0.05). No significant differences were noted between the two groups preoperatively (P>0.05). Postoperatively, the experimental group showed significantly lower VAS and NDI scores and higher JOA scores than the control group (P<0.05). There was no statistical significance in DHI before and after surgery in the experimental group (P>0.05), while the DHI increased significantly postoperatively in the control group (P<0.05). Postoperative DHI in the experimental group was significantly lower than in the control group (P<0.05). No significant differences were observed in the cervical Cobb angle either within or between groups (all P>0.05). The operative segment Cobb angle increased significantly after surgery in the control group (P<0.05), while no other operative segment angle changes were statistically significant (all P>0.05). CONCLUSIONS The far lateral Key-hole technique offers advantages in treating central cervical disc herniation, including reduced intraoperative bleeding, smaller incision length, shorter hospitalization, and improved postoperative pain relief. Additionally, the technique does not affect cervical physiological curvature or stability in the short term, making it suitable for clinical application.
Humans ; Intervertebral Disc Displacement/surgery* ; Cervical Vertebrae/surgery* ; Male ; Female ; Middle Aged ; Adult ; Diskectomy/methods* ; Treatment Outcome ; Spinal Fusion/methods* ; Endoscopy/methods*

Objective To identify the factors influencing postoperative recurrence in endometriosis patients after laparoscopic surgery and to evaluate their clinical predictive performance for postoperative recurrence.Methods The clinical data of 190 endometriosis patients who underwent laparoscopic surgery at our hospital between January 2019 and January 2024 were retrospectively collected.Patients were divided into a non-recurrence group(109 cases)and a recurrence group(81 cases)based on their status of postoperative recurrence.Univariate analysis was performed with the clinical data.Multivariate logistic regression analysis was performed to identify the influencing factors of recurrence after laparoscopic surgery.Receiver operating characteristic(ROC)curve analysis was used to evaluate the predictive value of the relevant indicators.Results According to the results of the univariate analysis,the prevalence of preoperative history of dysmenorrhea,number of preoperative pregnancies,history of previous uterine cavity procedures,smoking,and drinking in the non-recurrence group was lower than that in the recurrence group(P<0.05).The non-recurrence group also had lower preoperative serum levels of transforming growth factor-β1(TGF-β1),interleukin(IL)-1β,IL-17,and IL-22 compared with those of the recurrence group(P<0.05).Except for the history of previous uterine cavity procedures,drinking,and the level of IL-17,all other factors were independent risk factors for recurrence after laparoscopic surgery(P<0.05).The area under the curve(AUC)for preoperative serum TGF-β1+IL-1β and TGF-β1+IL-1β+IL-22 was 0.980(95%CI,0.965-0.994)and 0.982(95%CI,0.968-0.996),respectively,indicating a high predictive value for recurrence in patients after laparoscopic surgery.Conclusion The history of preoperative dysmenorrhea,number of preoperative pregnancies,smoking,and preoperative levels of serum TGF-β1,IL-1β,and IL-22 are risk factors for the recurrence of endometriosis after laparoscopic surgery.The combination of TGF-β1 and IL-1β,as well as the combination of TGF-β1,IL-1β,and IL-22,both demonstrated good performance for predicting the recurrence of endometriosis after laparoscopic surgery.

Tumor budding is a distinct pathomorphological feature observed in various types of solid tumor. In recent years， tumor budding has been recognized as an important biological feature associated with tumor invasion and metastasis， and it has become a new focus in the research on tumor progression. Although studies have explored the role of tumor budding in different types of tumor， there are studies in the field of hepatocellular carcinoma （HCC）. This article systematically reviews the research advances in tumor budding in HCC， with a focus on the mechanism of tumor budding， the association between tumor budding and tumor progression， and the potential application of tumor budding in prognostic assessment， in order to provide new insights and strategies for the early diagnosis and treatment of HCC.

Purpose This study aimed to evaluate the consistency of human epidermal growth factor receptor 2(HER2)status between primary breast cancer lesions and lung metastatic lesions and to establish a prognostic model for predicting the survival rate of HER2 low expression(HER2-low)breast cancer patients with lung metastasis.Methods Clinicopathological data from a cohort of 252 patients with breast cancer and lung metastasis were retrospec-tively analyzed.Results 50.00％of the patients had HER2-low expression in metastatic lesions,and HER2-low ex-pression was the most prevalent subgroup in both primary and metastatic lesions.A discordance in HER2 status be-tween primary and metastatic sites was observed in 28.07％of cases.The most frequent shift was from HER2-zero in the primary tumor to HER2-low expression in the metastasis(12.28％of all cases).Estrogen receptor(ER)status,menopausal status,and histological type were identified as independent prognostic factors for overall survival(OS)by univariate and multivariate Cox regression analyses.A prognostic model incorporating these factors was constructed to predict 3-year and 5-year survival.The model demonstrated area under the curve(AUC)values of 0.765 and 0.780 for 3-year and 5-year OS in the training cohort,and 0.667 and 0.706 in the validation cohort,respectively.Conclu-sion HER2-low expression is the most common subtype among breast cancer patients with lung metastasis.The ob-served shift from HER2-zero in primary lesions to HER2-low in metastases underscores the clinical necessity of re-biop-sy at metastatic sites.The developed prognostic model effectively predicts OS in this patient population.

