[Objective] To explore the expression of Nectin-4 in invasive bladder urothelial carcinoma (BUC) tissue and its clinical significance, so as to provide reference for clinical diagnosis and treatment of BUC. [Methods] Nectin-4 expression in 60 cases of invasive BUC and 40 cases of chronic inflammation of bladder mucosa was detected with immunohistochemical staining (IHC) and RNAscope.The results of the two methods were analyzed and compared, and the relationship between the two methods and the clinicopathological characteristics of invasive BUC was discussed.The correlation between the protein expression of Nectin-4 in BUC tissues, human epidermal growth factor receptor 2 (Her-2) and programmed death factor ligand 1 (PD-L1) was analyzed. [Results] The positive protein expression rates of Nectin-4 detected by IHC were 78.33%(47/60) and 17.50% (7/40) in the invasive BUC group and inflammatory group, respectively, while the positive mRNA expression rates of Nectin-4 detected by RNAscope were 83.33% (50/60) and 12.50% (5/40), respectively.The Kappa values of Nectin-4 in the invasive BUC group and inflammatory group were 0.732 and 0.610, respectively, with general consistency.The protein expression of Nectin-4 in invasive BUC was correlated with muscular invasion, histological grade, vascular thrombus, lymph node metastasis and clinical stage (P<0.05). The mRNA expression of Nectin-4 in invasive BUC was correlated with max tumor diameter, muscular invasion, histological grade, vascular thrombus, lymph node metastasis and clinical stage (P<0.05). The high expression of Nectin-4 in invasive BUC was positively correlated with the expression of Her-2 (P=0.002), but not with the expression of PD-L1 (P>0.05). [Conclusion] Nectin-4 is highly expressed in invasive BUC, and is usually associated with the pathological parameters of poor prognosis.Detection of Nectin-4 expression will help to guide clinical diagnosis and treatment.

Objective To investigate the clinical features and prognosis of hepatocellular carcinoma(HCC).Methods Medical records were collected from 850 HCC patients who were admitted to Hubei Provincial Hospital of Traditional Chinese Medicine from December 2014 to May 2022,and their clinical and prognostic features were analyzed.The chi-square test were used for comparison of categorical data between groups;the Kaplan-Meier method was used to calculate survival time and survival rate,and the log-rank test was used for comparison of survival time based on baseline features.Results Among the 850 HCC patients,male patients accounted for 82.6%,and the median age at initial diagnosis was 58.0(49.0,66.0)years,with the highest proportion of patients aged 50-69 years(59.8%).The patients with HBV infection accounted for the highest proportion of 77.4%;at initial diagnosis,49.2%of the patients had portal vein tumor thrombus,and 20.2%of the patients had extrahepatic metastasis,among which pulmonary metastasis accounted for the highest proportion of 44.2%(76/172).The patients with Barcelona Clinic Liver Cancer(BCLC)stage A(0),B,C,and D HCC accounted for 20.4%,22.5%,41.5%,and 15.6%,respectively.There was a significant difference in the distribution of BCLC stages between different groups based on sex(χ2=16.631,P=0.001),age(χ2=24.261,P=0.019),place of residence(χ2=39.776,P＜0.001),presence or absence of viral hepatitis(χ2=8.338,P=0.040),and presence or absence of regular antiviral therapy before initial diagnosis(χ2=26.140,P＜0.001).Follow-up was performed for 489 patients till death,with a median survival time of 19.99 months(95%confidence interval[CI]:14.86-25.12),and the 1-,3-,5-,and 10-year cumulative survival rates were 60.7%,39.9%,29.4%,and 22.7%,respectively.There was a significant difference in survival time between different groups based on age(χ2=13.452,P=0.009),history of viral hepatitis(χ2=6.123,P=0.013),regular antiviral therapy before initial diagnosis(χ2=15.505,P＜0.001),comorbidity with type 2 diabetes(χ2=9.820,P=0.002),the number of tumors(χ2=57.713,P＜0.001),maximum tumor diameter(χ2=41.862,P＜0.001),portal vein tumor thrombus(χ2=293.909,P＜0.001),extrahepatic metastasis at initial diagnosis(χ2=118.329,P＜0.001),BCLC stage(χ2=465.638,P＜0.001),surgical resection(χ2=78.86,P＜0.001),local treatment(χ2=36.216,P＜0.001),immune checkpoint inhibitor treatment and/or anti-tumor angiogenesis therapy(χ2=7.182,P=0.007),traditional Chinese medicine decoction treatment(χ2=30.050,P＜0.001),and comprehensive treatment regimens(χ2=13.221,P=0.004).Progression-free survival(PFS)was recorded for 259 patients(30.5%),with a median PFS of 10.98 months(95%CI:8.54-13.42).Conclusion HCC patients exhibit epidemiological characteristics in terms of sex,age,place of residence,presence or absence of viral hepatitis,regular antiviral therapy before initial diagnosis,tumor characteristics,treatment modality,and prognosis,with a low early detection rate and a short overall survival time,and therefore,it is urgent to perform early screening,early diagnosis,and early treatment.

