Aryl hydrocarbon receptor （AhR） plays an important role in the development and progression of liver diseases. This article elaborates on the structure of AhR and its function in liver development and provides a detailed analysis of its molecular mechanisms in diseases such as metabolic associated fatty liver disease， alcoholic liver disease， viral hepatitis， drug-induced liver injury， autoimmune hepatitis， liver cirrhosis， and liver cancer. This article also reviews the research advances in AhR agonists and antagonists and analyzes their potential application prospects in disease treatment. At the same time， it points out that although AhR is a promising therapeutic target， there are still various challenges in its clinical application. It is suggested that future research should focus on developing AhR modulators with high specificity and low toxicity and further explore its mechanism of action in different liver diseases.

Objective:This study aims to investigate the behavioral changes, gut microbiota alterations, and short-chain fatty acid levels in mice with chronic dizocilpine (MK-801) administration and to evaluate the correlation between gut microbiota and its metabolites with schizophrenia-like behaviors.Methods:This study was conducted from March to September 2024, involving 24 male C57BL/6 mice aged 6 to 8 weeks, purchased from the Guangdong Provincial Medical Laboratory Animal Center. The mice were randomly divided into a control group and a model group using a random number table method. The model group mice were intraperitoneally injected with MK-801 (0.6 mg/kg) for 14 days, while the control group mice were intraperitoneally injected with an equal amount of normal saline for 14 days. After modeling, behavioral performance was assessed using the open field test (OFT), novel object recognition test (NOR), forced swimming test (FST), tail suspension test (TST), elevated plus maze test (EPM), and prepulse inhibition test (PPI). Additionally, mouse feces were collected for 16S rRNA sequencing to analyze the composition of gut microbiota. The gas chromatography-tandem mass spectrometry (GC-MS/MS) was applied to detect the levels of short-chain fatty acids quantitatively. Between-group comparisons of behavioral data were performed using an independent samples t-test or repeated measures ANOVA with adjusted Bonferroni or corrected Greenhouse-Geisser. Between-group comparisons of gut microbiota composition were conducted using an independent samples t-test or the Mann-Whitney U test. Between-group comparisons of short-chain fatty acids were performed using an independent samples t-test. The correlations among behavioral indicators, gut microbiota composition, and short-chain fatty acids were analyzed using Spearman′s rank correlation. Results:(1) Behavioral experiments showed that the model group mice exhibited significantly prolonged immobility times in the FST and TST ( t=-4.84, -2.54; P<0.05), significantly reduced exploration frequency and time in the open arms of the EPM ( t=3.31, 2.48; P<0.05), significantly lower PPI at 76 dB, 79 dB, and 85 dB ( F=23.28, 10.65, 17.82; P<0.05), and a significantly reduced NOR index ( t=2.90, P<0.05) compared to the control group, indicating successful modeling. (2)16S rRNA sequencing revealed that, compared with the control group, the model group exhibited significantly lower relative abundances of Actinobacteriota, Coriobacteriia, Coriobacteriales, and Ileibacterium( Z=-3.10--2.04, all P<0.05). Conversely, the relative abundances of Tannerellaceae, Rikenellaceae, Alistipes, Bacteroides, Intestinimonas, Parabacteroides, Unclassified_f_Prevotellaceae, and unclassified_f_Erysipelotrichaceae significantly increased ( Z=-3.78--2.04; all P<0.05). (3)GC-MS/MS analysis showed that the concentrations of acetic acid and butyric acid in the feces of the model group were significantly lower compared to the control group ( t=2.66, 2.10; P<0.05). (4)Spearman correlation analysis with FDR correction (Benjamini-Hochberg method) revealed that Actinobacteriota significantly positively correlated with the open-arm exploration frequency in the EPM ( r=0.69, Q<0.05), whereas unclassified_f_Erysipelotrichaceae significantly negatively correlated with this measure ( r=-0.66, Q<0.05). Additionally, Bacteroides and Intestinimonas were significantly negatively correlated with PPI at 85 dB ( r=-0.71, -0.63; Q<0.05).Conversely, Ileibacterium demonstrated a significant positive correlation with PPI at 85 dB ( r=0.64, Q<0.05). Conclusion:Alterations in gut microbiota and SCAFs may be associated with MK-801-induced schizophrenia-like behaviors.

