OBJECTIVE:To observe the effects of Gegenqinlian colon positioning tablet(GGQLJC)on colon tissue PPAR-γ, NF-κB p65 protein expressions of model rabbits with damp-heat type ulcerative colitis(UC). METHODS:56 rabbits were random-ly divided into normal group(normal saline),model group(normal saline),sulfasalazine tablet(SASP)group(positive control, 0.300 g/kg),Gegenqinlian tablet (GGQL) group (0.225 g/kg) and GGQLJC high-dose,medium-dose,low-dose groups (1.036, 0.518,0.259 g/kg),8 in each group. Except for normal group,rabbits in other groups were cultured for damp-heat-type UC mod-el,intragastrically administrated in the second day of last administration,once a day,for 14 d. Disease activity index(DAI),co-lonic mucosal damage index (CMDI),histological damage (TDI) were scored;colon,spleen and thymus indexes were deter-mined;PPAR-γ,NF-κB p65 protein expressions in colon tissue were detected. RESULTS:Compared with normal group,DAI, CMDI,TDI scores and spleen index,colon index,NF-κB p65 protein level in colon tissue in model group were significantly in-creased(P<0.01);thymus index,PPAR-γprotein level in colon tissue were significantly reduced(P<0.01). Compared with mod-el group,above-mentioned indexes in each administration group were significantly improved (P<0.05 or P<0.01). Compared with GGQL group,DAI and TDI scores,spleen index,colon index,NF-κB p65 protein level in colon tissue in SASP group, GGQLJC high-dose,medium-dose groups were significantly decreased (P<0.05);PPAR-γ protein level in colon tissue in SASP group,GGQLJC high-dose,medium-dose groups were significantly increased (P<0.05 or P<0.01). CONCLUSIONS:GGQLJC has certain improvement effects on model rabbits with damp-heat type UC,which is superior to GGQL. The mechanism may be re-lated to increasing PPAR-γprotein level and decreasing NF-κB p65 protein level in colon tissue.

Objective To study absorption characteristic of dioscin from Dioscorea nipponica Makino extract in rat intestine.Methods Single-pass intestinal perfusion (SPIP) model was used for rat in situ and HPLC was used to determine the concentrations of dioscin.The effects of different intestinal segments,drug concentration and P-glycoprotein (P-gp) inhibitor on intestinal absorption were investigated.Results Dioscin could be absorbed in the whole intestine,the absorption rate constant (Ka) and the apparent coefficient (Papp) of dioscin decreased following the sequence of ileum > duodenum =jejunum > colon.Absorption parameters of dioscin had no significant difference at different concentrations (40,80,120 mg·L-1).There were significant differences in Ka and Papp values between P-gp inhibitor group and no P-gp inhibitor group(P<0.05).Conclusion The saturate phenomena was not observed under the test range of drug concentration,and the absorption mechanism may be passive diffusion transport.Dioscin in Dioscorea nipponica Makino extract may be the substrate of P-gp.

OBJECTIVETo evaluate the down stream involvement of the bile duct in hepatolithiasis.

METHODSMechanical damage to bile duct epithelia and long standing cholangitis as result of hepatolithiasis play an important role in the carcinogenesis of bile duct epithelia and stricture of the intra- and extra-hepatic bile duct. Macromorphological and microscopic changes in bile duct mucosa of 100 consecutive patients with hepatolithiasis were investigated using intra- or post-operative cholangioscopy. Biopsy specimens of lesions obtained during cholangioscopy were studied with immunohistochemical staining and flow cytometry to determine proliferative activity and DNA content. Five cases of well-proven cholangiocarcinoma were simultaneously studied as controls.

RESULTSOf the 100 patients, those with chronic cholangitis accounted for 86% (86/100), proliferative lesions 11% (11/100), adenomatous polyps 1% (1/100), and adenocarcinoma 2% (2/100). The obvious mucosal lesion associated with hepatolithiasis was located down-stream of the bile duct, predominantly in the hilar region, e.g. orifices of the right/left hepatic duct and common hepatic duct (73% mucosa lesions in the hilar region). The intensity of cancer embryonic antigen stain and the proliferative cell nuclear antigen index increased with the development of bile duct lesions. Aneuploid DNA presented mainly in the high degree malignant adenocarcinomas (> 80% of cases).

CONCLUSIONSThe obvious mucosal lesions associated with hepatolithiasis were located down-stream of the bile duct, predominantly in the hilar region (73% of mucosal lesions). The proliferative activity of examined bile duct mucosa lesions increased with the development of pathological deterioration, which may contribute to the development of hilar bile duct stricture and hilar cholangiocarcinoma.