AIM:To observe the vascular remodel-ing of eriodictyol(EDT)in spontaneously hyperten-sive rats(SHRs)by inhibiting TLR4/NF-kB signaling and to investigate the potential mechanism of ac-tion.METHODS:WKY normal control,SHRs model and EDT administration(EDT 120 mg/kg,SHRs+EDT)group were set for 20 weeks.Tail cuff method for blood BP measurement(SBP,DBP and MBP).Ul-trasonic detection of pulse wave velocity(PWV).The aortic media membrane thickness(MT)was vi-sualized by HE staining.The percentage of aortic collagen(VFC)changes were observed by MASSON staining,Serum content of TNF-α,IL-6,and IL-10 was measured by ELISA.The TNF-α,IL-6,and IL-10 mRNA changes in the aorta were detected by q-PCR.The aortic Collagen Ⅰ and Collagen Ⅲ expres-sion was observed by immunohistochemistry,WB measured the expression of aortic TGF-β1,MMP-2,MMP-9,TLR4,p-IκBa,IκBa,p-p65 and p65.RE-SULTS:After 20 weeks of EDT administration,SBP,DBP,MBP and PWV of SHRs were significantly de-creased,MT and VFC of aorta were significantly de-creased,and protein expressions of Collagen Ⅰ,Col-lagen Ⅲ,TGF-β1,MMP-2,MMP-9,TLR4,p-l Camba and p-p65 were significantly decreased.CONCLU-SION:After long-term administration of EDT could inhibit TLR4/NF-κB signaling and exert anti-inflam-matory effects,thus reducing TGF-β1,MMP-2 and MMP-9 expression,decreasing collagen content,and finally improving aortic remodeling and sclero-sis of SHRs.

A colon-specific drug delivery system has great potential for the oral administration of colorectal cancer. However, the uncontrollable in vivo fate of liposomes makes their effectiveness for colonic location, and intratumoral accumulation remains unsatisfactory. Here, an oral colon-specific drug delivery system (CBS-CS@Lipo/Oxp/MTZ) was constructed by covalently conjugating Clostridium butyricum spores (CBS) with drugs loaded chitosan (CS)-coated liposomes, where the model chemotherapy drug oxaliplatin (Oxp) and anti-anaerobic bacteria agent metronidazole (MTZ) were loaded. Following oral administration, CBS germinated into Clostridium butyricum (CB) and colonized in the colon. Combined with colonic specifically β-glucosidase responsive degrading of CS, dual colon-specific release of liposomes was achieved. And the accumulation of liposomes at the CRC site furtherly increased by 2.68-fold. Simultaneously, the released liposomes penetrated deep tumor tissue via the permeation enhancement effect of CS to kill localized intratumoral bacteria. Collaborating with blocking the translocation of intestinal pathogenic bacteria from lumen to tumor with the gut microbiota modulation of CB, the intratumoral pathogenic bacteria were eliminated fundamentally, blocking their recruitment to immunosuppressive cells. Furtherly, synchronized with lipopolysaccharide (LPS) released from MTZ-induced dead Fusobacterium nucleatum and the tumor-associated antigens produced by Oxp-caused immunogenic dead cells, they jointly enhanced tumor infiltration of CD8⁺ T cells and reactivated robust antitumor immunity.

