Assessing the genomic feature of Chinese patients with ampullary adenocarcinoma: potential therapeutic targets.

BACKGROUNDS: Ampullary adenocarcinoma (AMPAC) is a rare malignancy, treated as pancreatic or intestinal cancer based on its histologic subtype. Little is known about the genomic features of Chinese patients with AMPAC. MATERIALS AND METHODS: We enrolled 145 Chinese AMPAC patients in our local cohort and performed a compressive somatic and germline genetic testing using a 156 gene panel. Expression of PD-L1 (clone 28 - 8) was also assessed in tumor specimens from 64 patients. RESULTS: The frequency of genetic alterations (GAs) in Chinese patients with AMPAC was found to be distinctive, with TP53, KRAS, SMAD4, APC, CTNNB1, ARID1A, and CDKN2A emerged as the most frequently mutated genes. Comparing with Western patients, significant differences were observed in the prevalence of PIK3CA and ARID2. Furthermore, the incidence of MSI-H was lower in the Chinese cohort, with only two patients identified as MSI-H. Conversely, 11 patients (8.27%) had pathogenic/likely pathogenic germline alterations, all of which were in the DNA damage response (DDR) pathway. In our cohort, 34.48% (22/64) of patients exhibited positive PD-L1 expression in tumor cells, and this expression was associated with GAs in CTNNB1 and BLM. Importantly, over three-fourths of Chinese AMPAC patients in our study had at least one actionable GA, with more than one-fifth of them having actionable GAs classified as Level 3. These actionable GAs were primarily involved in the DDR and PI3K pathways. Notably, GAs in the DDR pathway were detected in both Chinese and Western patients, and regardless of their functional impact, these alterations demonstrated enhanced overall survival rates and higher tumor mutational burden (TMB) levels. CONCLUSION: These findings underscore the distinct genomic landscape of Chinese AMPAC patients and highlight the potential for targeted therapies based on the identified GAs.

Textbook outcome in gallbladder carcinoma after curative-intent resection: a 10-year retrospective single-center study / 中华医学杂志(英文版)

BACKGROUND@#Textbook outcome (TO) can guide decision-making among patients and clinicians during preoperative patient selection and postoperative quality improvement. We explored the factors associated with achieving a TO for gallbladder carcinoma (GBC) after curative-intent resection and analyzed the effect of adjuvant chemotherapy (ACT) on TO and non-TO patients.@*METHODS@#A total of 540 patients who underwent curative-intent resection for GBC at the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2020 were retrospectively analyzed. Multivariable logistic regression was used to investigate the factors associated with TO.@*RESULTS@#Among 540 patients with GBC who underwent curative-intent resection, 223 patients (41.3%) achieved a TO. The incidence of TO ranged from 19.0% to 51.0% across the study period, with a slightly increasing trend over the study period. The multivariate analysis showed that non-TO was an independent risk factor for prognosis among GBC patients after resection ( P = 0.003). Age ≤60 years ( P = 0.016), total bilirubin (TBIL) level ≤34.1 μmol/L ( P <0.001), well-differentiated tumor ( P = 0.008), no liver involvement ( P <0.001), and T1-2 stage disease ( P = 0.006) were independently associated with achieving a TO for GBC after resection. Before and after propensity score matching (PSM), the overall survival outcomes of non-TO GBC patients who received ACT and those who did not were statistically significant; ACT improved the prognosis of patients in the non-TO group ( P <0.05).@*CONCLUSION@#Achieving a TO is associated with a better long-term prognosis among GBC patients after curative-intent resection, and ACT can improve the prognosis of those with non-TO.

Prognostic value of using the preoperative serum fibrinogen to albumin ratio in gallbladder carcinoma patients after radical resection / 中华肝胆外科杂志