Adult ; Aged ; Bile Ducts ; pathology ; Carcinoembryonic Antigen ; analysis ; Cholangiocarcinoma ; etiology ; Humans ; Lithiasis ; complications ; pathology ; Liver Diseases ; complications ; pathology ; Middle Aged ; Proliferating Cell Nuclear Antigen ; analysis

Adenoid cystic carcinoma (ACC) is the second most common pathological subtype of malignant tumors of salivary glands. The incidence of recurrence and metastasis is high after initial treatment. The optimal treatment for these patients is still controversial. In recent years, multiple attempts have been made to treat recurrent and / or metastatic ACC, such as radiation therapy, targeted therapy and immunotherapy. In this article, the treatment options for recurrent and / or metastatic ACC was reviewed and the effect and prospect of each treatment were summarized.

Objective To explore the efficacy and safety of TACE combined with propranolol for treating giant infantile hepatic hemangioma(IHH).Methods Ten infants with giant IHH who underwent TACE combined with propranolol were retrospectively enrolled.The technical success rate,complications and recurrence were recorded.The therapeutic effect was evaluated according to clinical symptoms and changes of IHH volume before and 6 months after TACE.Results Totally 15 times of TACE were successfully performed in 10 infants,with technical success rate of 100%.Bleomycin-lipiodol emulsion+poly(vinyl alcohol)(PVA)+coil embolization were performed in 3 cases,while bleomycin-lipiodol emulsion+PVA embolization were performed in 7 cases.Complications of TACE included subcutaneous hematoma around the puncture site in 1 case and transient hypothermia within 24 h after TACE in 2 cases,all alleviated after symptomatic treatments.No other complication occurred.Six months after the last TACE,significantly effective was observed in 9 cases(9/10,90.00%),while effective was noticed in 1 case(1/10,10.00%),with total therapeutic effective rate of 100%.No serious complication such as gallbladder necrosis,liver necrosis,death,nor recurrence of hepatic hemangioma occurred during follow-up.Conclusion TACE combined with propranolol was effective and safe for treating giant IHH.

The clinical and imaging data of 99 patients with Graves′ disease, 78 patients with thyroiditis and 28 patients with other diseases (resolving thyroiditis, non thyroid disease and simple goiter) who underwent thyroid scintigraphy in Beijing Shijingshan Hospital from January 2016 to March 2022 were retrospectively reviewed. The UR value of thyroid scintigraphy was calculated and ROC curve was used to assess the UR value in diagnosis of Graves′ disease. The UR value of patients with Graves′ hyperthyroidism was significantly higher than that of patients with thyroiditis and other diseases ( H=163.62, P<0.05). UR>4.84 was taken as optimal cutoff value to diagnose Graves′ hyperthyroidism, with the sensitivity and specificity of 95.0% and 98.1%, respectively.

Objective:To study the use of different assessment methods in predicting perioperative outcomes in patients with acute cholecystitis and decompensated cirrhosis.Methods:A retrospective study was performed on 28 patients with acute cholecystitis and decompensated cirrhosis (MELD ≥ 15) who underwent laparoscopic surgical intervention from January 2016 to August 2020 at the Third People Hospital of Xinjiang Uygur Autonomous Region. These patients were divided into 2 groups according to the severity of acute cholecystitis grading in the Tokyo Guidelines 2018 (TG18): TG18 grade Ⅰ for the mild cholecystitis group ( n=15) and TG18 grade Ⅱ and grade Ⅲ for the moderate and severe cholecystitis group ( n=13). 16 patients with a MELD score ranging from 5 to 15 and with TG18 grade Ⅰ were used as the control group. The operation-related conditions, surgical injuries and surgical complications were compared among the three groups. Results:Of 44 patients with acute cholecystitis and decompensated cirrhosis included in this study, there were 28 males and 16 females, aged (57.3±5.9) years. Significantly more patients in the moderate and severe cholecystitis group (13/13) suffered from cholecystitis due to stone impaction than the control group (11/16) and the mild cholecystitis group (10/15) ( P<0.05). When compared to the control group, patients in the mild cholecystitis group and the moderate and severe cholecystitis group had significant increases in operative time, intraoperative bleeding, amount of abdominal drainage, abdominal drainage time, delayed feeding time and hospital stay ( P<0.05). These perioperative outcomes were further and significantly increased in the moderate and severe cholecystitis group when compared to the mild cholecystitis group ( P<0.05). The blood bilirubin levels, blood creatinine levels and MELD scores after surgery were significantly better in both the mild cholecystitis group and the moderate and severe cholecystitis group on postoperative day 3 when compared to those before treatment ( P<0.05). The Child score was significantly better in the control group after surgery than that before surgery ( P<0.05). The grade Ⅰ-Ⅱ surgical complication rate was significantly higher in the moderate and severe cholecystitis group (11/13) than the mild cholecystitis group (5/15, χ 2=7.479), and the control group (4/16, χ 2=10.208) ( P<0.05). There were no significant differences in the grade Ⅲ-Ⅴ surgical complication rates among the three groups (all P>0.05). The overall surgical complication rate was significantly higher in the moderate and severe cholecystitis group (12/13) than the mild cholecystitis group (7/15, χ 2=7.385), and the control group (5/16, χ 2=11.023), (all P<0.05). Conclusions:The MELD score when combined with the severity grading for acute cholecystitis of the TG18 was effective to evaluate the perioperative risks of patients with acute cholecystitis and decompensated cirrhosis. Patients with a MELD score ≥ 15 and TG18 Ⅱ or Ⅲ had significantly higher risks after minimally invasive surgery.