BACKGROUND: Clinical trial evidence is limited to identify better topical non-steroidal anti-inflammatory drugs (NSAIDs) for treating knee osteoarthritis (OA). We aimed to compare the clinical efficacy and safety of flurbiprofen cataplasms (FPC) with loxoprofen sodium cataplasms (LSC) in treating patients with knee OA. METHODS: This is an open-label, non-inferiority randomized controlled trial conducted at Peking University Shougang Hospital. Overall, 250 patients with knee OA admitted from October 2021 to April 2022 were randomly assigned to FPC and LSC treatment groups in a 1:1 ratio. Both medications were administered to patients for 28 days. The primary outcome was the change of pain measured by visual analog scale (VAS) score from baseline to day 28 (range, 0-10 points; higher score indicates worse pain; non-inferiority margin: 1 point; superiority margin: 0 point). There were four secondary outcomes, including the extent of pain relief, the change trends of VAS scores, joint function scores measured by the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and adverse events. RESULTS: Among 250 randomized patients (One patient without complete baseline record in the flurbiprofen cataplasms was excluded; age, 62.8 ± 10.5 years; 61.4% [153/249] women), 234 (93.6%) finally completed the trial. In the intention-to-treat analysis, the decline of the VAS score for the 24-h most intense pain in the FPC group was non-inferior, and also superior to that in the LSC group (differences and 95% confidence interval, 0.414 (0.147-0.681); P <0.001 for non-inferiority; P = 0.001 for superiority). Similar results were observed of the VAS scores for the current pain and pain during exercise. WOMAC scores were also lower in the FPC group at week 4 (12.50 [8.00-22.50] vs . 16.00 [11.00-27.00], P = 0.010), mainly driven by the dimension of daily activity difficulty. In addition, the FPC group experienced a significantly lower incidence of adverse events (5.6% [7/124] vs . 33.6% [42/125], P <0.001), including irritation, rash and pain of the skin, and sticky hair uncovering pain. CONCLUSIONS This study suggested that FPC is superior to LSC for treating patients with knee OA in pain relief, joint function improvement, and safety profile.
Humans ; Female ; Middle Aged ; Aged ; Osteoarthritis, Knee/drug therapy* ; Flurbiprofen/therapeutic use* ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use* ; Pain/drug therapy* ; Treatment Outcome ; Double-Blind Method

AIM: To observe the effect of metformin (Met) on the endothelial-mesenchymal transition (EMT) of rat alveolar epithelial type II cells and its mechanism. METHODS: The RLE-6TN cells were divided into 6 groups as follows: Control group; transforming growth factor-β

