Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Objective:To explore the selection of surgical methods for different sites of symptomatic Rathke's cleft cyst (RCC) and the clinical efficacies of these patients.Methods:Forty-seven patients with symptomatic RCC, admitted to our hospital from January 2016 to December 2019, were chosen in our study; 21 patients with intrasellar symptomatic RCC accepted surgery via unilateral nasal approach at the right side, 19 patients with intra-suprasellar symptomatic RCC accepted surgery via bilateral nasal approach, 3 patients with suprasellar symptomatic RCC accepted endonasal transsphenoidal surgery under endoscope, and 4 patients with suprasellar symptomatic RCC accepted craniotomy via pterion approach. The clinical efficacies and complications of patients accepted different surgical methods were compared. All patients were followed up for 3-36 months to observe the recurrence.Results:The postoperative symptoms of the patients were effectively improved, including headache relief ratio of 27/31, vision loss improvement ratio of 5/5, high prolactin relief ratio of 11/13, pituitary function improvement ratio of 9/18. Complications occurred in 6 patients, presenting as diabetes insipidus. Four patients recurred during follow-up.Conclusion:Intrasellar and intra-suprasellar symptomatic RCC accepted surgery via endoscopic transnasal transsphenoidal approach are safe and effective; selection of surgical methods for suprasellar symptomatic RCC should be determined according to the sizes and growth directions of cysts.

Objective To investigate the recurrence and risk factors of gastric high-grade intraepithelial neoplasia(HGIN)and early gastric cancer(EGC)after endoscopic submucosal dissection (ESD). Methods The clinical and follow-up data on 444 patients(451 lesion)with HGIN and EGC undergoing ESD in Digestive Endoscopy Center of Chinese PLA General Hospital from November 2006 to January 2016 were summarized, and the risk factors of recurrence were analyzed. Results A total of 410 patients were followed-up, and the recurrence rate was 3.2%(13 patients, 13 lesions), with mean recurrence time of 17.6±9.6 months(6-38 months). Univariate and multivariate analysis revealed that the size of the lesion>4.0 cm was the only risk factor of recurrence(P=0.012,OR=10.855,95%CI:1.673~70.442). Conclusion The rate of recurrence is increasing with the EGC extending, therefore, postoperative monitoring should be strengthened to patients with larger lesion.

Objective To assess the clinical value and safety of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for duodenal lesions.Methods The data of 12 patients with duodenal space-occupying lesions underwent EMR or ESD from January 2010 to December 2015 in Chinese PLA General Hospital were retrospectively analysed.Results All patients received operation, including 9 male and 3 female with mean age of 50.0 years(33.0-62.0 years).There were 8 lesions in duodenal bulb and 4 in descending part.The mean diameter of the lesions was 1.2 cm (0.5-3.0 cm).Three lesions were originated from mucosa, of which 2 were high-grade intraepithelial neoplasia and 1 was villous/tubular adenoma.Nine lesions were located in submucosa, including 3 cases of neuroendocrine neoplasm, 1 case of stromal tumor, 1 liomyoma case, 1 lipoma case, 1 case of Brunner glands adenoma, 1 case of ectopic pancreas, and 1 inflammatory lesion.One patient had perforation with rate of 8.3%(1/12) and was recovered after conserved treatment.The bleeding was very little during operation.No infection or stenosis happened.The mean hospitalized time was 6.0 days (1.0-12.0 days) after operation.No recurrence was found during 23.8 months(3.0-73.0 months) of follow-up.Conclusion EMR and ESD are effective and safe for treatment of duodenal space-occupying lesions.

