Objective To explore the effects of the different concentrations of magnesium ions on vascular smooth muscle cell (VSMC) calcification in rats. Methods VSMCs were obtained from rat aortic, and were identified by immunocy-tochemistry. VSMCs were then randomly divided into control group, high phosphorus group and magnesium intervention group. VSMCs were cultured with 10%fetal bovine serum in control group. VSMCs were cultured with high phosphorus in high phosphorus group. VSMCs were cultured with different concentrations of magnesium chloride based on the high phos-phorus medium in magnesium intervention group (final concentrations of magnesium ions were 1, 2 and 3 mmol/L). The calci-um content and alkaline phosphatase(ALP)activity were measured after the stimulation for 7 days. The expression of Cbfα1 mRNA was detected by RT-PCR. Results Compared with control group, calcium deposits were found significantly higher in high phosphorus group and magnesium intervention group. The calcified nodules gradually reduced with the increased magnesium ion concentration in the intervention group. The calcium contents were significantly lower in the intervention groups (2 and 3 mmol/L) compared with those of high phosphorus group (P<0.05), but no difference was found between 1 mmol/L magnesium intervention group and high phosphorus group. There were no significant differences in the ALP activity and Cbfα1 mRNA expression between intervention groups (2 and 3 mmol/L) and control group (P<0.05). The ALP activity and the expression of Cbfα1 mRNA were gradually decreased with the increased magnesium ion concentration in the inter-vention group, and which were lower than those of high phosphorus group (P<0.05). Conclusion Magnesium can reduce calcification and osteoblastic transdifferentiation, which may be achieved by reducing the expression of Cbfα1 in VSMCs.

Objective:Summarize and analyze the clinical features of immune checkpoint inhibitor (ICI)-related colitis.Methods:From January 2019 to September 2020, the clinical data of 8 patients with ICI-related colitis from Peking Union Medical College Hospital were retrospectively collected and including the onset of ICI-related colitis, clinical symptoms, endoscopic and pathological findings, treatment, comorbidities and resuming of ICI. Independent sample t test was used for statistical analysis. Results:Eight patients were all male, and the median age (range) was 66 years old (55 to 74 years old), 7 cases were diagnosed with stage Ⅳ lung cancer and 1 case was diagnosed with stage Ⅲc pyelo-carcinoma. Among 8 patients, 4 cases of ICI-related colitis occurred during combination of anti-programmed death-1 (PD-1) treatment and chemotherapy, 2 cases occurred during anti-PD-1 monotherapy after combination of anti-PD-1 treatment and chemotherapy, and 2 cases occurred after anti-PD-1 monotherapy. The median time (range) was 44 d (27 to 128 d) from initial anti-PD-1 treatment to the onset of ICI-related colitis and the median time (range) was 8 d (6 to 35 d) from last anti-PD-1 treatment to onset of ICI-related colitis. The ICI efficacy of 4 patients had partial response, 2 patients had stable disease, 1 patient had disease progression, and 1 patient′s condition was not assessed. All 8 patients had moderate to severe extensive colitis. The main clinical manifestation was diarrhea (5/8), 3 patients accompanied by abdominal pain. The endoscopic findings were diffuse mucosal erosion, accompanied by ulcer in 2 patients. The main pathologic findings were cryptitis or crypt abscess, accompanied by apoptosis in 2 patients. Eight patients were all treated with glucocorticoids, among them 2 patients were further treated with biologics, due to the insufficient efficacy of glucocorticoid treatment, 4 patients had opportunistic infections. The initial prednisone dose for patients with opportunistic infections and patients without opportunistic infections was (85.00±52.60) and (60.00±23.09) mg, respectively. The prednisone treatment course was (8.75±4.03) and (7.50±3.11) weeks, respectively, and the differences were not statistically significant (both P>0.05). The colitis relapsed in all 3 patients after resuming of ICI. Conclusions:ICI-related colitis had corresponding ICI treatment history and clinical, endoscopic, and histopathological features. Glucocorticoid is the main treatment, and it is prone to relapse after resuming of ICI.

Objective Tumor size discrepancy in measurement between real-time ultrasonic elastography and conventional uItrasound(US) was found in some breast lesions.The study was designed to investigate the value of the feature in the diagnosis of breast cancer,and its relationship with the margin features on gray-scale US.Methods Both US and real-time elastogram using a Hitachi EUB-8500 US system were performed in 308 consecutive Datients.The margin features on US and the size measured on both methods were documented.A lesion was defined as a significant size discrepancy when a larger size measured at elastogram.Sensitivity,specificity,and overall accuracy of feature to diagnosis malignancy were determined by surgical pathology as gold standard.Results There were total 166 benign,163 malignant and 3 borderline lesions.of 99 lesions with larger measurement on elastography,there were 91 malignant lesions and 8 benign lesions.By the feature of size discrepancY,the sensitivity,specificity and accuracy was achieved 55.8%,96.9%,75.7%,respectively.The size measured on elastogram was statistically larger than that on gray scale US(t=-11.0,P＜0.05).The ratio of indistinct,angular and spiculated margin characteristics were significantly higher in breast cancers with larger size measurement than those with unchanged or decreased size measurement(P＜0.05).Conclusions The increased size-measurement at elastography is helpful to diagnosis breast cancers.And it is more likely to be present in breast cancers with indistinct,angular or spiculated margin.