【Objective】 To investigate the relationship between anti-platelet antibodies, therapeutic effect of intravenous immunoglobulin (IVIG) and Treg/Th17 cells imbalance in children with immune thrombocytopenia (ITP). 【Methods】 The changes and correlation of platelet count and Treg/Th17 ratio before and after IVIG treatment in 60 newly diagnosed ITP children with anti-platelet antibodies and 60 children with primary ITP without anti-platelet antibodies were analyzed. 【Results】 1) Compared with the control group, the efficacy of IVIG treatment was better in children with ITP in the case group(CR+ R cases: 50 vs 32) (P<0.01). 2) After IVIG treatment, platelet count(×10⁹/L)(case: 4.5±2.9 vs 327.4±69.5, control: 4.1±3.2 vs 304.7±75.9), Treg cell level(%)(case: 2.15±1.08 vs 5.09±1.37, control: 2.41±0.92 vs 4.98±1.10), Treg/Th17 ratio(case: 1.10±0.19 vs 7.75±1.11, control: 1.27±0.21 vs 4.69±0.81)significantly increased while Th17 cell level(%) significantly decreased in the 2 groups of children(case: 2.07±1.31 vs 1.37±0.92, control: 2.13±1.18 vs 1.48±1.01); compared with the control group, there was no significant change in Treg, Th17 and Treg/Th17 ratio before and after treatment in the case group (P>0.05), but platelet count increased more significantly (P<0.05). 3) There were 3 positive cases in the control group and 12 negative cases in the case group after IVIG treatment, and IVIG treatment probably had no effect on the positive rate of anti-platelet antibodies in children with ITP (P>0.05). 4) The change in platelet count after IVIG treatment was significantly positively correlated with Treg levels (r=0.49 in the case group and r=0.441 in the control group) and negatively correlated with Th17 cell levels (r=-0.390 in the case group and r=-0.364 in the control group). 【Conclusion】 Anti-platelet antibodies can be used as a predictor of the efficacy of IVIG therapy in children with ITP, but they are not associated with changes in the Treg/Th17 ratio.

Objective To establish a reliable pretreatment method for the detection of mequindox and its metabolite in pork luncheon meat by ultra-performance liquid chromatography/triple qudrupole tandem mass spectrometry. Methods Samples were extracted with ethyl acetate, and the results of purification and enrichment by PAX and PEP solid-phase extraction columns were analyzed. Acetonitrile/methanol (3:11) - 0.1% formic acid water was used as the mobile phase, and Shimadzu Inertsil ODS-3-column (3µm, 2.1 × 100mm) chromatographic columns were used for qualitative and quantitative analysis using the multi-reaction detection positive ion mode. Results The results showed that PEP cartridge had good recovery rate. The detection limit of mequindox was 0.10µg/kg, and limit of quantitation was 0.30µg/kg. The average recoveries for spiked levels of 0.33, 0.83, and 1.65µg/kg were 127%, 72.0%, and 60.1%, respectively. The detection limit of 2-quinoxalinecarboxylic acid was 0.10µg/kg, and limit of quantitation was 0.40µg/kg. The average recoveries for spiked levels of 0.42, 1.05, and 2.1µg/kg were 125%, 99.0%, and 60.9%, respectively. Conclusion This method is suitable for the determination of mequindox and its metabolite 2-quinoxalinecarboxylic acid in luncheon meat.

AIM: Sesamin (Ses) is one of the major lignans in sesame seeds with antihypertensive and antifibroticactivities, but its effect is weak. In this experiment, we combined vitamin E (VitE) and Ses to observe their effects on blood pressure and left ventricular fibrosis in spontaneously hypertensive rats (SHRs), and to explore its possible mechanism. METHODS: Male SHRs were randomly divided into SHRs+Ses+VitE group, SHRs+Ses group, SHRs+VitE group, and SHRs model group. Wistar-Kyoto (WKY) rats were setted as a normal control group. After 10 weeks of administration, systolic blood pressure (SBP) of rats was measured by tail cuff method, and the left ventricle was taken to calculate the organ index. Collagen deposition was observed by Masson staining, and cardiac collagen volume fraction (CVF) was analyzed. Expressions of collagen I, collagen III, transforming growth factor-β

Fecal microbiota transplantation(FMT) is a new treatment method for intestinal diseases, especially for recurrent Clostridium difficile infection(CDI), which is very effective.It can reconstruct the intestinal flora of patients and effectively correct the disorder of intestinal flora.In recent years, the clinical application of fecal transplantation has been more and more extensive.This paper reviews the development history, operation process, clinical application and adverse reactions of fecal transplantation.