Objective:This study aims to investigate the behavioral changes, gut microbiota alterations, and short-chain fatty acid levels in mice with chronic dizocilpine (MK-801) administration and to evaluate the correlation between gut microbiota and its metabolites with schizophrenia-like behaviors.Methods:This study was conducted from March to September 2024, involving 24 male C57BL/6 mice aged 6 to 8 weeks, purchased from the Guangdong Provincial Medical Laboratory Animal Center. The mice were randomly divided into a control group and a model group using a random number table method. The model group mice were intraperitoneally injected with MK-801 (0.6 mg/kg) for 14 days, while the control group mice were intraperitoneally injected with an equal amount of normal saline for 14 days. After modeling, behavioral performance was assessed using the open field test (OFT), novel object recognition test (NOR), forced swimming test (FST), tail suspension test (TST), elevated plus maze test (EPM), and prepulse inhibition test (PPI). Additionally, mouse feces were collected for 16S rRNA sequencing to analyze the composition of gut microbiota. The gas chromatography-tandem mass spectrometry (GC-MS/MS) was applied to detect the levels of short-chain fatty acids quantitatively. Between-group comparisons of behavioral data were performed using an independent samples t-test or repeated measures ANOVA with adjusted Bonferroni or corrected Greenhouse-Geisser. Between-group comparisons of gut microbiota composition were conducted using an independent samples t-test or the Mann-Whitney U test. Between-group comparisons of short-chain fatty acids were performed using an independent samples t-test. The correlations among behavioral indicators, gut microbiota composition, and short-chain fatty acids were analyzed using Spearman′s rank correlation. Results:(1) Behavioral experiments showed that the model group mice exhibited significantly prolonged immobility times in the FST and TST ( t=-4.84, -2.54; P<0.05), significantly reduced exploration frequency and time in the open arms of the EPM ( t=3.31, 2.48; P<0.05), significantly lower PPI at 76 dB, 79 dB, and 85 dB ( F=23.28, 10.65, 17.82; P<0.05), and a significantly reduced NOR index ( t=2.90, P<0.05) compared to the control group, indicating successful modeling. (2)16S rRNA sequencing revealed that, compared with the control group, the model group exhibited significantly lower relative abundances of Actinobacteriota, Coriobacteriia, Coriobacteriales, and Ileibacterium( Z=-3.10--2.04, all P<0.05). Conversely, the relative abundances of Tannerellaceae, Rikenellaceae, Alistipes, Bacteroides, Intestinimonas, Parabacteroides, Unclassified_f_Prevotellaceae, and unclassified_f_Erysipelotrichaceae significantly increased ( Z=-3.78--2.04; all P<0.05). (3)GC-MS/MS analysis showed that the concentrations of acetic acid and butyric acid in the feces of the model group were significantly lower compared to the control group ( t=2.66, 2.10; P<0.05). (4)Spearman correlation analysis with FDR correction (Benjamini-Hochberg method) revealed that Actinobacteriota significantly positively correlated with the open-arm exploration frequency in the EPM ( r=0.69, Q<0.05), whereas unclassified_f_Erysipelotrichaceae significantly negatively correlated with this measure ( r=-0.66, Q<0.05). Additionally, Bacteroides and Intestinimonas were significantly negatively correlated with PPI at 85 dB ( r=-0.71, -0.63; Q<0.05).Conversely, Ileibacterium demonstrated a significant positive correlation with PPI at 85 dB ( r=0.64, Q<0.05). Conclusion:Alterations in gut microbiota and SCAFs may be associated with MK-801-induced schizophrenia-like behaviors.

The effect of Radix isatidis polysaccharide(IRPS)on TLR3/TRIF innate immune path-way and type Ⅰ interferon secretion in 3D4/21/CD163 cells infected by porcine reproductive and re-spiratory syndrome virus(PRRSV)was tested by Western blot and ELISA;moreover,the effect of IRPS on the immunosuppression infected by PRRSV was further verified with the TLR3 agonist poly(I∶C).The results showed that the protein levels of TLR3,TRIF,IRF3,IRF7 and type Ⅰ in-terferon secretion were significantly decreased at 18,24 h of PRRSV infection,while IRPS signifi-cantly inhibited this process;poly(I∶C)alleviated the protein levels of TRIF,IRF3 and IRF7 as well as the phosphorylation levels of IRF3 and IRF7 infected by PRRSV;at the same time,IRPS is synergistic with poly(I∶C).The results indicate that IRPS is able to alleviate immunosuppression caused by PRRSV infection via the TLR3/TRIF pathway.