Objective To investigate the effects and possible mechanisms of nicorandil on lung injury of the collapsed lung in one-lung ventilation.Methods Twenty-four clean Japanese big-ear rabbits were randomly divided into sham group (group S) (two-lung ventilation + thoracotomy),negative control group (group C) (one-lung ventilation + thoracotomy + saline),nicorandil group (group N) (one-lung ventilation+thoracotomy+nicorandil) and antagonist group (group J) (onelung ventilation+ thoracotomy+ nicorandil+ glyburide) equally.Mechanical ventilation was implemented through self-made double-lumen endotracheal tube after intravenous induction through ear marginal vein.Intravenous maintenance medicine was infused by trace injection pump after anesthesia induction.Thoracic surgery was simulated through one-lung or two-lung ventilation determined by auscultation,bubble test and direct observation.Then wet and dry weight ratio (W/D) and content of MDA were measured after non-ventilatory lung was processed and preserved.The expression of Akt,p-Akt and NF-κB protein in non-ventilatory lung tissue were detected by Western-blot in all groups.Results In respects of W/D and content of MDA,the other three groups had significant differences compared with group S (P ＜ 0.05).It was significantly lower in group N than in group C (P ＜0.05),and it was significantly higher in group J than in group N (P＜0.05).The expressions of pAkt protein and p-Akt/Akt in group N were significantly higher than those in group S and group C (P＜0.05).Those of group J were significantly lower than group N (P＜0.05).Compared with group S,the expression of NF-κB protein in group C was significantly higher (P＜0.05).That of group N was significantly lower than that of group C (P＜0.05).But that in group J was higher than that in group N (P ＜ 0.05).Conclusion Nicorandil has a protective effect on the collapse and inflation of non-ventilatory lung in rabbits under one-lung ventilation,acting on mitoKATP through PI3K/Akt,and down-regulating NF-κB to reduce IR-induced lung injury.

Objective:To analyze clinical characteristics and monitor microbiome changes in patients with anti-PD-1 associated colitis.Methods:Two patients with non-small cell lung cancer who developed colitis after treated with anti-PD-1 antibodies were retrospectively analyzed in Peking Union Medical College Hospital from January 2019 to January 2020. The clinical symptoms, endoscopic and pathological manifestations, as well microbiome changes were analyzed and compared during pre-treatment, post-treatment and relapse.Results:The main clinical manifestations included diarrhea, elevated inflammatory indicators, colonic mucosal diffuse hyperemic edema with erosion by endoscopy. Changes in the structure of crypts were common pathological characteristics. Glucocorticoids were effective agents, which achieved clinical remission and mucosal healing. The microbiome composition of OTUs was different. After glucocorticoid treatment, the alpha diversity Observed species, Shannon, Simpson, Chao1, ACE indexes all decreased. The Firmicutesdecreased with Bacteroidetesincreasing in phylum level; while the Bacteroides increased with Ruminococcaceaedecreasing in genus level. Lactobacilluswas the potentially beneficial genus. Conclusion:Patients developing anti-PD-1 associated colitis have characteristic clinical and pathological manifestations. Glucocorticoids are effective treatment. The fecal microbiome diversity, relative abundance of major phylum and genus have changed after treatment.

