【Objective】 To explore the safety of transrectal ultrasound-guided transperineal injection of sodium hyaluronate to expand the Dirichlet gap in laparoscopic radical prostatectomy. 【Methods】 A total of 14 healthy male purebred beagle dogs were selected and randomly divided into 2 groups, with 7 in either group.The control group was treated with conventional laparoscopic radical prostatectomy, while the experimental group was treated with laparoscopic radical prostatectomy after 2.5 mL sodium hyaluronate was injected into the Dirichlet gap under the guidance of transrectal ultrasound.The total operation time, prostate separation time, intraoperative blood loss and rectal status of the 2 groups were observed. 【Results】 After the injection of sodium hyaluronate into the Dirichlet gap between the prostate and the rectum, no rectal tissue was found in the prostate, and no obvious damage was found in the posterior rectum in either groups.The postoperative hemoglobin (HGB) was [(118.70±2.56) g/L vs.(122.10±2.19) g/L, P=0.02]; the total operation time was [(141.40±9.80) min vs.(119.10±9.16) min, P<0.05]; the prostate separation time was [(24.99±1.75) min vs.(16.64±2.34) min, P<0.05]; the amount of bleeding was [(47.43±4.32) mL vs.(34.86±5.18) mL, P<0.05] in the control group and experimental group. 【Conclusion】 Laparoscopic radical prostatectomy performed after 2.5 mL of sodium hyaluronate injection into the Dirichlet gap under the guidance of transrectal ultrasound can shorten the total operation time, the separation and resection time of the prostate, and reduce the amount of bleeding, which can improve and reduce the incidence of rectal injury, and prove the feasibility of this approach for prostatic cancer.

Objective To assess the effect of platycodin D(PD)for alleviating pulmonary fibrosis in mice and explore the underlying mechanism.Methods C57BL/6J mouse models of pulmonary fibrosis induced by bleomycin injection into the airway were treated with daily intragastric administration of 10 mg/kg PD for 28 days.The changes of pulmonary fibrosis and the expression and distribution of transient receptor potential cation channel subfamily C member 6(TRPC6)were evaluated with immunohistochemistry,HE staining and Sirius Red staining.Western blotting was used to detect α-SMA expression in the lung tissues of the mice.Primary cultures of mouse lung fibroblasts were pretreated with PD(2.5,5.0,and 10 μmol/L)or larixyl acetate(LA;10 μmol/L)before exposure to 10 ng/mL transforming growth factor-β1(TGF-β1),and the changes in cell survival rate,expressions of collagen I,α-SMA and TRPC6,reactive oxygen species(ROS)production,mitochondrial membrane potential,and cell proliferation capacity were assessed.Network pharmacology analysis was performed to explore the mechanism by which PD alleviated pulmonary fibrosis.Results PD treatment significantly alleviated pulmonary fibrosis and reduced α-SMA expression in BLM-induced mouse models(P<0.05).In TGF-β1-induced primary mouse lung fibroblasts,PD effectively inhibited the cell proliferation,reduced ROS production(P<0.0001),rescued the reduction of mitochondrial membrane potential(P<0.001),and inhibited the expressions of α-SMA and collagenⅠ(P<0.05).Network pharmacology analysis suggested that TRPC6 mediated the effect of PD for alleviating pulmonary fibrosis.Immunohistochemistry showed that PD significantly reduced TRPC6 expression in the lung tissues of BLM-induced mice.In primary mouse lung fibroblasts,PD significantly inhibited TGF-β1-induced TRPC6 expression(P<0.05),and LA treatment obviously lowered the expression levels of TRPC6,α-SMA and collagenⅠ(P<0.05).Conclusion PD alleviated pulmonary fibrosis in mice possibly by down-regulating TRPC6 and reducing ROS production.