OBJECTIVE To explore the molecular mechanism of urolithin A inhibition of human hepatoma cells growth. METHODS Hepatoma Huh-7 cells were treated with different concentrations of urolithin A(Uro-A). The inhibition rate of Huh-7 cells survival was detected by CCK-8 assay and the IC50 was calculated. Cell proliferation was detected by colony formation assay and cell migration ability was assessed by cell wound healing experiment. Glucose uptake and lactate level in culture medium through colorimetry and the ATP production in cell through chemiluminescence method was analyzed. Western blotting was applied to detect protein expression levels of glucose transporter(GLUT1), key enzymes of glycolysis(HK2, PFKM, LDHA), p53, p-p38 and Bcl-2 after treatment with different concentrations of Uro-A. Flow cytometry and TUNEL method were used to detect apoptosis rate. RESULTS The results of CCK-8 showed that Uro-A significantly inhibited the proliferation of Huh-7 cells, and the IC50 was(48.54±1.21) μmol·L−1. The ability of clone formation and migration decreased after Uro-A treatment. Cellular glucose uptake and level of lactic acid and ATP production were down regulated in Huh-7 cells treated with Uro-A. The results showed that expression of glycolytic key proteins GLUT1, PKM2, LDHA and HK2 decreased. Western Blotting further research indicated that the p53 and p-p38 were activated, while the Bcl-2 was down-regulated. Flow cytometry data and TUNEL method revealed that the induction of apoptosis by Uro-A was remarkably increased. CONCLUSION These findings suggest that Uro-A can suppress Huh-7 cell proliferation and migration. The possible mechanism is the inhibition of glycolysis by p53, p-p38 and Bcl-2, which prevent cell growth and finally induce apoptosis.

Objective To compare the efficacy, safety, and survivability of TCbHP versus AC-THP in the neoadjuvant therapy of HER2-positive breast cancer in real-world. Methods Clinical data of patients with HER2 positive breast cancer, who have received TCbHP or AC-THP as neoadjuvant therapy and completed surgery in 11 third-class hospitals in various cities of Hebei Province, were retrospectively collected.The total pathological complete remission (tpCR) rate, the incidence of grade 3 or higher adverse reactions and the completion rate of the given approaches were compared. Results A total of 110 cases were collected, including 78 cases in the TCbHP group and 32 cases in the AC-THP group.The tpCR rate of the TCbHP group was higher than that of the AC-THP group, but the difference was not statistically significant (64.10% vs. 56.25%, P=0.441).No significant difference was found in the breast pathologic complete response (bpCR) and axillary pathologic complete response (apCR) rates between the TCbHP group and the AC-THP group (70.51% vs. 56.25%, P=0.150;78.21% vs. 84.38%, P=0.462).Exploratory analysis revealed that the tpCR rate of the TCbHP group was significantly higher than that of the AC-THP group in patients with HR-positive breast cancer (51.11% vs. 22.22%, P=0.036).As for the patients with HR-negative breast cancer, the tpCR rate of the AC-THP group tended to be higher than that of the TCbHP group (100% vs. 81.82%, P=0.088).The incidence of grade 3 or higher adverse reactions in the TCbHP group was slightly higher than that in the AC-THP group (12.82% vs. 9.38%, P=0.753).No deaths occurred in the whole group.Moreover, no significant difference was observed in the completion rate of the given approaches between the TCbHP group and the AC-THP group (92.31% vs. 90.63%, P=0.718). Conclusion In real-world clinical practice, the neoadjuvant therapy of TCbHP and AC-THP are effective, safe, and well tolerated among patients with HER2-positive breast cancer.The tpCR rate between the two approaches was not significantly different.The AC-THP regimen could also be considered as one of the optimal regimens for HER2-positive breast cancer in neoadjuvant therapy.

Objective:To compare the clinical value of stent assisted intestinal bypass and temporary loop ileostomy in laparoscopic low anterior resection of rectal cancer.Method:In this retrospective analysis, 57 patients undergoing laparoscopic low anterior resection for rectal cancer in the First Affiliated Hospital of Ningbo University from Jan 2020 to Jan 2022 were divided into intestinal bypass group (36 cases) and loop ileostomy group (21 cases).Result:There were no significant differences in postoperative GI function recovery and postoperative complication rate between the two groups (all P>0.05). The levels of albumin, prealbumin and hemoglobin in the intestinal bypass group were better than those in the ileostomy group when evaluated on 3rd months after operation [(40.5±2.3) g/L vs. (38.1±2.6)g/L、(26.4±2.7)mg/dl vs. (24.5±2.0)mg/dl、(137.6±5.9) g/L vs. (134.0±7.0) g/L, t=3.605、2.743、2.085, all P<0.05]. Hospital expenses of the intestinal bypass group was lower [(571 000±7 500) yuan vs. (69 300±9 100) yuan, t=-5.477, P<0.05]. Conclusion:Compared with traditional ileostomy, the stent assisted intestinal bypass reduces trauma with lower expenses and improves patients' status after laparoscopic low anterior resection for rectal cancer.