Objective:To investigate the effect and mechanism of short-chain fatty acids (SCFAs) on the side-effect of tacrolimus on blood glucose.Methods:The C57BL/6 mice were treated with tacrolimus orally (10 mg/kg, tacrolimus group), tacrolimus plus 150 mmol/L sodium butyrate and isovalerate mixed solution (SCFAs group), broad-spectrum antibiotics (antibiotic group), and tacrolimus plus broad-spectrum antibiotics (tac&abx group). After 8 weeks intervention, the fasting blood glucose (FBG), oral glucose tolerance test (OGTT), hemoglobin A1C (HbA1c) were tested as indicators of glucose metabolism, and the gut microbiota, SCFAs concentration in the ileocecal, serum glucagon-like peptide-1 (GLP-1), fasting serum insulin, and GLP-1 expression in intestinal mucosa were performed for intestinal-glucose metabolism mechanism.Results:The FBG and HbA1c were significantly increased in tacrolimus group[(7.31±0.97)mmol/L, (8.34±1.12)%] than control group [(5.23±0.30)mmol/L, (4.32±0.80)%, all P<0.05], which remained normal in antibiotic group [(4.92±0.31)mmol/L, (5.61±0.98)%)], tac&abx group[(5.95±0.37)mmol/L, (4.56±0.26)%] and SCFAs groups [(5.87±0.68)mmol/L, (5.07±1.79)%]. The OGTT in the tacrolimus group showed glucose tolerance impairment, while other groups remained normal. The ileocecal butyric acid and isovaleric acid concentrations in the tacrolimus group were (722.3±262.2) μg/g and (10.0±5.1)μg/g, lower than the control group[ (1 321.3±165.5) μg/g, (19.7±3.6)μg/g, P<0.05]. The above acids in the SCFAs group remained normal as in the control group [(1 375.7±451.6) μg/g, (24.5±11.5)μg/g)]. The fasting serum insulin in the tacrolimus group decreased significantly to (3.2 ± 0.6)mIU/L, compared with control[ (4.4±0.9) mIU/L]and SCFAs groups [(7.0±1.1) mIU/L]. The GLP-1 test indicated a significant decrease in the tacrolimus group[ (4.7±2.9)pg/ml, P<0.05] compared with the SCFAs group and control group [(42.5±19.9) pg/ml, (33.1±9.1) pg/ml]. Conclusions:Tacrolimus affects glucose metabolism through the SCFAs-associated GLP-1 pathway in the intestine, and oral supplementation with mixed SCFAs provides a new insight for the prevention and treatment of tacrolimus-induced hyperglycemia in transplant recipients.

OBJECTIVETo evaluate the accuracy and clinical significance of clinical complete response (cCR) after neoadjuvant themoradiotherapy for locally advanced rectal cancer.

METHODSLocally advanced rectal cancer patients who received neoadjuvant chemoradiotherapy following radical resection were retrospectively assessed for tumor response during 2005 to 2014 from the database of colorectal cancer. The concomitant preoperative chemoradiation consisted of 50 Gy radiation, fractionated within 5 weeks and 5-FU combined with oxaliplatin. Endorectal ultrasound and MRI were applied to preoperative staging, and postoperative gross pathologic inspection was retrospectively employed to evaluate the status of clinical complete response(cCR).

RESULTSA total of 227 patients undergoing radical surgery were enrolled in the study. Complete pathological response (ypT0N0, pCR) was found in 40 patients(17.6%) by postoperative pathologic examination while the rate of node involved in ypT0 patients was 11.1%. The preoperative rectal MRI was more sensitive to correlate ypT0 than endorectal ultrasound and gross pathologic inspection(60.0% vs 19.4% and 17.8%), but the accuracy and specificity showed no significant differences among these three tests. Multivariate Logistic regression analysis revealed preoperative MRI evaluation of cT0 might predict ypT0 independently(OR=4.975, 95% CI: 1.073 to 23.067, P=0.040).

CONCLUSIONIt is difficult to diagnose the primary tumor to be a cCR status based on preoperative MRI, EUS, or ulceration of rectal mucosa, and further to predict pCR. Preoperative MRI is more sensitive. The strategy of "wait and see" for cCR patients after neoadjuvant chemoradiation should be seriously considered in the decision-making before surgery.

Chemoradiotherapy ; Fluorouracil ; Humans ; Magnetic Resonance Imaging ; Neoadjuvant Therapy ; Neoplasm Staging ; Postoperative Period ; Preoperative Period ; Rectal Neoplasms ; Remission Induction ; Retrospective Studies ; Treatment Outcome