Objective:To investigate ulinastatin (UTI) combined with Xingnaojing injection in the treatment of acute cerebral hemorrhage (ACH) and its effect on the serum high sensitivity C reactive protein (hs-CRP),D-dimer (D-D) and neuron specific enolase(NSE) levels.Methods:110 cases of ACH patients admitted in our hospital from January 2015 to December 2016 were selected and divided into two groups according to the random number table method.The control group was given UTI treatment,while the observation group was given UTI combined with Xingnaojing treatment.Then the brain edema absorption effect,NIHSS score,serum hs-CRP,D-D and NSE levels before and after the treatment of the two groups were recorded and compared;the safety ofmedicidstion of the two groups was evaluated.Results:At the 14th day after treatment,the total effective rate of cerebral hematoma absorption in the observation group was 89.1％,which was significantly higher than 67.3％ of the control group (P＜0.01).At the 14th day after treatment,the NIHSS scores of both groups were significantly lower than those before the treatment (P＜0.01);compared with that of the control group of the same time period,at the 14th day after treatment,the improvement effect of NIHSS score in the observation group was more significant (P＜0.01).Compared with those before the treatment,the serum hs-CRP,D-D and NSE levels of both groups at the 14th day after treatment were significantly decreased (P＜0.01);at the 14th day after treatment,the serum indicators of the observation group improved more significantly than those of the control group (P＜0.01).The incidence rate of adverse reaction in the observation group was 3.6％ compared with 5.5％ of the control group (P＞0.05).Conclusion:Ulinastatin combined with Xingnaojing Injection could rapidly relieve or eliminate hematoma in the treatment of acute cerebral hemorrhage,control the inflammatory response,improve the blood coagulation system and fibrinolytic system,protect the nerve cells and reduce the neurological damagee.

AIM:To investigate the effect of microRNA-429 (miR-429) on the expression of occludin (Ocln) in intestinal epithelial cells ( IECs) and intestinal epithelial barrier function in diabetic mice.METHODS:Diabetes mel-litus mouse model was induced by intraperitoneal injection of streptozocin.The expression of miR-429 in IECs of diabetic mice was inhibited by antagomiRNA-429 injected via tail vein.The expression of miR-429 and mRNA expression of Ocln were detected by real-time PCR.The protein expression of Ocln was determined by Western blotting and immunohistochem-istry.The urinary lactulose/mannitol ratio was measured by gas chromatography.The plasma LPS concentrations in the mice were measured by chromogenic end-point TAL kit.RESULTS:The results of real-time PCR confirmed that the ex-pression of miR-429 in IECs of diabetic mice was remarkably inhibited by tail-vein administration of antagomiRNA-429, and resumed to similar level of normal mice on the 6th day after the administration.After suppressing the level of miR-429, the expression of Ocln in IECs of diabetic mice increased significantly (P<0.05), while the urinary lactulose/mannitol ra-tio and the plasma LPS concentration decreased obviously ( P<0.05 ) .CONCLUSION:AntagomiRNA-429 effectively suppresses miR-429 expression in IECs of diabetic mice, and then enhances the expression of Ocln and partially resumes the intestinal epithelial barrier function.

AIM:To observe the inhibitory effect of siRNA targeting to Wip1 gene on the Wip1 gene expression in the colon cancer cells and to investigate the influence of Wip1 gene silencing on the chemotherapy sensitivity of colon cancer cells.METHODS:Wip1-811 siRNA targeting to Wip1 gene was transfected into RKO colon cancer cells with high expression of Wip1 gene.The mRNA expression of Wip1 was measured by real-time PCR.The protein level of Wip1 was detected by Western blotting.The viability of RKO colon cancer cells was measured by MTS assay.The cell apoptosis and cell cycle were analyzed by flow cytometry.RESULTS: Wip1-811 siRNA efficiently inhibited the expression of Wip1 at mRNA and protein levels.The enhanced chemotherapy sensitivity of RKO colon cancer cells was observed after inhibition of Wip1 gene expression.The viability of RKO colon cancer cells was decreased from (89.4 ±6.6)%to (74.7 ±3.9)%af-ter treated with 5-fluorouracil (P<0.05) and decreased from (77.9 ±2.4)%to (66.7 ±2.9)%after treated with oxali-platin ( P<0.05 ) .The cell apoptotic rate was increased from ( 7.7 ±0.5 )% to ( 12.3 ±3.2 )% and from ( 14.7 ± 2.1)% to (34.0 ±2.1)% when RKO colon cancer cells were treated with 5-fluorouracil and oxaliplatin, respectively (P<0.05).CONCLUSION:Wip1 gene silencing enhances chemotherapy sensitivity of colon cancer cells.

OBJECTIVETo investigate the effect and explore its possible mechanisms of epidermal growth factor receptor(EGFR) expression in macrophages on the anti-cancer effect of berberine (BER) on the growth of colorectal cancer.

METHODSMice with EGFR gene defects in macrophages (Egfr(fl/fl) LysM-Cre) and with EGFR gene expression in macrophages (LysM-Cre) (control group) were treated with azoxymethane (AOM) to establish colorectal tumor models. These models were treated with or without berberine (BER) intervention. The number of colorectal tumors and the gut length in the two groups were measured. The proliferation of tumor cells was detected by Ki-67 immunohistochemistry and apoptosis was detected by annexin V-FITC fluorescence labeling. Western blot was used to detect the expression of cleaved-caspase-3 protein.