Bisecting N-acetylglucosamine(GlcNAc),a GlcNAc linked to the core β-mannose resi-due via a β1,4 linkage,is a special type of N-glycosylation that has been reported to be involved in various biological processes,such as cell adhesion and fetal development.This N-glycan structure is abundant in human trophoblasts,which is postulated to be resistant to natural killer cell-mediated cytotoxicity,enabling a mother to nourish a fetus without rejection.In this study,we hypothesized that the human amniotic membrane,which serves as the last barrier for the fetus,may also express bisected-type glycans.To test this hypothesis,glycomic analysis of the human amniotic membrane was performed,and bisected N-glycans were detected.Furthermore,our pro-teomic data,which have been previously employed to explore human missing proteins,were ana-lyzed and the presence of bisecting GlcNAc-modified peptides was confirmed.A total of 41 glycoproteins with 43 glycopeptides were found to possess a bisecting GlcNAc,and 25 of these gly-coproteins were reported to exhibit this type of modification for the first time.These results provide insights into the potential roles of bisecting GlcNAc modification in the human amniotic membrane,and can be beneficial to functional studies on glycoproteins with bisecting GlcNAc modifications and functional studies on immune suppression in human placenta.

Purpose: Reduced quality of life after cystectomy has made bladder preservation a popular research topic for muscle-invasive bladder cancer (MIBC). Previous research has indicated significant tumor downstaging after neoadjuvant chemotherapy (NAC). However, maximal transurethral resection of bladder tumor (TURBT) was performed before NAC to define the pathology, impacting the real evaluation of NAC. This research aimed to assess real NAC efficacy without interference from TURBT and apply combined modality therapies guided by NAC efficacy. Materials and Methods: Patients with cT2-4aN0M0 MIBC were confirmed by cystoscopic biopsy and imaging. NAC efficacy was assessed by imaging, urine cytology, and cystoscopy with multidisciplinary team discussion. Definite responders (≤ T1) underwent TURBT plus concurrent chemoradiotherapy. Incomplete responders underwent radical cystectomy or partial cystectomy if feasible. The primary endpoint was the bladder preservation rate. Results: Fifty-nine patients were enrolled, and the median age was 63 years. Patients with cT3-4 accounted for 75%. The median number of NAC cycles was three. Definite responders were 52.5%. The complete response (CR) was 10.2%, and 59.3% of patients received bladder-sparing treatments. With a median follow-up of 44.6 months, the 3-year overall survival (OS) was 72.8%. Three-year OS and relapse-free survival were 88.4% and 60.0% in the bladder-sparing group but only 74.3% and 37.5% in the cystectomy group. The evaluations of preserved bladder function were satisfactory. Conclusion After stratifying MIBC patients by NAC efficacy, definite responders achieved a satisfactory bladder-sparing rate, prognosis, and bladder function. The CR rate reflected the real NAC efficacy for MIBC. This therapy is worth verifying through multicenter research.

Bladder cancer is one of the tenth most common malignant tumors in Chinese men. Almost 20% to 30% patients are diagnosed as the muscle-invasive bladder cancer (MIBC) at the first diagnosis.In the past, radical cystectomy (RC) was the first-line treatment with MIBC.The current researches' results show that, neoadjuvant chemotherapy combined with RC can improve the tumor complete response rate and prolong the overall survival of patients with MIBC, comparing with the RC alone. It has become the recommended standard first line treatment for MIBC, which has the possiblity of preserving bladder. Lots of researches indicate that the application of cisplatin-based neoadjuvant chemotherapy in patients with MIBC is becoming more and more popular. However, there is still the possibility of ineffectiveness or tumor progression. Therefore, discussions about the sensitivity of neoadjuvant chemotherapy have always been a hot spot in urological tumor research. In order to provide guidance and help for clinical work, the article reviews the sensitivity of neoadjuvant chemotherapy of bladder urothelial carcinoma.