Objective:To explore the endoscopic features of early gastric cancer (EGC) related to non-curative endoscopic resection, and to construct an assessment model to quantify the risk of non-curative resection.Methods:From August 2006 to October 2019, 378 lesions that underwent endoscopic resection and were diagnosed pathological as EGC in the Department of Gastroenterology, Peking Union Medical College Hospital were included in this case-control study.Seventy-eight (20.6%) non-curative resection lesions were included in the observation group, and 234 lesions which selected from 300 lesions of curative resection were included in the control group according to the difference of operation year ±1 with the observation group, and the ratio of 1∶3 of the observation group to the control group. Univariate and multivariate logistic regression analysis were performed to explore the risk factors for non-curative resection. The independent risk factor with the minimum β coefficient was assigned 1 point, and the remaining factors were scored according to the ratio of their β coefficient to the minimum. A predictive model was established to analyze the 378 lesions.The non-curative resection rates of lesions of different scores were calculated. Results:Univariate analysis showed that the lesion diameter, the location, redness, ulcer or ulcer scar, fold interruption, fold entanglement, and invasion depth observed with endoscopic ultrasonography (EUS) were associated with non-curative resection of EGC lesions ( P<0.05), and contact or spontaneous bleeding may be associated with non-curative resection ( P=0.068). Multivariate logistic regression analysis showed that submucosal involvement (VS confined to the mucosa: β=0.901, P=0.011, OR=2.46, 95% CI: 1.23-4.92), lesion diameter of 3-<5 cm (VS <3 cm: β=0.723, P=0.038, OR=2.06, 95% CI: 1.04-4.09), lesion diameter of ≥5 cm (VS <3 cm: β=2.078, P=0.003, OR=7.99, 95% CI: 2.02-31.66), location in the upper 1/3 of the stomach (VS lower 1/3: β=1.540, P<0.001, OR=4.66, 95% CI: 2.30-9.45), and fold interruption ( β=2.287, P=0.008, OR=1.93, 95% CI: 0.95-3.93) were independent risk factors for non-curative resection of EGC lesions. The factor of lesion diameter of 3-<5 cm and submucosal involvement were assigned 1 point respectively, location in the upper 1/3 of the stomach was assigned 2 points, diameter of ≥5 cm and fold interruption were assigned 3 points respectively, and other factors were assigned 0 point. Then the analysis of 378 lesions showed that the probability of non-curative resection at ≥2 points was 41.9% (37/93), 4 times as much as that at 0 [11.5% (25/217)]. Conclusion:EGC lesions with diameter ≥3 cm, located in the upper 1/3 of the stomach, interrupted folds or submucosal involvement are highly related to non-curative resection. The predictive model based on these factors achieves satisfactory efficacy, but it still needs further validation in larger cohorts.

Objective:To investigate the clinicopathological characteristics and the risk factors of lymph node metastasis(LNM) of undifferentiated early gastric cancers(EGCs) in elderly patients.Methods:The elderly patients(≥65 years old) who underwent radical gastrectomy with lymph node dissection and were diagnosed as having EGCs in Peking Union Medical College Hospital from January 2010 to August 2019 were included. The clinicopathological characteristics of undifferentiated EGCs(namely signet ring cell EGCs and poorly differentiated EGCs) were compared with those of differentiated EGCs, and the risk factors for LNM of undifferentiated EGCs in the elderly patients were analyzed with logistic regression.Results:Data of 165 elderly EGCs patients were reviewed, including 82 undifferentiated EGCs (11 signet ring cell and 71 poorly differentiated) and 83 differentiated EGCs. The overall LNM incidence was 9.1% (15/165) in elderly EGCs patients, 4.8% (4/83) and 13.4% (11/82) in differentiated and undifferentiated EGCs, respectively. Of all undifferentiated EGCs, the LNM incidence in poorly differentiated EGCs was 15.5%(11/71), and none of 11 signet ring cell EGCs had LNM. Depth of tumor invasion( P=0.019), tumor size( P=0.006), combination of ulceration( P=0.006), depressed gross type( P=0.003) were found to be associated with LNM in elderly undifferentiated EGCs patients under univariate analysis. Multivariate analysis revealed that submucosal invasion( OR=11.98, 95% CI: 1.17-122.84, P=0.037) and tumor size >2 cm ( OR=11.95, 95% CI: 1.88-76.07, P=0.009) were independent risk factors for LNM in elderly undifferentiated EGCs patients. All elderly undifferentiated EGCs patients who met the criteria for expanded indications had no LNM. Conclusion:Submucosal invasion and tumor size >2 cm are independent risk factors for LNM in elderly undifferentiated EGCs patients. The elderly EGCs patients who met the criteria for expanded indications are suitable for endoscopic submucosal dissection.

Objective To clarify the clinical features of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) with minor endoscopic abnormalities. Methods The clinical data of 6 patients with MEITL characterized by minor endoscopic abnormalities in Peking Union Medical College Hospital from 2012 to 2016 were retrospectively analyzed, including clinical manifestations, endoscopic, pathological features, medications and prognosis. Results Five out of 6 patients were male, with an average age of 61.2 years old. The median disease duration was 4.5 months. All patients initially presented with diarrhea without specific findings for serologic testing. CT enterography showed continuous intestinal lesions, including symmetric thickening of the bowel wall, abnormal hyperenhancement of mucosal surface and lymphadenopathy. Endoscopic appearances were only mildly abnormal, including mucosal swelling, atrophy of villus, mosaic sign and shallow ulcers. Histopathologic findings revealed massive small to medium sized T lymphocytes infiltration with positive expression of CD3 and CD8. Chemotherapy and palliative treatment were administrated after diagnosis. Conclusions Clinical presentations of MEITL are non-specific with minor endoscopic abnormalities. Therefore, biopsy is indispensable for patients with a relatively normal endoscopic result.