Objective To assess the effect of platycodin D(PD)for alleviating pulmonary fibrosis in mice and explore the underlying mechanism.Methods C57BL/6J mouse models of pulmonary fibrosis induced by bleomycin injection into the airway were treated with daily intragastric administration of 10 mg/kg PD for 28 days.The changes of pulmonary fibrosis and the expression and distribution of transient receptor potential cation channel subfamily C member 6(TRPC6)were evaluated with immunohistochemistry,HE staining and Sirius Red staining.Western blotting was used to detect α-SMA expression in the lung tissues of the mice.Primary cultures of mouse lung fibroblasts were pretreated with PD(2.5,5.0,and 10 μmol/L)or larixyl acetate(LA;10 μmol/L)before exposure to 10 ng/mL transforming growth factor-β1(TGF-β1),and the changes in cell survival rate,expressions of collagen I,α-SMA and TRPC6,reactive oxygen species(ROS)production,mitochondrial membrane potential,and cell proliferation capacity were assessed.Network pharmacology analysis was performed to explore the mechanism by which PD alleviated pulmonary fibrosis.Results PD treatment significantly alleviated pulmonary fibrosis and reduced α-SMA expression in BLM-induced mouse models(P<0.05).In TGF-β1-induced primary mouse lung fibroblasts,PD effectively inhibited the cell proliferation,reduced ROS production(P<0.0001),rescued the reduction of mitochondrial membrane potential(P<0.001),and inhibited the expressions of α-SMA and collagenⅠ(P<0.05).Network pharmacology analysis suggested that TRPC6 mediated the effect of PD for alleviating pulmonary fibrosis.Immunohistochemistry showed that PD significantly reduced TRPC6 expression in the lung tissues of BLM-induced mice.In primary mouse lung fibroblasts,PD significantly inhibited TGF-β1-induced TRPC6 expression(P<0.05),and LA treatment obviously lowered the expression levels of TRPC6,α-SMA and collagenⅠ(P<0.05).Conclusion PD alleviated pulmonary fibrosis in mice possibly by down-regulating TRPC6 and reducing ROS production.

Objective:To explore the mechanism of hepatitis B virus(HBV)inhibiting M1 macrophages to promote immune escape,and to provide targets and strategies for antiviral therapy.Methods:The human monocyte cell line THP-1 was induced into M1 macrophages with PMA+LPS+IFN-γ.Cell morphological changes and the expressions of CD68,CD86,HLA-DR and functional molecules IL-1β,IL-6,TNF-α in M1 macrophages were detected by flow cytometry and RT-qPCR to identify M1 macrophages.HBV stable replication cell line HepG2.2.15 were co-cultured with M1 macrophages,and the expression of HBV-DNA was detected by qP-CR.The expression of CD68,CD86 and HLA-DR were detected by flow cytometry.The expressions of functional molecules TLR4,NLRP3,Caspase-1,pro-caspase-1,caspase-1 p20,IL-1β and IL-18 in M1 macrophages were determined by RT-qPCR and Western blot.Apoptosis rate was detected by flow cytometry,and the expression of apoptosis related protein cleaved-caspase-3 was determined by Western blot.Results:THP-1 was successfully induced to differentiate into M1 macrophages.M1 macrophages inhibited HBV repli-cation(P<0.05).HBV inhibited the expressions of CD68,CD86 and HLA-DR in M1 macrophages(P<0.01).HBV inhibited the ex-pressions of TLR4,NLRP3,Caspase-1,caspase-1 p20,IL-1β and IL-18 in M1 macrophages(P<0.01).HBV induced M1 macro-phage apoptosis(P<0.05).Conclusion:HBV inhibits M1 macrophages and their functional molecules TLR4,NLRP3 and down-stream factors,reduces the synthesis and secretion of inflammatory factors,induces apoptosis,and then promotes immune escape,re-sulting in the persistence and replication of HBV in the body.