RESULTSAfter treated with AOM, the colorectal tumor number was 10.26 ± 1.43 in the LysM-Cre group and 7.62 ± 1.05 in the Egfr(fl/fl) LysM-Cre group, showing a significant difference (P = 0.021). The gut length was (6.04 ± 1.06) cm in the LysM-Cre group and (6.39 ± 0.92) cm in the gfrfl/flLysM-Cre group, with a non-significant difference between the two groups (P = 0.075). After treated with AOM plus BER intervention, the colorectal tumor number of the LysM-Cre group was 8.35 ± 1.22 and that in the Egfr(fl/fl) LysM-Cre group was 2.66 ± 0.38, showing a very significant difference between the two groups (P = 0.006). The gut length of the LysM-Cre group was (7.34 ± 1.16) cm and that of the Egfr(fl/fl) LysM-Cre group was (10.01 ± 1.72) cm (P = 0.028). After treated with AOM, the ratio of Ki-67-positive tumor cells in the LysM-Cre group was (78.31 ± 3.43)% and that in the Egfr(fl/fl) LysM-Cre group was (75.85 ± 2.92)% (P = 0.282). After AOM plus BER treatment, the ratio of Ki-67-positive tumor cells in the LysM-Cre group was (42.43 ± 3.09)% and that in the Egfr(fl/fl) LysM-Cre group was significantly lower (29.65 ± 2.47)% (P = 0.018). The ratio of annexin V-positive tumor cells was (0.95 ± 0.13)% in the LysM-Cre group, not significantly different from (1.13 ± 0.16)% in the Egfr(fl/fl) LysM-Cre group (P = 0.175). After AOM plus BER treatment, the ratio of annexin V-positive tumor cells in the LysM-Cre group was (32.10 ± 1.97)%, significantly lower than the (47.08 ± 2.83)% in the Egfr(fl/fl) LysM-Cre group (P = 0.010). The level of cleaved-caspase-3 protein expression was 235.92 ± 19.73 in the Egfr(fl/fl) LysM-Cre group, significantly higher than the 119.71 ± 12.87 in the LysM-Cre group (P = 0.012).

CONCLUSIONSThe growth of colorectal cancer cells in mice can be inhibited by BER treatment, and this anti-cancer effect of BER can be further enhanced by EGFR gene knockout in macrophages. The mechanisms may be related to the inhibition of proliferation and promotion of apoptosis in colorectal cancer cells.

Animals ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Apoptosis ; Berberine ; pharmacology ; therapeutic use ; Caspase 3 ; Colorectal Neoplasms ; drug therapy ; Genes, erbB-1 ; physiology ; Immunohistochemistry ; Macrophages ; metabolism ; Mice

Objective To investigate the effect and explore its possible mechanisms of epidermal growth factor receptor(EGFR) expression in macrophages on the anti-cancer effect of berberine (BER) on the growth of colorectal cancer.Methods Mice with EGFR gene defects in macrophages ( Egfrfl/fl LysM-Cre) and with EGFR gene expression in macrophages ( LysM-Cre ) ( control group ) were treated with azoxymethane ( AOM ) to establish colorectal tumor models.These models were treated with or without berberine ( BER) intervention.The number of colorectal tumors and the gut length in the two groups were measured.The proliferation of tumor cells was detected by Ki-67 immunohistochemistry and apoptosis was detected by annexin V-FITC fluorescence labeling.Western blot was used to detect the expression of cleaved-caspase-3 protein.Results After treated with AOM, the colorectal tumor number was 10.26±1.43 in the LysM-Cre group and7 .62±1.05 in the Egfrfl/fl LysM-Cre group, showing a significant difference ( P=0.021) . The gut length was (6.04±1.06) cm in the LysM-Cre group and (6.39±0.92) cm in the gfrfl/flLysMC-re group, with a non-significant difference between the two groups ( P=00.75 ) .After treated with AOM plus BER intervention,the colorectal tumor number of the LysM -Cre group was 8.35±1.22 and that in the Egfrfl/fl LysM-Cre group was 2.66±0.38, showing a very significant difference between the two groups ( P=0.006) . The gut length of the LysM-Cre group was ( 7.34 ±1.16) cm and that of the Egfrfl/fl LysM-Cre group was (10 .01±1.72) cm ( P=0.028) .After treated with AOM, the ratio of Ki-67-positive tumor cells in the LysM-Cre group was (78.31±3.43)%and that in the Egfrfl/flLysM-Cre group was (75.85±2.92)%(P=0.282). After AOM plus BER treatment, the ratio of Ki-67-positive tumor cells in the LysM-Cre group was (42.43± 3.09)%and that in the Egfrfl/flLysM-Cre group was significantly lower (29.65±2.47)%(P=0.018).The ratio of annexin V-positive tumor cells was (0.95±0.13)%in the LysM-Cre group, not significantly different from (1.13±0.16)%in the Egfrfl/flLysM-Cre group (P=0.175).After AOM plus BER treatment, the ratio of annexin V-positive tumor cells in the LysM-Cre group was (32.10±1.97)%, significantly lower than the (47.08 ±2.83)% in the Egfrfl/fl LysM-Cre group ( P=0.010).The level of cleaved-caspase-3 protein expression was 235.92±19.73 in the Egfrfl/flLysM-Cre group, significantly higher than the 119.71±12.87 in the LysM-Cre group ( P=0.012 ) .Conclusions The growth of colorectal cancer cells in mice can be inhibited by BER treatment, and this anti-cancer effect of BER can be further enhanced by EGFR gene knockout in macrophages.The mechanisms may be related to the inhibition of proliferation and promotion of apoptosis in colorectal cancer cells.