BACKGROUND:A large number of studies have confirmed that both amniotic extracellular matrix materials and bladder extracellular matrix materials can be used as stem cell carriers for the treatment of endometrial injury,but the difference in effect between the two materials is relatively rare.OBJECTIVE:To compare the difference of amniotic extracellular matrix materials and bladder extracellular matrix materials as stem cell carrier in the treatment of endometrial injury.METHODS:Whole bone marrow adhesion method was used to isolate and purify bone marrow mesenchymal stem cells from SD rats.SD-rat amniotic extracellular matrix materials and bladder extracellular matrix materials were prepared respectively,and then bone marrow mesenchymal stem cells were inoculated on the surface of the two materials to detect cell proliferation and adhesion.Forty SD rats were randomly divided into four groups(n=10 per group).Except the sham operation group,the endometrial injury group,the amniotic extracellular matrix group,and the bladder extracellular matrix group were all established by mechanical intervention.The amniotic extracellular matrix/bone marrow mesenchymal stem cell complex and bladder stromal extracellular matrix/bone marrow mesenchymal stem cell complex were transplanted into the injured endometrial site in the amniotic extracellular matrix group and the bladder extracellular matrix group.Samples were collected and detected 14 and 28 days after transplantation.The morphology of rat endometrial tissue was observed by hematoxylin-eosin staining.The levels of basic fibroblast growth factor,insulin-like growth factor 1,and vascular endothelial growth factor in endometrial tissues were analyzed by enzyme-linked immunosorbent assay.The expression levels of vimentin and CD34 in endometrial tissues were analyzed by immunohistochemical staining.RESULTS AND CONCLUSION:(1)Both kinds of extracellular matrix materials were beneficial to the proliferation of bone marrow mesenchymal stem cells.Compared with bladder extracellular matrix materials,amniotic extracellular matrix materials could promote the adhesion of bone marrow mesenchymal stem cells.(2)Compared with the sham operation group,the levels of basic fibroblast growth factor,insulin-like growth factor 1,and vascular endothelial growth factor were significantly decreased(P<0.01),endometrial tissue was dysplastic,endometrial thickness and number of glands were significantly decreased,and vimentin and CD34 positive expression levels were significantly decreased(P<0.01)in the endometrial injury group.Compared with the endometrial injury group,the levels of basic fibroblast growth factor,insulin-like growth factor 1,and vascular endothelial growth factor were increased(P<0.05 or P<0.01),the endometrial tissue morphology was significantly improved,and the endometrial thickness and the number of glands were significantly increased;the positive expressions of vimentin and CD34 were significantly increased(P<0.05 or P<0.01)in the amniotic extracellular matrix group and the bladder extracellular matrix group,and the improvement of amniotic extracellular matrix group was better than that of bladder extracellular matrix group(P<0.05).(3)The results show that compared with bladder extracellular matrix materials,amniotic extracellular matrix material as a carrier of bone marrow mesenchymal stem cells can further promote the repair of damaged endometrium.

Objective To quantitatively measure the liver fat content and liver fibrosis degree in patients with type 2 diabetes mellitus(T2DM)using liver transient elastography(FibroScan)and analyze the risk factors for metabolism-related fatty liver disease(MAFLD).Methods A retrospective analysis was conducted on the clinical data of 258 patients with T2DM admitted to The Department of Endocrinology,Harbin First Hospital from August 2017 to November 2020.The patients were divided into the simple T2DM group(n=41)and the MAFLD(n=217)group based on whether they had MAFLD.Both groups were assessed using the FibroScan 502 system to measure liver fat content(CAP)and liver fibrosis degree(LSM).General information,TC,TG,LDL-C,HDL-C,FPG,HbA1c,FC-P,FIns,and liver function(AST,ALT,GGT)were compared between the two groups.Results BMI,TG,FC-P,FIns,AST,CAP,and LSM were significantly higher in the MAFLD group than in the simple T2DM group(P<0.05).Pearson phase analysis showed that the DM duration,TG,FC-P and LSM were positively correlated with CAP(P<0.05),while TG,AST and CAP were positively correlated with LSM(P<0.05).Logistic regression analysis revealed that BMI,TG,FC-P,CAP,and LSM were risk factors for T2DM combined with MAFLD.Conclusions Elevated BMI,TG,FC-P,CAP,and LSM are risk factors for the onset of T2DM combined with MAFLD.Additionally,TG is a common factor for the increase in CAP and LSM.FibroScan measurement of CAP and LSM values can quantitatively reveal the liver lesion status in patients with T2DM.

Purpose This study aimed to evaluate the consistency of human epidermal growth factor receptor 2(HER2)status between primary breast cancer lesions and lung metastatic lesions and to establish a prognostic model for predicting the survival rate of HER2 low expression(HER2-low)breast cancer patients with lung metastasis.Methods Clinicopathological data from a cohort of 252 patients with breast cancer and lung metastasis were retrospec-tively analyzed.Results 50.00％of the patients had HER2-low expression in metastatic lesions,and HER2-low ex-pression was the most prevalent subgroup in both primary and metastatic lesions.A discordance in HER2 status be-tween primary and metastatic sites was observed in 28.07％of cases.The most frequent shift was from HER2-zero in the primary tumor to HER2-low expression in the metastasis(12.28％of all cases).Estrogen receptor(ER)status,menopausal status,and histological type were identified as independent prognostic factors for overall survival(OS)by univariate and multivariate Cox regression analyses.A prognostic model incorporating these factors was constructed to predict 3-year and 5-year survival.The model demonstrated area under the curve(AUC)values of 0.765 and 0.780 for 3-year and 5-year OS in the training cohort,and 0.667 and 0.706 in the validation cohort,respectively.Conclu-sion HER2-low expression is the most common subtype among breast cancer patients with lung metastasis.The ob-served shift from HER2-zero in primary lesions to HER2-low in metastases underscores the clinical necessity of re-biop-sy at metastatic sites.The developed prognostic model effectively predicts OS in this patient population.