Animals ; Humans ; Thymic Stromal Lymphopoietin ; Pyroglyphidae/metabolism* ; Cytokines/metabolism* ; Asthma/metabolism* ; Respiratory System ; Epithelial Cells/metabolism*

Background: Acute non-variceal upper gastrointestinal bleeding (ANVUGIB) is one of the most common acute and severe clinical entities. As the limited medical resource in remote regions or primary hospitals, it is necessary to explore an effective endoscopic hemostasis method in such a medical condition. Aims: To investigate the efficacy of norepinephrine injection combined with electrocoagulation under conventional endoscopy in patients with ANVUGIB. Methods: Clinical data of 123 ANVUGIB patients were collected retrospectively from January 2019 to December 2021 at the Kashgar Prefecture Second People’s Hospital. According to the endoscopic hemostasis method used initially, these patients were divided into group A (submucosal injection of norepinephrine), group B (electrocoagulation), group C (clip hemostasis) and group D (direct norepinephrine injection combined with electrocoagulation). The success rate of immediate hemostasis, operation time, rebleeding rate within 72 hours, and rate of transfer to surgery were compared between the four groups. Furthermore, the relationship between visual field during hemostasis and success of immediate hemostasis was analyzed. Results: In group D, all patients achieved success immediate hemostasis, the success rate (100%) was significantly higher than that in group A, group B, and group C (all P<0.05). No rebleeding and surgical transfer was observed in group D. The operation time of group D was (17.84±6.78) min, which was not significantly different from that of group A and group C (all P>0.05). In patients treated with combined hemostasis, including initial combination strategy and failed cases transferred to combination strategy, a clear endoscopic visual field could be obtained in 94.2% of the cases, and the success rate of immediate hemostasis was 98.1%. Conclusions: Submucosal injection of norepinephrine combined with electrocoagulation under conventional endoscopy has a higher immediate hemostasis rate with lower rates of rebleeding and surgical transfer in ANVUGIB patients. This strategy is worthy for popularizing in remote regions and primary hospitals.

Interferon-γ (IFN-γ), a key effector molecule in anti-tumor immune response, has been well documented to correlate with the intratumoral infiltration of immune cells. Of interest, however, a high level of IFN-γ has been reported in salivary adenoid cystic carcinoma (SACC), which is actually a type of immunologically cold cancer with few infiltrated immune cells. Investigating the functional significance of IFN-γ in SACC would help to explain such a paradoxical phenomenon. In the present study, we revealed that, compared to oral squamous cell carcinoma cells (a type of immunologically hot cancer), SACC cells were less sensitive to the growth-inhibition effect of IFN-γ. Moreover, the migration and invasion abilities of SACC cells were obviously enhanced upon IFN-γ treatment. In addition, our results revealed that exposure to IFN-γ significantly up-regulated the level of programmed death ligand 1 (PD-L1) on SACC cell-derived small extracellular vesicles (sEVs), which subsequently induced the apoptosis of CD8⁺ T cells through antagonizing PD-1. Importantly, it was also found that SACC patients with higher levels of plasma IFN-γ also had higher levels of circulating sEVs that carried PD-L1 on their surface. Our study unveils a mechanism that IFN-γ induces immunosuppression in SACC via sEV PD-L1, which would account for the scarce immune cell infiltration and insensitivity to immunotherapy.
B7-H1 Antigen/metabolism* ; CD8-Positive T-Lymphocytes/pathology* ; Carcinoma, Adenoid Cystic/pathology* ; Carcinoma, Squamous Cell/pathology* ; Cell Line, Tumor ; Humans ; Immunosuppression Therapy ; Interferon-gamma/pharmacology* ; Mouth Neoplasms/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Salivary Gland Neoplasms/pathology*