Objective To investigate the effect and explore its possible mechanisms of epidermal growth factor receptor(EGFR) expression in macrophages on the anti-cancer effect of berberine (BER) on the growth of colorectal cancer.Methods Mice with EGFR gene defects in macrophages ( Egfrfl/fl LysM-Cre) and with EGFR gene expression in macrophages ( LysM-Cre ) ( control group ) were treated with azoxymethane ( AOM ) to establish colorectal tumor models.These models were treated with or without berberine ( BER) intervention.The number of colorectal tumors and the gut length in the two groups were measured.The proliferation of tumor cells was detected by Ki-67 immunohistochemistry and apoptosis was detected by annexin V-FITC fluorescence labeling.Western blot was used to detect the expression of cleaved-caspase-3 protein.Results After treated with AOM, the colorectal tumor number was 10.26±1.43 in the LysM-Cre group and7 .62±1.05 in the Egfrfl/fl LysM-Cre group, showing a significant difference ( P=0.021) . The gut length was (6.04±1.06) cm in the LysM-Cre group and (6.39±0.92) cm in the gfrfl/flLysMC-re group, with a non-significant difference between the two groups ( P=00.75 ) .After treated with AOM plus BER intervention,the colorectal tumor number of the LysM -Cre group was 8.35±1.22 and that in the Egfrfl/fl LysM-Cre group was 2.66±0.38, showing a very significant difference between the two groups ( P=0.006) . The gut length of the LysM-Cre group was ( 7.34 ±1.16) cm and that of the Egfrfl/fl LysM-Cre group was (10 .01±1.72) cm ( P=0.028) .After treated with AOM, the ratio of Ki-67-positive tumor cells in the LysM-Cre group was (78.31±3.43)%and that in the Egfrfl/flLysM-Cre group was (75.85±2.92)%(P=0.282). After AOM plus BER treatment, the ratio of Ki-67-positive tumor cells in the LysM-Cre group was (42.43± 3.09)%and that in the Egfrfl/flLysM-Cre group was significantly lower (29.65±2.47)%(P=0.018).The ratio of annexin V-positive tumor cells was (0.95±0.13)%in the LysM-Cre group, not significantly different from (1.13±0.16)%in the Egfrfl/flLysM-Cre group (P=0.175).After AOM plus BER treatment, the ratio of annexin V-positive tumor cells in the LysM-Cre group was (32.10±1.97)%, significantly lower than the (47.08 ±2.83)% in the Egfrfl/fl LysM-Cre group ( P=0.010).The level of cleaved-caspase-3 protein expression was 235.92±19.73 in the Egfrfl/flLysM-Cre group, significantly higher than the 119.71±12.87 in the LysM-Cre group ( P=0.012 ) .Conclusions The growth of colorectal cancer cells in mice can be inhibited by BER treatment, and this anti-cancer effect of BER can be further enhanced by EGFR gene knockout in macrophages.The mechanisms may be related to the inhibition of proliferation and promotion of apoptosis in colorectal cancer cells.