Background::With functionally heterogeneous cells, tumors comprise a complex ecosystem to promote tumor adaptability and evolution under strong selective pressure from the given microenvironment. Diversifying tumor cells or intra-tumor heterogeneity is essential for tumor growth, invasion, and immune evasion. However, no reliable method to classify tumor cell subtypes is yet available. In this study, we introduced the single-cell sequencing combined with copy number characteristics to identify the types of tumor cells in microsatellite stable (MSS) colorectal cancer (CRC).Methods::To characterize the somatic copy number alteration (SCNA) of MSS CRC in a single cell profile, we analyzed 26 tissue samples from 19 Korean patients (GSE132465, the Samsung Medical Center [SMC] dataset) and then verified our findings with 15 tissue samples from five Belgian patients (GSE144735, the Katholieke Universiteit Leuven 3 [KUL3] dataset). The Cancer Genome Atlas (TCGA) cohort, GSE39582 cohort, and National Cancer Center (NCC) cohort (24 MSS CRC patients were enrolled in this study between March 2017 and October 2017) were used to validate the clinical features of prognostic signatures.Results::We employed single cell RNA-sequencing data to identify three types of tumor cells in MSS CRC by their SCNA characteristics. Among these three types of tumor cells, C1 and C3 had a higher SCNA burden; C1 had significant chromosome 13 and 20 amplification, whereas C3 was the polar opposite of C1, which exhibited deletion in chromosome 13 and 20. The three types of tumor cells exhibited various functions in the tumor microenvironment and harbored different mutations. C1 and C2 were linked to the immune response and hypoxia, respectively, while C3 was critical for cell adhesion activity and tumor angiogenesis. Additionally, one gene ( OLFM4) was identified as epithelium-specific biomarker of better prognosis of CRC (TCGA cohort: P = 0.0110; GSE39582 cohort: P= 0.0098; NCC cohort: P= 0.0360). Conclusions::On the basis of copy number characteristics, we illustrated tumor heterogeneity in MSS CRC and identified three types of tumor cells with distinct roles in tumor microenvironment. By understanding heterogeneity in the intricate tumor microenvironment, we gained an insight into the mechanisms of tumor evolution, which may support the development of therapeutic strategies.

Objective To explore the effect of decoction of Euphorbia fischeriana Steud.and jujuba(DEFSJ)against estrogen receptor(ER)negative(-)and ER positive(+)breast cancer via the PI3k/Akt pathway,and to provide a reference for the targeted treatment of breast cancer.Methods DEFSJ extract was prepared and analyzed using UHPLC-Triple Quad.DEFSJ containing serum(CS)was prepared via a serum pharmacology method.Different concentrations of DEFSJ-CS were applied to(ER-)MDA-MB-453 and(ER+)MCF-7 breast cancer cells in vitro for 48 h.The distribution of cells in different stages of the cellular cycle was evaluated using a Flow cytometer.DNA ladder assay was used to assess the degree of apoptosis,and the expression of PI3k/Akt pathway-related proteins was evaluated by Western blot assay.The expression of FoxO3a,FoxOla,and Bim mRNA was detected by Real-time quantitative PCR.Nuclear transposition of FoxO3a protein was analysed using a confocal laser microscopy.Results Five batches of DEFSJ extract were analyzed using UPLC,and the result showed that the preparation technology was feasible and the quality was controllable,ensuring the accuracy of the pharmacological experiment result.DEFSJ-CS blocked cells in the G2/M phase(P＜0.05,P＜0.01).Cells treated with DEFSJ-CS displayed the typical apoptotic ladder in the DNA ladder experiment.Compared with the negative control cells,the DEFSJ-CS group cells had decreased protein expression of p-PI3k,p-Akt,p-FoxO3a,and p-FoxO1a(P＜0.05,P＜0.01);increased protein expression of Bim(P＜0.05);decreased mRNA expression of FoxO3a and FoxO1a(P＜0.05,P＜0.01);increased mRNA expression of Bim(P＜0.05,P＜0.01);and enhanced nuclear translocation of FoxO3a protein.The data showed that DEFSJ-CS had a stronger effect on(ER-)MDA-MB-453 cells than(ER+)MCF-7 cells.Conclusions The regulatory effect of DEFSJ extract on anti-breast cancer involves the PI3k/Akt pathway,and the effect varies with phenotypic differences.