Ulcerative colitis(UC)is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis.Previous studies have indicated that celastrol(CSR)has strong anti-inflammatory and immune-inhibitory effects.Here,we investigated the effects of CSR on colonic inflammation and mucosal immunity in an experimental colitis model,and addressed the mechanism by which CSR exerts the protective effects.We characterized the ther-apeutic effects and the potential mechanism of CSR on treating UC using histological staining,intestinal permeability assay,cytokine assay,flow cytometry,fecal microbiota transplantation(FMT),16S rRNA sequencing,untargeted metabolomics,and cell differentiation.CSR administra-tion significantly ameliorated the dextran sodium sulfate(DSS)-induced colitis in mice,which was evidenced by the recovered body weight and colon length as well as the decreased disease activity index(DAI)score and intestinal permeability.Meanwhile,CSR down-regulated the production of pro-inflammatory cytokines and up-regulated the amount of anti-inflammatory mediators at both mRNA and protein levels,and improved the balances of Treg/Thl and Treg/Th1 7 to maintain the colonic immune homeostasis.Notably,all the therapeutic effects were exerted in a gut microbiota-dependent manner.Furthermore,CSR treatment increased the gut microbiota diversity and changed the compositions of the gut microbiota and metabolites,which is probably associated with the gut microbiota-mediated protective effects.In conclusion,this study provides the strong evidence that CSR may be a promising therapeutic drug for UC.

The patient, male, 1 year, was admitted to our hospital with cardiac murmur. Cardiac ultrasonography showed "complete atrioventricular septal defect (C-AVSD), secondary orifice atrial septal defect (ASD), patent ductus arteriosus (PDA), left superior vena cava, and pulmonary hypertension". The patient got follow-up at the age of 3, 6, 9 months and 1 year, with no feeding difficulties, no obvious underdevelopment and no history of repeated respiratory infections. Cardiac ultrasonography showed that the ventricular septal defect (VSD) healed spontaneously at 9 months of age. At 1 year of age, he was admitted to the hospital with "partial atrioventricular septal defect (P-AVSD)" and accepted surgery. Intraoperative exploration showed that the primary orifice ASD was 12 mm, the atrioventricular valve was divided into two groups, and the left atrioventricular valve had three leaflets: anterior, posterior, and lateral one. A cleft was between the anterior and posterior leaflets. The annulus was not enlarged with diameter of 13 mm. The right atrioventricular valve developed well, with fibrous hyperplasia and adhesion under the septal valve. No VSD was seen. The cleft was sutured intermittently. Autologous pericardial patch was used to repair the primary orifice ASD, and the coronary sinus was separated into the right atrium. Self-healing of VSD patients with C-AVSD is very rare, suggesting that patients with C-AVSD with normal range of development, and without obvious clinical symptoms and secondary damage, should be followed up and accept elective surgery in clinical practice.

Objective To investigate the expression of microRNA-1290 in pancreatic cancer and its role in invasion and metastasis of pancreatic cancer.Methods The expression of microRNA-1290 in pancreatic cancer tissue microarray and pancreatic cancer cell lines (AsPC-1,BxPC-3,Capan-2,Panc-1,and MIA PaCa-2) were detected by immunohistochemistry and QT-PCR.The pancreatic cancer cell lines Panc-1 and MIA PaCa-2 in logarithmic growth phase were treated with microRNA-1290 inhibitor,and the invasion and metastasis ability of pancreatic cancer cells were detected by Transwell and wound healing asssay.Western Blot was used to detect the expression of invasion and metastasis-associated proteins cyclooxygenase 2 (COX-2) and matrix metalloproteinase 2(MMP-2) in pancreatic cancer cell lines.Results (1) The expression of microRNA-1290 in pancreatic cancer tissues was significantly higher than that in normal pancreatic tissues and adjacent tissues (P ＜ 0.05).(2) Compared with pancreatic normal epithelial cells (HPDE),the expression of microRNA-1290 was significantly higher in different pancreatic cancer cell lines (P ＜ 0.05).The expression level of MicroRNA-1290 in Panc-1 and MIAPaCa-2 pancreatic cancer cells was significantly higher than that in other pancreatic cancer cell lines (P ＜ 0.05).(3) The number of invasive and metastatic cells was significantly decreased after treatment with microRNA-1290 inhibitor (P ＜0.05).(4) The expression of MMP-2 and COX-2 were decreased in Panc-1 and MIAPaCa-2 pancreatic cancer cells treated with MicroRNA-1290 inhibitor.Conclusion The expression of MMP-2 and COX-2 may be involved in the invasion and metastasis of pancreatic cancer cell by regulating the expression of microRNA-1290 in pancreatic cancer.