Objective:To investigate the prognostic value of using preoperative serum albumin-related biomarkers in gallbladder carcinoma (GBC) patients after resection.Methods:The clinical data of patients who underwent curative-intent resection for GBC at the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi’an Jiaotong University from January 2011 to December 2020 were retrospectively analyzed. Of 427 patients who were included in this study, there were 131 males and 296 females, aged (61.75±10.69) years old, range 30 to 87 years old. The 427 patients were divided into the training set ( n=300) and the testing set ( n=127). The training set was used to develop the nomogram model, and the testing set was used to evaluate its predictive ability. The X-Tile software was used to determine the best cut-off values for prognostic nutritional index (PNI), platelet to albumin ratio (PAR), fibrinogen to albumin ratio (FAR), and albumin to γ-glutamyl transpeptidase ratio (AGR). Based on the independent risk factors screened by the Cox proportional hazards regression model, the nomogram survival prediction model was developed by the rms installation package of the R software. The predictive ability of the nomogram was assessed by C-index and calibration curve. Results:The best cut-off values of PNI, PAR, FAR, and AGR were determined to be 44.0, 6.25×10 9/g, 0.08, and 2.03 g/U, respectively. FAR was better than PNI, PAR and AGR in predicting prognosis of patients after radical resection of GBC. Multivariate analysis showed that FAR>0.08 ( HR=2.124, 95% CI: 1.424-3.168), CEA>5.0 ng/ml ( HR=1.577, 95% CI: 1.047-2.375), CA-125>35.0 U/ml ( HR=1.454, 95% CI: 1.031-2.179), N1-2 stage ( HR=2.074, 95% CI: 1.420-3.029), major vascular invasion ( HR=3.292, 95% CI: 1.640-6.608), perineural infiltration ( HR=1.781, 95% CI: 1.045-3.034) and poor tumor differentiation ( HR=6.100, 95% CI: 2.753-13.515) were independent risk factors affecting prognosis of GBC after radical resection ( P<0.05). The C-index of the nomogram model was 0.790 (95% CI: 0.779-0.801) and 0.771 (95% CI: 0.754-0.788) in the training set and the testing set, respectively. Conclusion:Preoperative FAR had a good predictive ability for overall survival in patients with gallbladder carcinoma after radical resection, and it could be used for prognostic evaluation.

Overexpression of TRIM27 alleviates severe acute pancreatitis in mice by inhibiting NFκB/MAPK signaling pathway / 中华急诊医学杂志

Objective:To investigate the protective effect of overexpressed tripartite motif containing (TRIM27) on severe acute pancreatitis (SAP) in mice and its possible mechanism.Methods:Twenty-four mice were randomly divided into the sham operation + control virus group (AAV-GFP group), sham operation + overexpression of TRIM27 group (AAV-TRIM27 group), SAP + control virus group (SAP+AAV-GFP group), SAP + overexpression of TRIM27 group (SAP + AAV-TRIM27 group), with 6 mice in each group. SAP model of mice was established by intraperitoneal injection of L-arginine (4 mg/kg). The sham operation group was injected with equal volume of normal saline, and the virus group was injected with control or TRIM27 overexpression adeno-associated virus (2×10 11 μg/ per mice). The serum and pancreatic tissue samples were collected 72 h after modeling. The levels of serum amylase, lipase, tumor necrosis factor α (TNF-α), interleukin-1b (IL-1b), IL-6, macrophage chemoattractant protein-1 (MCP-1) and the expression of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) in pancreatic tissue were detected by enzyme-linked immunosorbent assay. Hematoxylin eosin staining was used to observe the pathological damage of pancreatic tissue. The expressions of myeloperoxidase (MPO) and Ly6g positive inflammatory cells in mouse pancreas were observed by immunohistochemistry. The expression of p-p65, p65, p-ASK1, ASK1, p-JNK, JNK, p-p38 and p38 in pancreatic tissue were detected by Western blot. Results:The expression of TRIM27 in pancreatic of mice was significantly down regulated after SAP ( P<0.05); after overexpression of TRIM27 by adeno-associated virus, the expression of TRIM27 in mouse pancreas was significantly up-regulated ( P<0.05). There was no significant difference in the indexes of mice between the AAV-GFP group and AAV-TRIM27 group ( P>0.05). Compared with the SAP + AAV-GFP group, the levels of serum amylase, lipase, TNF-α, IL-1b, IL-6 and MCP-1 in mice of the SAP + AAV-TRIM27 group were significantly decreased, MDA in pancreatic tissue was decreased, SOD and GSH were increased, MPO and Ly6g inflammatory cells were significantly decreased, and p-p65, p-ASK1, p-JNK, and p-p38 protein expression were down regulated. Conclusions:Overexpression of TRIM27 alleviates SAP in mice by inhibiting inflammatory response and oxidative stress, and its mechanism may be through inhibiting NFκB/MAPK signaling pathway.

Clinical diagnositic value of dynamic platelet and blood coagulation related indicators in acute pancreatitis / 中华急诊医学杂志