Objective To assess the 3-year anti-HBs persistence after primary vaccination with three-dose of hepatitis B vaccine (HepB) among normal and high-responder adults. Methods A total of 24 237 healthy adults who had no histories of hepatitis B infection and hepatitis B vaccination, resided in local areas for more than six months and were aged 18-49 years were selected from 79 villages of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling method. Each group was vaccinated with one of the following four types of HepB at 0-1-6 months schedule: 20 μg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20μg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10μg HepB-SC and 10 μg HepB derived in Hansenula polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). During the follow-up to normal and high-responders, the following information was collected: the demographic characteristic (including age and gender), histories of hepatitis B infection, hepatitis B vaccination, smoking, drinking and chronic diseases. Blood samples were collected one month (T1) and three years after primary vaccination (T2) and anti-HBs, anti-HBc and HBsAg (if anti-HBs<10 mU/ml) were detected by CMIA. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple logistic regression analysis and multifactor linear regression model analysis, respectively. Results A total of 4 677 normal and high-responders were identified. Among 4 677 participants, 2 014 (43.06%) were males and 2 663 (56.94%) were females. The positive rate was 100%at T1 and it decreased to 80.99% (3 788/4 677) three years after vaccination. The corresponding GMC was decreased from 1 413.48 (95%CI:1 358.86-1 470.30) mU/ml to 60.33 (95%CI:56.97-63.90) mU/ml. When comparing with those vaccinated 20 μg HepB-CHO, the significantly lower positive rate of anti-HBs three years after vaccination was observed in those vaccinated 20 μg HepB-SC, 10 μg HepB-SC and 10 μg HepB-HP. The OR (95%CI) was 0.65 (0.50-0.84), 0.52 (0.41-0.67) and 0.31 (0.28-0.45), respectively. The GMC of anti-HBs was also significantly lower among those vaccinated 20μg HepB-SC, 10μg HepB-SC and 10 μg HepB-HP. The b (95%CI) was -0.33 (-0.47- -0.20), -0.41 (-0.55- -0.28) and -0.78 (-0.92--0.65), respectively. The GMC of anti-HBs in those aged 30-39 years old and 40-49 years old were lower than that in 18-29 years. The b (95%CI) was-0.31 (-0.47--0.15) and-0.24 (-0.39--0.09), respectively. When comparing with those whose anti-HBs titer was less than 999 mU/ml at T1, the significantly higher positive rate of anti-HBs three years after vaccination was observed in those whose anti-HBs titer was 1 000-1 999 mU/ml, those whose anti-HBs titer was 2 000-9 999 mU/ml and those whose anti-HBs titer was ≥10 000 mU/ml. The OR (95%CI) was 4.97 (3.80-6.49), 7.87 (16.19-10.01) and 9.67 (6.47-14.44), respectively. When comparing with those whose anti-HBs titer was ≤999 mU/ml at T1, the GMC of anti-HBs three years after vaccination was also significantly higher among those whose anti-HBs titer at T1 was 1 000-1 999 mU/ml, those whose anti-HBs titer at T1 was 2 000-2 999 mU/ml and those whose anti-HBs titer at T1 was≥10 000 mU/ml. The b (95%CI) was 1.00 (0.87-1.14), 1.85 (1.74-1.97) and 3.28 (3.12-3.44), respectively. Four subjects showed HBsAg seroconversion and anti-HBc conversion rate was 4.68% at T2. Conclusions Anti-HBs GMC decreased rapidly three years after primary vaccination among normal and high-responder adults, while the positive rate of anti-HBs still kept at a high level. The anti-HBs persistence after primary vaccination was associated with HepB type, age and GMC of anti-HBs one month after vaccination.