Objective:To investigate the predictive value of dynamic platelet and hemagglutination-related parameters in patients with acute pancreatitis (AP).Methods:The patients admitted to the Department of Emergency Surgery in the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2020 were analyzed. According to the inclusion criteria and exclusion criteria, patients with AP were retrospectively enrolled. According to the Chinese Guidelines for the Diagnosis and Treatment of Acute Pancreatitis (Shenyang, 2019), the patients were divided into two groups: severe acute pancreatitis (SAP group) and non-severe acute pancreatitis (non-SAP group) [including mild acute pancreatitis (MAP) and moderate severe acute pancreatitis (MSAP)]. A normal distribution of the maximum and mean aggregation rates of dynamic platelets (arachiidonic acid), plateletcrit (PCT) and bedside index for severity in acute pancreatitis (BISAP) scores and other measurement data were tested by t test, while measurement data of prothrombin time (PT), fibrinogen (FIB) and D-dimer that did not conform to normal distribution were tested by Mann-Whitney U test. χ 2 test was used for the counting data such as sex, age and etiology of patients in the two groups. The prognostic value of statistically significant indicators for non-SAP group and SAP group was further analyzed by receiver operating characteristic (ROC) curve. Results:A total of 146 patients with AP were enrolled, including 50 patients in SAP group and 96 in non-SAP group. The maximum and average aggregation rates of dynamic platelet (aracidonic acid) in the SAP group were (71.76±17.62) % and (67.91±18.10) %, PT (12.02±1.33) s, FIB (4.76±2.08) g/L, D-dimer (3.75±6.04) μg/L, PCT (0.23±0.08) %, and BISAP scores (1.42±1.18), which were all significantly higher than those in the non-SAP group [the maximum and average aggregation rates of dynamic platelet (arachiidonic acid) (46.65±20.11) % and (42.50±20.71) %, PT (11.50±1.51) s and FIB (3.91±1.48) g/L, D-dimer (1.00±1.37) μg/L, PCT (0.19±0.06) %, BISAP scores (0.45±0.66)] (all P<0.05). According to area under the ROC curve, the maximum and average aggregation rates of dynamic platelets (arachiidonic acid) in serum of patients with SAP were 0.83 and 0.82, respectively, and the sensitivities were 0.56 and 0.68, respectively. The specificity was 0.99 and 0.81, respectively, which was better than PT, FIB, D-dimer, PCT and BISAP scores in predicting the severity of AP. Conclusions:The maximum and average aggregation rates of dynamic platelets (arachidonic acid), PT, FIB, D-dimer, PCT and BISAP scores can be used as predictors of the severity of acute pancreatitis. The maximum and average aggregation rates of dynamic platelets (arachiidonic acid) were the best in predicting the severity of AP.

Exploration on the bioreduction mechanism of Cr(â ¥) by a gram-positive bacterium: Pseudochrobactrum saccharolyticum W1.

Bioremediation of chromium (Cr(Ⅵ)) contaminations has been widely reported, but the research on its removal mechanism is still scarce. Studies on Cr(Ⅵ) removal by strains affiliated to genus Pseudochobactrum revealed the Cr(Ⅵ) efficiency removal through the reduction of Cr(Ⅵ) to Cr(Ⅲ). However, the location of Cr(Ⅵ) reduction reaction and exact mechanism are still unspecified. In this work, a Gram-positive bacterial strain, Pseudochrobactrum saccharolyticum W1 (P. saccharolyticum W1) was isolated and tested to remove approximately 53.7% of Cr(Ⅵ) (initial concentration was 200 mg L-1) from the MSM medium. Analysis of SEM-EDS and TEM-EDS indicated that chromium-containing particles precipitated both on the cell surface and in the cytoplasm. Batch experiments indicated that the heat-treated bacterial cells almost had no ability to remove Cr(Ⅵ) from solution, while the resting cells could remove 62.0% of Cr(Ⅵ) at the initial concentration of 10 mg L-1. Additionally, at this concentration, 64.8% and 70.8% of Cr(Ⅵ) was reduced by cell envelope components and intracellular soluble substances after 6 h, respectively. These results suggested that the removal of Cr(Ⅵ) by P. saccharolyticum W1 was through direct reduction, which occurred on both cell envelop and cytoplasm. The results also showed that cytoplasm was the main site for Cr(Ⅵ) reduction compared to the cell envelop. Further analysis of FTIR and XPS verified that C-H, C-C, CO, C-OH and C-O-C groups of cells involved in correlation with chromium during Cr(Ⅵ) reduction. The study offered an insight into the Cr(VI) reduction mechanism of P. saccharolyticum W1.

Comparisons of clinical characteristics in patients with rosacea between Uygur and Han nationality in xinjiang / 中国医师杂志

Objective To explore the clinical characteristics of rosacea in Xinjiang.Methods From Jan 2013 to Jun 2015,clinical data of hospitalized patients who were diagnosed in the People's Hospital of Xinjiang Autonomous Region as rosacea were analyzed retrospectively.Results (1) The onset age of Uygur and Han were similar,while the incidence of Han was higher than Uygur in 41 ～ 50 age group.(2) The ratio of outdoors was higher in Uygur patients than Han patients.(3) Reactive erythema was the mainly feature in Han patients with obviously self-conscious symptoms including burning,drying,and tingling.The Uyghur patients were present with persistent erythema,papules and pustules;and had facial swelling and mild symptoms.(4) Positive rates of thyroid related antibodies and prolactin were higher in patients with rosacea.Conclusions The clinical features of rosacea are different between Uygur and Han nationalities in Xinjiang.